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Objective: Diabetes mellitus is a chronic metabolic disease often associated with hyperlipidemia. High low-density lipoprotein cholesterol (LDLc), high triglyceride, and low high-density lipoprotein cholesterol (HDLc) form the atherogenic lipoprotein profile. In this study, we examined how exenatide, a glucagon-like peptide 1 (GLP-1) analog, affects lipid profile and atherogenic indices in patients with diabetes. Methods: 100 patients diagnosed with type 2 diabetes mellitus (T2DM) participated in this retrospective study. Clinical and laboratory data of the patients were obtained before exenatide treatment and at the 12th week. From the lipid profile, Atherogenicity Plasma Index (AIP), Castelli Risk Index I (CRI-I), Castelli Risk Index II (CRI-II), Atherogenic Coefficient (AC), triglyceride (TG)/HDLc, TG- Glucose index (TyG) and TyG-Body Mass Index (BMI) data were calculated. Results: There was a significant improvement in body weight (BW), BMI, fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c), and conventional lipid profile after exenatide treatment. Statistically, significant decreases were observed in atherogenicity indices TyG index, TyG-BMI index, CRI-I, CRI-II, AIP, and AC indices (p < 0.05). This improvement in TG/HDLc, TyG index, CRI-I, CRI-II, AIP and AC indices was independent of HbA1c and BMI. Especially in patients with BMI ≥ 40 kg/m2, TyG-BMI index (p:0.01), a statistically significant decrease was observed in TyG index, TyG-BMI index, CRI-I, and AIP values in patients with HbA1c ≥8% (p:0.001, p:0.016, p:0.047, p:0.008). Conclusion: In addition to its commonly known effects such as lowering FPG levels and weight loss, exenatide has been observed to have a positive effect on traditional lipid profiles and atherogenicity-related indices. In addition to its antidiabetic effect, it should be considered in diabetic patients in treatment options for atherosclerotic cardiovascular prevention. [ABSTRACT FROM AUTHOR]

Background: Dyslipidemia is a crucial risk factor for atherosclerotic cardiovascular disease. However, there is limited data available on the differences in the prevalence of dyslipidemia between rural and urban populations in India. The aim of the present investigation is to describe the prevalence of dyslipidemia and the risk factors associated with adverse lipid profiles among adults residing in rural, sub-urban, and urban areas of India, and to assess its association with diabetes and hypertension. Methods: We enrolled adults over the age of 20 who lived in three distinct demographic areas in South India: rural, sub-urban, and urban. Data on demographics, lifestyle, disease history, family history, body weight, height, waist circumference, blood pressure, and clinical characteristics were collected for this study. We used chi-square tests and multivariable logistic regression to analyze demographic prevalence and risk factors related to lipid abnormalities among study participants. Results: This study enrolled 2976 randomly selected participants from rural, sub-urban, and urban communities in Tamil Nadu, India. Of these, 865 (29.1%) were rural residents, 1030 (34.6%) were sub-urban residents, and 1081 (36.3%) were urban residents. About 80% of women who lived in the suburban area had higher rates of low-HDL cholesterol. Compared to sub-urban (29.9%, 49%, and 21.1%) and rural (33.4%, 43.4%, and 24.1%) populations, urban populations had higher prevalence rates of hypercholesterolemia, hypertriglyceridemia, and elevated LDL-C (37.3%, 52.5%, and 38.6%), respectively. Men were more likely than women to develop dyslipidemia before the age of 40, but after that age, men showed a reduced risk of dyslipidemia than women, except for low HDL cholesterol. Age group, gender, current drinker, overweight, obesity, diabetes, and hypertension showed a significant association (p < 0.05) with dyslipidemia. Conclusions: The study found that more than 85% of the sub-urban and urban population had dyslipidemia (at least one lipid abnormality) compared to rural residents (78.5%). The prevalence rates were higher among those with diabetes and hypertension in urban residents. [ABSTRACT FROM AUTHOR]

Background: The aim of this study is to assess for the change in progression of inflammatory, adiposity, and atherosclerotic markers in first degree relatives of type 2 diabetes mellitus patients. Methods: Normal glucose tolerant (NGT) individuals (20–40 years) who had positive family history of T2DM (FHP) were enrolled in this prospective study based on ADA 2015 criteria. Age, sex, and BMI matched controls without any history of diabetes in their parents referred as family history negative (FHN) were taken for comparison. At baseline, detailed clinical assessment and requisite blood/imaging investigations were done. All the available subjects from the original cohort (FHN-32 and FHP-46) were studied after 2 years with recording of the clinical, biochemical and imaging parameters. Results: A total of 64 cases (FHP) and 42 controls (FHN) were enrolled at baseline. FHP group had significantly higher hsCRP (p = 0.039) and cIMT (p = 0.003) than that of FHN group. No significant difference in the rate of conversion of NGT to prediabetes (using multiple criteria) was found after 2 years between the two groups. cIMT was increased significantly from baseline in FHP group than FHN group at the end of the study(0.02 ± 0.03 vs. 0.01 ± 0.02 mm, p = 0.002). But there was no significant difference for changes in glycemic status, lipid parameters, HOMA IR, hsCRP, and adiposity markers between the two groups at the end of the study. Conclusion: Despite no significant differences in change in glycemic parameters or rates of conversion from NGT to pre diabetes, cIMT increased significantly in the normoglycemic offspring of T2DM subjects than those without history of T2DM in their parents. [ABSTRACT FROM AUTHOR]

Background: Metabolic syndrome (MetS) is a risk factor for prostate cancer (PCa) progression. Thus, this life-threatening disease demands a proactive treatment strategy. Andrographis paniculata (AP) is a promising candidate with various medicinal properties. However, the bioactivity of AP is influenced by its processing conditions especially the extraction solvent. Objective: In the present study, bioassay-guided screening technique was employed to identify the best AP extract in the management of MetS, PCa, and MetS-PCa co-disease in vitro. Methods: Five AP extracts by different solvent systems; APE1 (aqueous), APE2 (absolute methanol), APE3 (absolute ethanol), APE4 (40% methanol), and APE5 (60% ethanol) were screened through their phytochemical profile, in-vitro anti-cancer, anti-obese, and anti-hyperglycemic properties. The best extract was further tested for its potential in MetS-induced PCa progression. Results: APE2 contained the highest andrographolide (1.34 ± 0.05 mg/mL) and total phenolic content (8.85 ± 0.63 GAE/gDW). However, APE3 has the highest flavonoid content (11.52 ± 0.80 RE/gDW). APE2 was also a good scavenger of DPPH radicals (EC50 = 397.0 µg/mL). In cell-based assays, among all extracts, APE2 exhibited the highest antiproliferative activity (IC50 = 57.5 ± 11.8 µg/mL) on DU145 cancer cell line as well as on its migration activity. In in-vitro anti-obese study, all extracts significantly reduced lipid formation in 3T3-L1 cells. The highest insulin-sensitizing and -mimicking actions were exerted by both APE2 and APE3. Taken together, APE2 showed collectively good activity in the inhibition of PCa progression and MetS manifestation in vitro, compared to other extracts. Therefore, APE2 was further investigated for its potential to intervene DU145 progression induced with leptin (10–100 ng/mL) and adipocyte conditioned media (CM) (10% v/v). Interestingly, APE2 significantly diminished the progression of the cancer cell that has been pre-treated with leptin and CM through cell cycle arrest at S phase and induction of cell death. Conclusion: In conclusion, AP extracts rich with andrographolide has the potential to be used as an alternative to ameliorate PCa progression induced by factors highly expressed in MetS. [ABSTRACT FROM AUTHOR]

Background /purpose: Leptin—a protein hormone that plays vital role in the regulation of glucose homeostasis and insulin sensitivity, involved in regulating the circadian rhythms of gonadotropic, thyrotropic and adrenal axes in the endocrine system. This cross-sectional study was undertaken to correlate serum leptin levels and other demographic and biochemical parameters between prediabetic cases and control subjects of Kashmiri population. Furthermore, association of serum leptin levels with various demographic and biochemical parameters along with insulin resistance in pre-diabetic subjects was elucidated. In our study, pre-diabetic cases (n = 212) and healthy controls (n = 196) were enrolled. Methods: All study subjects underwent anthropometric assessment. Serum samples of all study subjects were analysed for biochemical parameters employing the principle of spectrophotometry and leptin levels using sandwich enzyme-linked immunosorbent assay (ELISA). Insulin levels of prediabetic cases were deduced by chemiluminescent micro particle immunoassay (CMIA) technology and thereby calculating their insulin resistance. Results: The cases had statistically increased leptin levels, lipid profile and obesity as compared to controls (p ≤ 0.05). Our study, showed a positive correlation between elevated leptin levels and increased lipid levels (total cholesterol, triglycerides; TG and very low density lipoproteins-cholesterol; VLDL-C) in prediabetics (p < 0.001). Conclusion: Beyond adiposity, leptin levels may increase the risk of pre-diabetes in Kashmiri population. Since the secretion, estimation and measurements of leptins are modest in contrast to insulin levels; therefore, leptin levels can also be included in the routine measurement as an indicator of metabolic syndrome and/or T2DM. [ABSTRACT FROM AUTHOR]

Blood eosinophil count is a useful measure in asthma or COPD management. Recent epidemiological studies revealed that body mass index (BMI) is positively associated with eosinophil counts. However, few studies focused on the role of adiposity and fatty acid-related metabolites on eosinophil counts, including the effect of genetic polymorphism. In this community-based study involving 8265 participants (30–74 year old) from Nagahama city, we investigated the relationship between eosinophil counts and serum levels of fatty acid-related metabolites. The role of MDC1, a gene that is related to eosinophil counts in our previous study and encodes a protein that is thought to be involved in the repair of deoxyribonucleic acid damage, was also examined taking into account its interaction with adiposity. Serum levels of linoleic acid (LA) and β-hydroxybutyric acid (BHB) were negatively associated with eosinophil counts after adjustment with various confounders; however, there were positive interactions between serum LA and BMI and between serum BHB and BMI/body fat percentages in terms of eosinophil counts. In never-smokers, there was positive interaction for eosinophil counts between the CC genotype of MDC1 rs4713354 and BMI/body fat percentages. In conclusion, both serum LA and BHB have negative impacts on eosinophil counts, while adiposity shows robust positive effects on eosinophil counts, partly via genetic background in never-smokers. [ABSTRACT FROM AUTHOR]

Internationally, studies have shown associations between lipids and glycemia; however, whether the link varies by gender and population has been rarely examined. We investigated relationships between glycemia and HDL- and Non-HDL-cholesterol and their modification by gender. We undertook a cross-sectional analysis from the National Health Examination Survey for Thailand (NHES-Thailand) and the Health Survey for England (HS-England) in adults aged 18–75 year. Glycaemia was assessed by FPG in Thailand and by HbA1c in the UK. In population- and gender-stratified analyses, the relationships between glycemia and lipids were explored. A total of 15,145 Thai and 3484 UK adults with blood measurement were included. The prevalences of prediabetes were: in NHES-Thailand, 16% (SE = 0.004), based on FPG (5.6 to < 7.0 mmol/L) and in HS-England, 19% (0.007) based on HbA1c (39 to < 48 mmol/mol). Increasingly abnormal glucose homeostasis was associated with increasing age, adiposity, SBP, proportion of antihypertensive and lipid-lowering agent use and with decreasing HDL-cholesterol. Independent of age, adiposity, smoking, alcohol, physical activity, and lipid and BP lowering drug use, increasing glycemia was associated with decreasing HDL-cholesterol specifically in women with prediabetes (NHES-Thailand, beta-coefficient − 0.07 (95% CI − 0.15, − 0.001) p = 0.04 and HS-England, − 0.03 (− 0.04, − 0.006) p = 0.01). In both populations, among those with prediabetes, increasing glycaemia is associated with an adverse, significant decline in HDL cholesterol, specifically in women. These adverse effects are apparent in widely-differing international populations. [ABSTRACT FROM AUTHOR]

SUGCT (C7orf10) is a mitochondrial enzyme that synthesizes glutaryl-CoA from glutarate in tryptophan and lysine catabolism, but it has not been studied in vivo. Although mutations in Sugct lead to Glutaric Aciduria Type 3 disease in humans, patients remain largely asymptomatic despite high levels of glutarate in the urine. To study the disease mechanism, we generated SugctKO mice and uncovered imbalanced lipid and acylcarnitine metabolism in kidney in addition to changes in the gut microbiome. After SugctKO mice were treated with antibiotics, metabolites were comparable to WT, indicating that the microbiome affects metabolism in SugctKO mice. SUGCT loss of function contributes to gut microbiota dysbiosis, leading to age-dependent pathological changes in kidney, liver, and adipose tissue. This is associated with an obesity-related phenotype that is accompanied by lipid accumulation in kidney and liver, as well as "crown-like" structures in adipocytes. Furthermore, we show that the SugctKO kidney pathology is accelerated and exacerbated by a high-lysine diet. Our study highlights the importance of non-essential genes with no readily detectable early phenotype, but with substantial contributions to the development of age-related pathologies, which result from an interplay between genetic background, microbiome, and diet in the health of mammals. [ABSTRACT FROM AUTHOR]

Background: Polycystic ovary syndrome (PCOS) is a frequent medical condition characterized by both metabolic and reproductive disorders. Different pharmaceutical treatments have been proposed for PCOS. However, side effects of long-term treatments and their probable low efficacy have made complementary and alternative treatments a valuable option. Recent reports have indicated the increased use of complementary treatments. Herbal medicine, as part of complementary medicine, was find introduced in traditional Persian and Chinese medicine. Medicinal herbs have used for a long time in the treatment of gynecological and infertility problems of PCOS patients. In this study, we aimed to review herbal medicines used for PCOS worldwide. Methods: PubMed, Embase, Cochrane, and Scopus databases were searched for clinical trials and Randomized Controlled Trials based on related keywords. Data were collected from 1990 to 2019. Results: According to a multitude of studies, a wide spectrum of herbs can be used to improve various aspects of PCOS. Herbs such as Cinnamomum verum, Trigonella foenum-graecum L., and Vitex agnus-castus can impact on menstrual and ovulatory dysfunctions, obesity, insulin resistance, lipid-metabolism dysfunction, and androgen excess-related conditions. Conclusion: Some plants as natural remedies may have beneficial effects on improving different aspects of PCOS; but further studies are needed to investigate their mechanisms and safety. [ABSTRACT FROM AUTHOR]

Objective: To study the location and expression of receptors (SR-BI/CLA-1, SR-BII, and LDLr) and transporter (ABCA1) involved in uptake and efflux of cholesterol in human spermatozoa and assess whether obesity alters its location/expression and whether this could be related to infertility. Design: Observational study. Setting: None Patient(s): Ten controls and 20 obese patients. Intervention(s): Anthropometric parameters. Serum and semen samples were collected. Main outcome measure(s): Spermatozoon concentration, immunolocalization, and protein expression in semen. Results: Spermatozoon concentration and motility was decreased in morbidly obese patients. SR-BI/CLA-1, SR-BII, LDLr, and ABCA1 are located in the spermatozoon cell membrane and the localization does not change between obese patients and controls. Control spermatozoa showed high SR-BI expression, and less expression for the rest of the receptors analyzed, indicating that SR-BI/CLA-1 is relevant in human spermatozoon cholesterol uptake/efflux. On the contrary, spermatozoa of obese patients showed less SR-BI/CLA-1 expression than controls, and more intense positive staining for SR-BII, LDLr, and ABCA1. Finally, human sperm expresses the 130- and 82-kDa hormone-sensitive lipase (HSL) isoforms. The 130-kDa isoform is expressed in the control sperm, and the expression disappears in the obese patients. Conclusion(s): The presence of lipid receptors/transporters and HSL in human spermatozoa suggests their role in the process of maturation/capacitation. The changes in the expression of lipid receptors/transporters and the lack of the 130-kDa HSL isoform in obese patients prevent the hydrolysis of cholesterol esters internalized by these receptors, and favor their accumulation in the cytoplasm of the spermatozoa that could contribute to lipotoxicity and infertility. [ABSTRACT FROM AUTHOR]

The places where a child lives and attends to school are both major environmental and social determinants of its present and future health status. Noncommunicable diseases (NCDs) and some of their risk factors among child and adolescent populations are obesity and dyslipidemia, so finding the patterns of distribution of these risk factors by gender, type of school, area, and margination level is important to do health intervention focusing in their necessities to prevent diseases at younger ages. Because of that, a cross-sectional study was performed among elementary and junior high school students from public and private schools in six of the seven areas of the metropolitan zone of San Luis Potosi, Mexico. Biochemical dyslipidemia indicators (triglycerides, total cholesterol, and high-density lipoprotein) and anthropometric data (weight and height) were obtained. Seventeen public schools and five private schools with a total of 383 students were included. More than half of the studied population (53.0%) had elevated triglyceride levels. A total of 330 students (86.2%) had normal levels of total cholesterol with a mean value of 141.7 mg/dl, and 202 schoolchildren (52.8%) had lower than acceptable levels of high-density lipoprotein (HDL) with a mean value of 43.9 mg/dl. There were differences in the levels of high-density protein between the areas and the type of school where they had been studied. Finally, a total of 150 students (39.4%) had at least one altered lipid value and 103 participants (26.9%) had two altered values. Several students, despite their young age, showed a high prevalence of risk factors, so it is important to design programs according to their necessities. [ABSTRACT FROM AUTHOR]

Sexual dimorphism in adiposity is well described in adults, but the age at which differences first manifest is uncertain. Using a prospective cohort, we describe longitudinal changes in directly measured adiposity and intrahepatocellular lipid (IHCL) in relation to sex in healthy term infants. At median ages of 13 and 63 days, infants underwent quantification of adipose tissue depots by whole-body magnetic resonance imaging and measurement of IHCL by in vivo proton magnetic resonance spectroscopy. Longitudinal data were obtained from 70 infants (40 boys and 30 girls). In the neonatal period girls are more adipose in relation to body size than boys. At follow-up (median age 63 days), girls remained significantly more adipose. The greater relative adiposity that characterises girls is explained by more subcutaneous adipose tissue and this becomes increasingly apparent by follow-up. No significant sex differences were seen in IHCL. Sex-specific differences in infant adipose tissue distribution are in keeping with those described in later life, and suggest that sexual dimorphism in adiposity is established in early infancy. [ABSTRACT FROM AUTHOR]

Beige adipocytes in white adipose tissue (WAT) are similar to classical brown adipocytes in that they can burn lipids to produce heat. Thus, an increase in beige adipocyte content in WAT browning would raise energy expenditure and reduce adiposity. Here we report that adipose-specific inactivation of Notch1 or its signaling mediator Rbpj in mice results in browning of WAT and elevated expression of uncoupling protein 1 (Ucp1), a key regulator of thermogenesis. Consequently, as compared to wild-type mice, Notch mutants exhibit elevated energy expenditure, better glucose tolerance and improved insulin sensitivity and are more resistant to high fat diet-induced obesity. By contrast, adipose-specific activation of Notch1 leads to the opposite phenotypes. At the molecular level, constitutive activation of Notch signaling inhibits, whereas Notch inhibition induces, Ppargc1a and Prdm16 transcription in white adipocytes. Notably, pharmacological inhibition of Notch signaling in obese mice ameliorates obesity, reduces blood glucose and increases Ucp1 expression in white fat. Therefore, Notch signaling may be therapeutically targeted to treat obesity and type 2 diabetes. [ABSTRACT FROM AUTHOR]

Lipids in skeletal muscle play a fundamental role both in normal muscle metabolism and in disease states. Skeletal muscle lipid accumulation is associated with several chronic metabolic disorders, including obesity, insulin resistance, and type 2 diabetes. However, it is poorly understood whether the lipid composition of skeletal muscle changes by contraction, due to the complexity of lipid molecular species. In this study, we used matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) to investigate changes in skeletal muscle lipid composition induced by contraction. We successfully observed the reduction of diacylglycerol and triacylglycerol, which are generally associated with muscle contraction. Interestingly, we found the accumulation of some saturated and mono-unsaturated fatty acids and poly-unsaturated fatty acids containing phosphatidylcholine in contracted muscles. Moreover, the distributions of several types of lipid were changed by contraction. Our results show that changes in the lipid amount, lipid composition, and energy metabolic activity can be evaluated in each local spot of cells and tissues at the same time using MALDI-IMS. In conclusion, MALDI-IMS is a powerful tool for studying lipid changes associated with contractions. [ABSTRACT FROM AUTHOR]

Dyslipidemia has been reported as a risk factor for incident hypertension in a few prospective studies, however, no study has specifically assessed different lipid measures including the lipid ratios, that is, total cholesterol (TC)/high-density lipoprotein cholesterol (HDL-C) and triglycerides (TGs)/HDL-C as predictors of hypertension among Middle Eastern women with high prevalences of dyslipidemia and hypertension. The study population consisted of 2831 non-hypertensive women, aged 20 years. We measured lipoproteins, and calculated non-HDL-C and the lipid ratios. The risk-factor-adjusted odds ratios for incident hypertension were calculated for every 1 standard deviation (s.d.) change in TC, log-transformed TG, HDL-C, non-HDL-C, TC/HDL-C and log-transformed TG/HDL-C using multivariate logistic regression analysis. Over a mean follow-up of 6.4 years, 397 women developed hypertension. An increase of 1 s.d. in TG, TC/HDL-C and TG/HDL-C increased the risk of incident hypertension by 16, 19 and 18%, respectively, and 1 s.d. increase in HDL-C decreased the risk of hypertension by 14% in the multivariable model (all P0.05). In models excluding women with diabetes and central or general obesity, TG, TG/HDL-C and TC/HDL-C remained as independent predictors of incident hypertension. In conclusion, dyslipidemia, using serum TG and TG/HDL-C, in particular, may be useful in identification of women at risk of hypertension, even in those without diabetes and central or general obesity. [ABSTRACT FROM AUTHOR]

Background/objectives:Takeaway food consumption is positively associated with adiposity. Little is known about the associations with other cardio-metabolic risk factors. This study aimed to determine whether takeaway food consumption is associated with fasting glucose, insulin, lipids, homeostasis model assessment (HOMA) and blood pressure.Subjects/methods:A national sample of 1896, 26-36 year olds completed a questionnaire on socio-demographics, takeaway food consumption, physical activity and sedentary behaviour. Waist circumference and blood pressure were measured, and a fasting blood sample was taken. For this analysis, takeaway food consumption was dichotomised to once a week or less and twice a week or more. Linear regression was used to calculate differences in the adjusted mean values for fasting lipids, glucose, insulin, HOMA and blood pressure. Models were adjusted for age, employment status, leisure time physical activity and TV viewing.Results:Compared with women who ate takeaway once a week or less, women who ate takeaway twice a week or more had significantly higher adjusted mean fasting glucose (4.82 vs 4.88 mmol/l, respectively; P=0.045), higher HOMA scores (1.27 vs 1.40, respectively, P=0.034) and tended to have a higher mean fasting insulin (5.95 vs 6.45 mU/l, respectively, P=0.054). Similar associations were observed for men for fasting insulin and HOMA score, but the differences were not statistically significant. For both women and men adjustment for waist circumference attenuated the associations.Conclusion:Consuming takeaway food at least twice a week was associated with cardio-metabolic risk factors in women but less so in men. The effect of takeaway food consumption was attenuated when adjusted for obesity. [ABSTRACT FROM AUTHOR]

The endoplasmic reticulum (ER) is the main site of protein and lipid synthesis, membrane biogenesis, xenobiotic detoxification and cellular calcium storage, and perturbation of ER homeostasis leads to stress and the activation of the unfolded protein response. Chronic activation of ER stress has been shown to have an important role in the development of insulin resistance and diabetes in obesity. However, the mechanisms that lead to chronic ER stress in a metabolic context in general, and in obesity in particular, are not understood. Here we comparatively examined the proteomic and lipidomic landscape of hepatic ER purified from lean and obese mice to explore the mechanisms of chronic ER stress in obesity. We found suppression of protein but stimulation of lipid synthesis in the obese ER without significant alterations in chaperone content. Alterations in ER fatty acid and lipid composition result in the inhibition of sarco/endoplasmic reticulum calcium ATPase (SERCA) activity and ER stress. Correcting the obesity-induced alteration of ER phospholipid composition or hepatic Serca overexpression in vivo both reduced chronic ER stress and improved glucose homeostasis. Hence, we established that abnormal lipid and calcium metabolism are important contributors to hepatic ER stress in obesity. [ABSTRACT FROM AUTHOR]

Objective:Mice from a long-term selective breeding experiment for high voluntary wheel running offer a unique model to examine the contributions of genetic and environmental factors in determining the aspects of behavior and metabolism relevant to body-weight regulation and obesity. Starting with generation 16 and continuing through to generation 52, mice from the four replicate high runner (HR) lines have run 2.5–3-fold more revolutions per day as compared with four non-selected control (C) lines, but the nature of this apparent selection limit is not understood. We hypothesized that it might involve the availability of dietary lipids.Methods:Wheel running, food consumption (Teklad Rodent Diet (W) 8604, 14% kJ from fat; or Harlan Teklad TD.88137 Western Diet (WD), 42% kJ from fat) and body mass were measured over 1–2-week intervals in 100 males for 2 months starting 3 days after weaning.Results:WD was obesogenic for both HR and C, significantly increasing both body mass and retroperitoneal fat pad mass, the latter even when controlling statistically for wheel-running distance and caloric intake. The HR mice had significantly less fat than C mice, explainable statistically by their greater running distance. On adjusting for body mass, HR mice showed higher caloric intake than C mice, also explainable by their higher running. Accounting for body mass and running, WD initially caused increased caloric intake in both HR and C, but this effect was reversed during the last four weeks of the study. Western diet had little or no effect on wheel running in C mice, but increased revolutions per day by as much as 75% in HR mice, mainly through increased time spent running.Conclusion:The remarkable stimulation of wheel running by WD in HR mice may involve fuel usage during prolonged endurance exercise and/or direct behavioral effects on motivation. Their unique behavioral responses to WD may render HR mice an important model for understanding the control of voluntary activity levels. [ABSTRACT FROM AUTHOR]

Background:LIGHT (lymphotoxin-like inducible protein that competes with glycoprotein D for herpesvirus entry on T cells) is a member of the tumor necrosis factor (TNF) family, primarily expressed in lymphocytes, which was associated with the induction of pro-inflammatory cytokines and alterations of lipid homeostasis in animal models. We aimed to analyze whether LIGHT has a role in the human obesity-associated inflammatory status.Methods:The association between circulating LIGHT concentrations and clinical variables was studied in 190 subjects with different degrees of obesity and glucose tolerance. The expression and release of 21 different cytokines, and the expression of genes involved in lipid metabolism were also evaluated after stimulation with LIGHT in cultured human differentiated adipocytes.Results:Serum LIGHT concentrations positively associated with body mass index (BMI), fat mass, glycated hemoglobin and fasting triglycerides, and negatively with high-density lipoprotein cholesterol. Circulating LIGHT concentrations were significantly increased in morbidly obese subjects and in patients with type 2 diabetes. LIGHT induced the secretion of several cytokines and upregulated the expression and secretion of interleukin-6 (IL-6), IL-8, Growth Regulated Oncogene (GRO) and monocyte chemotactic protein-1 (MCP-1). These observations were concomitant with the activation of nuclear factor (NF)-κB signalling in human differentiated adipocytes. LIGHT also upregulated the expression and synthesis of its own receptor (herpesvirus entry mediator (HVEM)) and decreased the expression of peroxisome proliferator-activated receptor-γ (PPAR-γ) and fatty acid synthase.Conclusion:These data suggest that LIGHT may have a role in mediating chronic inflammation and alterations of lipid metabolism in obese subjects. [ABSTRACT FROM AUTHOR]

Objective:The immediate cause of obesity is the massive deposition of subcutaneous and visceral fat attributing to the continuous proliferation and differentiation of preadipocytes. The identification of the underlying molecular mechanisms of preadipocytes differentiation is urgent, and will have an important role in plastic and reconstructive surgical procedures.Methods:Two small hairpin RNA (shRNA)-mediated RNA interference plasmids have been constructed on the basis of the activity of H1 promoter-driven expression vector psiRNA-hH1neo to suppress the expression of angiotensinogen (AGT) in human preadipocytes-visceral (HPA-v). Subsequently, glycerol-3-phosphate dehydrogenase (G3PDH) activity and intracytoplasmic lipids content were detected during the process of HPA-v differentiation.Results:Small hairpin RNA-expressing vectors have been successfully constructed to suppress the expression of AGT significantly. Both intracytoplasmic lipids content and G3PDH activity decreased to a certain extent compared with that in the control group in the whole process of HPA-v differentiation.Conclusions:Two shRNA-mediated AGT-targeting plasmids inhibited the process of HPA-v differentiation to a certain extent. However, the accumulation of intracytoplasmic lipids was not exclusively determined by the expression of AGT, and it may also be regulated by other factors. In conclusion, this study provided a method to inhibit the process of preadipocytes differentiation, and it may have a role in obesity treatment and adipose tissue engineering application. [ABSTRACT FROM AUTHOR]

Background/Objectives:To investigate the relationships between body mass index (BMI), body fatness, ethnicity, age and blood lipids.Subjects/Method:In a subsample (N=643) of the 2002 New Zealand Child Nutrition Survey (N=3275, age 5–14 years) consisting Māori (89 boys, 69 girls), Pacific (154 boys, 194 girls) and European (71 boys, 66 girls) ethnic groups, fat-free mass (FFM) was determined by bioimpedance analysis. FFM index (FFMI, FFM/height2), fat mass index (FMI, fat mass/height2) and percentage body fat (%BF) were derived. Plasma total cholesterol and high-density lipoprotein (HDL) cholesterol were measured in 515 (80%) of these children.Results:For the same BMI, %BF was lower in Pacific Island (P<0.0001) and Māori (P<0.0001) girls compared with European but for boys there were no ethnic differences. Cross-sectional analysis across ages using Hattori charts clearly showed sexual dimorphism with girls having a higher FMI, FFMI and BMI than boys by the age of 13 year. Both Pacific girls and boys showed upward trends in FFMI and FMI with age that were significantly higher than those of the other ethnicities. Adjusting for age, sex and ethnicity, %BF was a better predictor (R2=0.090, P=0.0002) of total cholesterol than BMI (R2=0.061, P=0.049) or waist (R2=0.075, P=0.013) while FFMI was the best predictor of HDL cholesterol (R2=0.15, P<0.0001) and waist was the best predictor of the total cholesterol/HDL cholesterol ratio (R2=0.17, P<0.0001).Conclusions:Measurements of body fat and indices of body fatness additional to BMI in multiethnic paediatric populations allow changes in fat mass and FFM to be tracked and improve the ability to predict dyslipidaemia.European Journal of Clinical Nutrition (2009) 63, 627–633; doi:10.1038/ejcn.2008.15; published online 27 February 2008 [ABSTRACT FROM AUTHOR]

Objectives:The orexigenic hormone ghrelin circulates mainly in two forms, acylated and desacyl ghrelin. We evaluated the impact of obesity and obesity-associated type 2 diabetes (T2D) on ghrelin forms and the potential role of acylated and desacyl ghrelin in the control of adipogenesis in humans.Methods:Plasma concentrations of the different ghrelin forms were measured in 80 subjects. The expression of the ghrelin receptor (growth hormone secretagogue receptor, GHS-R) was analyzed in omental adipose tissue using western blot and immunohistochemistry, and the effect of acylated ghrelin and desacyl ghrelin (0.1–1000 pmol l−1) on adipogenesis was determined in vitro in omental adipocytes.Results:Circulating concentrations of acylated ghrelin were increased, whereas desacyl ghrelin levels were decreased, in obesity and obesity-associated T2D. Body mass index, waist circumference, insulin and HOMA (homeostasis model assessment) index were positively correlated with acylated ghrelin levels. Obese individuals showed a lower protein expression of GHS-R in omental adipose tissue. In differentiating omental adipocytes, incubation with both acylated and desacyl ghrelin significantly increased PPARγ (peroxisome proliferator-activated receptor γ) and SREBP1 (sterol-regulatory element binding protein-1) mRNA levels, as well as several fat storage-related proteins, including acetyl-CoA carboxylase, fatty acid synthase, lipoprotein lipase and perilipin. Consequently, both the ghrelin forms stimulated intracytoplasmatic lipid accumulation.Conclusions:Both acylated and desacyl ghrelin stimulate lipid accumulation in human visceral adipocytes. Given the lipogenic effect of acylated ghrelin on visceral adipocytes, the herein-reported elevation of its circulating concentrations in obese individuals may play a role in excessive fat accumulation in obesity.International Journal of Obesity (2009) 33, 541–552; doi:10.1038/ijo.2009.40; published online 24 February 2009 [ABSTRACT FROM AUTHOR]

Objective:The severity of obesity is often more determined by the distribution of fat depots rather than by body weight itself. Therefore, the effect of rimonabant on fat distribution pattern was investigated in female candy-fed Wistar rats.Design:Female Wistar rats were fed a high fat, high carbohydrate (candy-) diet for 12 weeks. During the last 6 weeks rats were treated with rimonabant. Food intake and body weight development were investigated, as well as effects on total body fat, especially visceral fat and ectopic lipid accumulation in skeletal muscle and liver, determined by in vivo magnetic resonance imaging/magnetic resonance spectroscopy.Results:Candy-diet increased body weight, which was predominantly due to the increased total fat mass with predominance of visceral fat accumulation. Treatment with rimonabant fully reversed the weight gain and fat deposition in the visceral cavity and skeletal muscle, in contrast to pair feeding. In spite of an only transient reduction of food intake, body weight reduction, as well as normalized body fat, reduced visceral fat and intramyocellular lipids were maintained over the treatment period.Conclusions:We conclude that additional factors other than reduced caloric intake must be responsible for the improvements in these lipid parameters. The complete cluster of results is consistent with increased lipid oxidation caused by rimonabant.International Journal of Obesity (2008) 32, 1363–1372; doi:10.1038/ijo.2008.105; published online 15 July 2008 [ABSTRACT FROM AUTHOR]

Background:High-intensity progressive resistance training (PRT) improves adiposity and metabolic risk in adults, but has not been investigated in children within a randomized controlled trial (RCT).Objective:We hypothesized that high-intensity PRT (8 weeks, twice a week) would decrease central adiposity in children, as assessed via waist circumference.Methods Design/Setting/Participants:Concealed randomization stratified by age and gender was used to allocate rural New Zealand school students to the wait-list control or PRT group.Intervention:Participants were prescribed two sets (eight repetitions per set) of 11 exercises targeting all the major muscle groups at high intensity.Primary Outcome:Waist circumference; secondary outcomes included whole body fat, muscular fitness (one repetition maximum), cardiorespiratory fitness (peak oxygen consumption during a treadmill test), lipids, insulin sensitivity and fasting glucose.Results:Of the 78 children (32 girls and 46 boys; mean age 12.2(1.3) years), 51% were either overweight (33%) or obese (18%). High-intensity PRT significantly improved waist circumference (mean change PRT −0.8 (2.2) cm vs +0.5 (1.7) cm control; F=7.59, P=0.008), fat mass (mean change PRT +0.2 (1.4) kg vs +1.0 (1.2) kg control; F=6.00, P=0.017), percent body fat (mean change PRT –0.3 (1.8)% vs +1.2 (2.1)% control; F=9.04, P=0.004), body mass index (mean change PRT −0.01 (0.8) kg m−2 vs +0.4 (0.7) kg m−2 control; F=6.02, P=0.017), upper body strength (mean change PRT+11.6(6.1) kg vs +2.9(3.7) kg control; F=48.6, P<0.001) and lower body strength (mean change PRT +42.9(26.6) kg vs +28.5(26.6) kg control; F=4.72, P=0.034) compared to the control group. Waist circumference decreased the most in those with the greatest baseline relative strength (r=−0.257, P=0.036), and greatest relative (r=−0.400, P=0.001) and absolute (r=0.340, P=0.006) strength gains during the intervention.Conclusion:Isolated high-intensity PRT significantly improves central and whole body adiposity in association with muscle strength in normal-weight and overweight children. The clinical relevance and sustainability of these changes in adiposity should be addressed in future long-term studies.International Journal of Obesity (2008) 32, 1016–1027; doi:10.1038/ijo.2008.5; published online 19 February 2008 [ABSTRACT FROM AUTHOR]

Obesity and metabolic syndrome are increasingly recognized as major risk factors for cardiovascular disease. Herein we show that Krüppel-like transcription factor 5 (KLF5) is a crucial regulator of energy metabolism. Klf5+/− mice were resistant to high fat–induced obesity, hypercholesterolemia and glucose intolerance, despite consuming more food than wild-type mice. This may in part reflect their enhanced energy expenditure. Expression of the genes involved in lipid oxidation and energy uncoupling, including those encoding carnitine-palmitoyl transferase-1b (Cpt1b) and uncoupling proteins 2 and 3 (Ucp2 and Ucp3), was upregulated in the soleus muscles of Klf5+/− mice. Under basal conditions, KLF5 modified with small ubiquitin-related modifier (SUMO) proteins was associated with transcriptionally repressive regulatory complexes containing unliganded peroxisome proliferator–activated receptor-δ (PPAR-δ) and co-repressors and thus inhibited Cpt1b, Ucp2 and Ucp3 expression. Upon agonist stimulation of PPAR-δ, KLF5 was deSUMOylated, and became associated with transcriptional activation complexes containing both the liganded PPAR-δ and CREB binding protein (CBP). This activation complex increased the expression of Cpt1b, Ucp2 and Ucp3. Thus, SUMOylation seems to be a molecular switch affecting function of KLF5 and the transcriptional regulatory programs governing lipid metabolism. [ABSTRACT FROM AUTHOR]

Gastric emptying regulates food intake. Oleoylethanolamide (OEA), an endogenous acylethanolamide chemically related to the endocannabinoid anandamide, inhibits food intake, but its effect on gastric emptying is unknown. Here, we investigated the effect and the role of OEA on gastric emptying in mice fed either a standard (STD) or a high-fat diet (HFD) for 14 weeks. Gastric emptying was reduced by OEA, but not by its saturated analog, palmitoylethanolamide. The effect of OEA was unaffected by rimonabant (cannabinoid CB1 receptor antagonist), SR144528 (cannabinoid CB2 receptor antagonist), 5′-iodoresiniferatoxin (transient receptor potential vanilloid type 1 antagonist), or MK886 (peroxisome proliferator-activated receptor-α) antagonist. Compared to STD mice, HFD mice showed delayed gastric emptying and higher levels of gastric OEA. HFD-induced increase in OEA levels was accompanied by increased expression of the OEA-synthesizing enzyme N-acyl-phosphatidylethanolamine-selective phospholipase D and decreased expression of the OEA-degrading enzyme fatty acid amide hydrolase. These results might suggest that elevation of gastric OEA could possibly contribute to the delayed gastric emptying observed in HFD-fed animals. HFD regulates OEA levels in the stomach through an increase of its biosynthesis and a decrease of its enzymatic degradation. The inhibitory effect of OEA on gastric emptying here observed might underlie part of the anorexic effects of this compound previously reported. [ABSTRACT FROM AUTHOR]

Objective:Obese patients with schizophrenia being treated with clozapine and non-psychiatric obese are often assumed to share the same physiological changes in obesity. The aim of this study was to identify possible metabolic and hormonal differences between non-psychiatric obese subjects (OB) and obese patients with schizophrenia being treated with clozapine (OSC).Subjects:Fifty-one normal healthy subjects (Nor, body mass index (BMI):23.2±0.3), 50 OB (BMI:31.7±0.7) and 71 OSC (BMI:30.4±0.5).Measurements:Anthropometric, metabolic and hormonal parameters were determined by anthropometry, enzyme autoanalyzer, immunoassay and enzyme-linked immunosorbent assay.Results:Triglyceride, total cholesterol divided by high-density lipoprotein (HDL) cholesterol (TC/HDL) and leptin levels were significantly higher whereas the HDL and the molar ratio of insulin-like growth factor-1 (IGF-1), and insulin-like growth factor binding protein (IGFBP)-3 levels were significantly lower in both OB and OSC groups than those in the Nor group. Compared to normal subjects, insulin and homeostasis model assessment (HOMA) index levels were significantly higher in OSC, and, in OSC, insulin sensitivity and insulin-like growth factor (IGF)-1 were significantly lower. Although the anthropometric parameters in the OB and OSC groups were similar, in the OSC group the waist-to-hip ratio (WHR), insulin levels and HOMA index were significantly higher, while insulin sensitivity, cholesterol, low-density lipoprotein (LDL) cholesterol, TC/HDL, LDL/HDL, IGF-1 and IGF-1/IGFBP-3 molar ratio were lower, than those of the OB group.Conclusion:Insulin homeostasis and lipid profiles in clozapine-treated schizophrenic obesity were different from those in non-psychiatric obesity with similar anthropometric parameters, body weight and BMI. Among the three groups, the highest fasting insulin, the lowest insulin sensitivity and the highest HOMA index occurred in the OSC group. The OSC group was characterized by impaired glucose–insulin homeostasis, abnormal lipid profiles and hormonal changes in the GH-IGF-IGFBP axis and in leptin.International Journal of Obesity (2008) 32, 436–442; doi:10.1038/sj.ijo.0803750; published online 23 October 2007 [ABSTRACT FROM AUTHOR]

Objective:To investigate the prevalence of metabolic syndrome and its associated risk factors in a cohort of university freshmen.Design:A cross-sectional study in a university health center in North Taiwan.Subjects:A total of 8226 students (mean age: 19.2±2.3 years) receiving pre-entrance health examinations and lifestyle questionnaires during the 2005–2006 academic year were recruited.Measurements:A fasting plasma glucose, lipids, uric acid and hepatitis B serology were measured for each subject. The prevalence of metabolic syndrome and its individual components were examined using the America Heart Association and National Heart Lung Blood Institute criteria. The risk factors for metabolic syndrome were identified using a multivariate logistic regression analysis.Results:The prevalence of overweight, obesity and metabolic syndrome was 12.7% (17.0% in men and 7.6% in women), 13.0% (18.4% in men and 6.4% in women) and 4.6% (6.4% in men and 2.4% in women). The risk for metabolic syndrome increased with an increase of body mass index and plasma uric acid level, and decreased with the vigorous physical activity and current alcohol drinking. Furthermore, as compared to subjects with seroprotective titers from hepatitis B vaccination (anti-HBs(+) and anti-HBc(−)), those without protective titers of anti-HBs after vaccination or without hepatitis B infection (anti-HBs(−) and anti-HBc(−)) had 34% higher risk for metabolic syndrome, and those with natural infection of hepatitis B (anti-HBc(+)) had 58% higher risk for metabolic syndrome.Conclusions:Overweight, obesity and metabolic syndrome were more common among men than women in university freshmen. Hepatitis B vaccination with anti-HBs(+) was associated with a lower risk of metabolic syndrome as compared to anti-HBs(−). However, hepatitis B infection presented with anti-HBc(+) was associated with a higher risk of metabolic syndrome. The interplay between hepatitis B infection, hepatitis B vaccination and metabolic syndrome needs further investigation.International Journal of Obesity (2008) 32, 474–480; doi:10.1038/sj.ijo.0803753; published online 23 October 2007 [ABSTRACT FROM AUTHOR]

Background:Adult obesity prevalence is influenced by rates of weight gain or loss among individual persons, but few studies have measured individual weight change in large populations. Changes in weight may not coincide with changes in the lipid accumulation product (LAP), a continuous index derived from waist circumference and triglycerides concentration for estimating excess lipids.Design and measurements:Descriptive report of longitudinal changes from US studies that included body mass index (BMI, kg/m2) and LAP.Subjects:A total of 16 763 white and black adults studied between 1989 and 1996 in three observational cohorts (Coronary Artery Risk Development in Young Adults, Atherosclerosis Risk in Communities Study and Cardiovascular Health Study).Results:The means of individual annual changes in BMI were positive for young adults, but the mean changes were reduced at older ages (P for linear trend <0.001), becoming negative after 73–83 years old. These mean, individual changes in BMI, specific to sex and age, were approximately 0.1 U/year greater than those reported from previous, representative, longitudinal measurements collected in the United States between 1971 and 1984. Mean, individual annual changes in LAP were strongly positive before middle age. For men, the annual LAP changes were reduced at older ages (P linear trend <0.05). For women, they were greater at older ages (white women, P<0.001) or remained unchanged (black women, P>0.3). With increasing age, there was a greater proportion of persons whose positive LAP change was accompanied by simultaneous BMI change that was negative or zero.Conclusions:These longitudinal observations made during 1989–1996 suggest greater annual changes in BMI compared to an adult cohort studied during 1971–1984. As estimated by LAP, adults of all ages tended to accumulate excess lipids, including circumstances in which they lost weight.International Journal of Obesity (2008) 32, 136–143; doi:10.1038/sj.ijo.0803697; published online 7 August 2007 [ABSTRACT FROM AUTHOR]

Lumbar radicular pain is a fairly common health problem, yet its risk factors are far from clear. There are no published systematic reviews on associations between cardiovascular or lifestyle risk factors and lumbar radicular pain or sciatica. The aim of this systematic literature review was to assess associations between these risk factors and lumbar radicular pain or sciatica. We conducted a systematic search of the Medline database for all original articles on lumbar radicular pain or sciatica published until August 2006. Twenty-two papers from 19 studies were included in the review. Overweight or obesity was associated with sciatica in most of the case-control and cohort studies. Some studies showed an increased risk of lumbar radicular pain in smokers with a long smoking history or in those with high levels of physical activity. A few case-control studies showed an association between serum C-reactive protein and sciatica. No consistent associations were found for serum lipids levels or high blood pressure. In summary, the associations of overweight, long smoking history, high physical activity and a high serum C-reactive protein level with lumbar radicular pain or sciatica were substantiated by the present review. However, more prospective studies are needed in order to further clarify these associations and the mechanisms of action. [ABSTRACT FROM AUTHOR]

Objective:To determine whether increased expression of macrophage markers and of inflammatory markers in subcutaneous adipose tissue is associated with liver fat in human obesity. We also determined whether expression of TNF (gene encoding TNF-α), HSD11B1 (gene encoding 11β-HSD-1) and RETN (gene encoding resistin) in cultured monocyte-derived macrophages differs between obese/overweight and non-obese subjects.Design:Cross-sectional comparison of obese/overweight and non-obese subjects with respect to adipose tissue gene expression, gene expression in monocyte-derived macrophages, liver fat content and in vivo insulin sensitivity.Subjects:Adipose tissue gene expression, gene expression in monocyte-derived macrophages, liver fat content and in vivo insulin sensitivity: 10 healthy non-obese (24.2±1.0 kg/m2) and 10 healthy obese/overweight (33.1±1.7 kg/m2) women. Gene expression in monocyte-derived macrophages: seven healthy non-obese (22.1±0.7 kg/m2) and seven healthy obese/overweight (36.9±2.2 kg/m2) women.Measurements:Adipose tissue biopsies and blood samples for isolation of peripheral mononuclear cells were taken after an overnight fast. Liver fat content was measured using magnetic resonance proton spectroscopy. Whole body insulin sensitivity was measured using the hyperinsulinemic euglycemic clamp technique. Expression levels of TNF, HSD11B1, RETN and the macrophage markers CD68 and ITGAM were determined by real-time PCR.Results:In adipose tissue, expression of HSD11B1, ITGAM and CD68 was significantly increased in the obese/overweight as compared to the non-obese group. Expression of all these genes was closely positively correlated with liver fat content and inversely correlated with whole body insulin sensitivity. The associations between expression of CD68, ITGAM and HSD11B1 and liver fat were independent of obesity. There were no differences in TNF, HSD11B1, RETN or CD68 gene expression basally or after stimulation with lipopolysaccharide in monocyte-derived macrophages between obese/overweight and non-obese subjects.Conclusion:Accumulation of fat in the liver is associated with increased adipose tissue inflammation independent of obesity.International Journal of Obesity (2007) 31, 1617–1625. doi:10.1038/sj.ijo.0803635; published online 24 April 2007 [ABSTRACT FROM AUTHOR]

Objective:To assess the effect of weight loss on the plasma lipid and remnant-like lipoprotein cholesterol (RLPc) response to a high-fat or a high-carbohydrate meal in a population of obese women.Design:Nutritional intervention study.Subjects:Sixteen obese women (mean body mass index (BMI): 37.6±5 kg/m2).Methods:Subjects were asked to follow an energy-restricted diet (800 kcal/day) for 7 weeks, followed by a 1-week maintenance diet. Before and after weight loss, each participant was given (in random order) two iso-energetic meals containing either 80% fat and 20% protein (the high-fat meal) or 80% carbohydrate and 20% protein (the high-carbohydrate meal). Blood samples were collected over the following 10-h period. A two-way analysis of variance with repeated measures was used to assess the effect of the meal and postprandial time on biological variables and postprandial responses (notably RLPc levels).Results:Weight loss was associated with a significant decrease in fasting triglyceride (P=0.0102), cholesterol (P<0.0001), low-density lipoprotein cholesterol (P=0.0003), high-density lipoprotein-cholesterol (P=0.0009) and RLPc (P=0.0015) levels. The triglyceride response to the high-fat meal was less intense after weight reduction than before (interaction P<0.002). This effect persisted after adjustment on baseline triglyceride levels. The triglyceride response to the high-carbohydrate meal was biphasic (i.e. with two peaks, 1 and 6 h after carbohydrate intake). After adjustment on baseline values, weight reduction was associated with a trend towards a reduction in the magnitude of the second triglyceride peak (interaction P<0.054). In contrast, there was no difference in postprandial RLPc responses before and after weight loss, again after adjustment on baseline levels.Conclusion:Our data suggest that weight loss preferentially affects postprandial triglyceride metabolism.Sponsorship:Insudiet company (France), Conseil Regional Nord Pas de Calais and Institut Pasteur de Lille.European Journal of Clinical Nutrition (2007) 61, 711–718; doi:10.1038/sj.ejcn.1602603; published online 17 January 2007 [ABSTRACT FROM AUTHOR]

Objectives:To compare obesity measures, metabolic profiles and dietary fatty acids in lean and obese dyslipideamic Asian Indian male subjects.Design:Cross-sectional.Settings:Asian Indians living in the eastern part of India.Subjects:One hundred and thirty (Group I: lean control, n=50; Group II: lean dyslipidaemic, n=40 and Group III: obese dyslipidaemic, n=40) Asian Indian male subjects (30 years) living in the eastern part of India.Methods:Anthropometric measures namely height, weight, circumferences of waist (WC) and hip, lipids (total cholesterol (TC) and triglycerides (TG)), lipoproteins (high- (HDL) and low-density lipoproteins (LDL)), fasting plasma glucose (FPG) and dietary fatty acids were obtained from each participant. Obesity measures, that is, body mass index (BMI), waist–hip ratio (WHR) and conicity index (CI) were subsequently calculated from anthropometric measures. Obesity was defined as individuals having BMI25 kg/m2. Subjects with one or more of the following conditions were considered as dyslipidaemic: TG2.3 mmol/l, TC6.2 mmol/l, or TC/HDL4.4 mmol/l. Daily intake of nutrients as well as saturated (SFA), monounsaturated (MUFA) and polyunsaturated fatty acids (PUFA) were estimated by adding together all the foodstuffs consumed on weekly and monthly manner. Conversion of foodstuffs into nutrients was performed according to standard nutritive values of Indian foodstuffs.Results:Analysis of variance with Scheffe's post hoc test revealed that Group I had significantly lower mean compared to both Group II and Group III for age, WC, WHR, CI, TC, TG, LDL, FPG, total carbohydrates intake and intake of trans fatty acids. On the other hand, Group I had significantly lower mean than Group III only for BMI as well as intake of total proteins, total fats, total energy and erucic acids. Although, Group I had significantly greater mean compared to both Group II and Group III for HDL, UFA/SFA, MUFA/SFA and PUFA/SFA. Pearson's partial correlations (controlling for age and total energy) revealed that central obesity measures (WC, WHR and CI) had significant association with dietary fatty acids and their ratios. Furthermore, partial correlations (controlling for age) also showed that the ratios of unsaturated to SFA had significant negative association with lipids, lipoproteins (except HDL) and plasma glucose. Discriminant function analysis revealed that overall 78% of all entries were positively (correctly) classified in three groups using fatty acids and their ratios.Conclusion:It seems rational to argue that while dealing with dyslipidaemic Asian Indians, clinicians should consider obesity measures, metabolic profiles and dietary fatty acids simultaneously to better comprehend the condition (s).European Journal of Clinical Nutrition (2007) 61, 412–419. doi:10.1038/sj.ejcn.1602534; published online 27 September 2006 [ABSTRACT FROM AUTHOR]

Objective:To determine the role of macronutrients oxidation ability in the postprandial response to a high lipid load in the mechanisms conferring resistance or susceptibility to obesity.Subjects and design:Nine lean and nine obese young male subjects with habitual similar high-fat intake (>40 % of energy) and comparable physical activity were selected and categorized as ‘resistant’, those who remained lean (body mass index (BMI) <25 kg/m2), and ‘susceptible’, those who were obese (BMI>30 kg/m2). Fasting blood samples were taken for the evaluation of blood metabolic and hormonal variables. Resting metabolic rate (RMR) and substrates oxidation were measured by indirect calorimetry, in the fasting state and every 30 min for 3 h after a rich lipid meal (fat 94.7%) supplied to cover the 50% of the volunteers energy requirements. The study was performed at the Metabolic Unit of the University of Navarra.Results:Fasting RMR and lipid oxidation were higher in obese–susceptible subjects. However, similar values were found in both groups after adjustment for fat mass and free fat mass. The cumulative postprandial fat oxidation was also similar in both groups (despite having different tissue metabolic activity), whereas cumulative carbohydrate oxidation was lower in the obese–susceptible group. The thermic effect of food (% of dietary induced thermogenesis) was lower (P<0.05) in the susceptible–obese subjects. The energy and fat balance were more positive in the obesity-susceptible individuals after the high fat load, who also showed higher fasting homeostatic model assessment index, low-density lipoprotein-cholesterol and triacylglyceride levels, hyperleptinemia and hypoadiponectinemia.Conclusion:Lean–resistant individuals came closer to achieving fat balance than obese–susceptible subjects. These metabolic and hormonal differences are probably genetically determined.European Journal of Clinical Nutrition (2007) 61, 166–174. doi:10.1038/sj.ejcn.1602500; published online 9 August 2006 [ABSTRACT FROM AUTHOR]

Objective:To compare the value of body fat mass (%FM) to indirect measures of general (body mass index (BMI)) and central adiposity (waist circumference (WC); waist-to-height ratio (WC/ht)) for the prediction of overweight- and obesity-related metabolic risk in a study population with a high prevalence of metabolic syndrome (MSX).Methods:BMI, WC, WC/ht, body composition (by air-displacement plethysmography) and metabolic risk factors: triglycerides, cholesterol, HDL-cholesterol (HDL-C), uric acid, systolic blood pressure (BPsys), insulin resistance by homeostasis model assessment (HOMA-IR) and C-reactive protein (CRP) were measured in 335 adults (191 women, 144 men; mean age 53 ±13.9 years, prevalence of MSX 30%).Results:When compared with BMI and WC, %FM showed weaker associations with metabolic risk factors, except for CRP and BPsys in men. In women, HDL-C and HOMA-IR showed the closest correlations with BMI. For all other risk factors, WC or WC/ht were the best predictors in both sexes. Differences in the strength of correlations between an obesity index and different risk factors exceeded the differences observed between all obesity indices within one risk factor. In stepwise multiple regression analyses, WC/ht was the main predictor of metabolic risk in both sexes combined. However, analysis of the area under receiver operating characteristic curves for prediction of the prevalence of 2 component traits of the MSX revealed a similar accuracy of all obesity indices.Conclusions:At the population level, measurement of body FM has no advantage over BMI and WC in the prediction of obesity-related metabolic risk. Although measures of central adiposity (WC, WC/ht) tended to show closer associations with risk factors than measures of general adiposity, the differences were small and depended on the type of risk factor and sex, suggesting an equivalent value of methods.International Journal of Obesity (2006) 30, 475–483. doi:10.1038/sj.ijo.0803144; published online 1 November 2005 [ABSTRACT FROM AUTHOR]

Objective:Oxidative stress may be the unifying mechanism underlying the development of comorbidities in obesity. Evidence suggests that a clustering of sources of oxidative stress exists in obesity: hyperglycemia, hyperleptinemia, increased tissue lipid levels, inadequate antioxidant defenses, increased rates of free radical formation, enzymatic sources within the endothelium, and chronic inflammation.Method:This review provides a summary of the available evidence on systemic oxidative stress in humans and specific metabolic pathways by which obesity may elevate systemic oxidant stress. The authors suggest possible methods of reducing oxidative stress such as antioxidant supplementation, caloric restriction and/or physical activity and surgical intervention to combat free radicals and reduce adipose tissue.Results:Obesity is associated with oxidative stress and can be reduced with weight loss (regardless of exercise or surgery induced weight loss), caloric restriction or antioxidant rich diets.Conclusion:Oxidative stress levels are elevated in human obesity, and these levels are modifiable with various lifestyle modifications and surgical interventions.International Journal of Obesity (2006) 30, 400–418. doi:10.1038/sj.ijo.0803177; published online 22 November 2005 [ABSTRACT FROM AUTHOR]

Introduction:Although lipid profiles tend to worsen with age, it is not fully known if such age-related changes are influenced primarily by body composition and lifestyle or by other aspects of aging.Objective:We investigated the extent to which the fat and fat-free components of body mass index (BMI) and lifestyle factors influence patterns of change in lipids independent of age.Design:Serial data were analyzed using sex-specific longitudinal models. These models use serial data from individuals to assume a general pattern of change over time, while allowing baseline age and the rate of change to vary among individuals.Subjects:Serial data were obtained from 940 examinations of 269 healthy white participants (126 men, 143 women), aged 40–60 years, in the Fels Longitudinal Study.Measurements:Measurements included age, the fat (FMI) and fat-free mass (FFMI) components of BMI, high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C), triglycerides (TG), total cholesterol (TC), fasting glucose and insulin, physical activity, alcohol use and smoking, and women's menopausal status and estrogen use.Results:In both sexes, increased FMI was significantly associated with increased LDL-C, TG and TC, and decreased HDL-C. Increased FFMI was significantly related to decreased HDL-C and increased TG. Independent age effects remained significant only for LDL-C and TC in men and TC in women. Increased insulin was significantly related to increased TG in women. Moderate alcohol consumption was associated with higher HDL-C in men. Physical activity lowered male LDL-C and TC levels, and increased female HDL-C levels. Menopause was associated with increases in LDL-C. Premenopausal women not using estrogen had significantly lower HDL-C, TG, and TC than postmenopausal women taking estrogen.Conclusions:(1) Age is an important independent predictor for LDL-C and TC in men, and TC in women, but it is not as influential as body composition and lifestyle on HDL-C and TG in men and women, and LDL-C in women. (2) Increasing FMI is the major contributor to elevated TC, LDL-C and TG levels, and decreased HDL-C levels in men and women. (3) FFMI significantly influences HDL and TG levels in both sexes. (4) Maintaining a lower BMI via a reduced fat component may be more beneficial in lowering CVD risks than other factors.International Journal of Obesity (2006) 30, 251–260. doi:10.1038/sj.ijo.0803129; published online 25 October 2005 [ABSTRACT FROM AUTHOR]

Objective: To investigate whether low-carbohydrate diets are efficient for reduction of body weight and through which mechanism.Design: A couple of studies using low-carbohydrate diets in the treatment of obesity are reviewed. Mechanisms for explaining the reduced appetite are described in relation to knowledge on regulation of appetite for fat and carbohydrate.Results: Studies with low-carbohydrate diets demonstrate a rapid weight loss, being more pronounced after 3 and 6 months compared to low-fat diets. After 12 months there is no difference between the low-carbohydrate and the conventional low-fat diet on weight loss. Both diets lead to improvements in risk factors for coronary heart disease, the low-carbohydrate diet leading to a greater decrease in serum triglycerides and increase in HDL cholesterol compared to the low-fat diet. Blood pressure, insulin sensitivity and LDL cholesterol were improved to a similar degree by the two diets. The mechanism for the rapid weight loss with the low-carbohydrate diet is a suppressed appetite, first through the high-protein content of the diet, second through the ketogenic nature of the diet with satiety signals for fat being active and third through the absence of hunger-promoting carbohydrate components like sucrose and/or fructose.Conclusion: A rapid initial weight loss occurs with a low-carbohydrate diet due to a suppressed appetite. There is as yet no indication of an increased metabolic rate and an increased thermogenesis by the low-carbohydrate diet. The safety and efficacy of low-carbohydrate diets have to await further studies. [ABSTRACT FROM AUTHOR]

Objective: Use the meta-analytic approach to examine the effects of aerobic exercise on lipids and lipoproteins in overweight and obese adults.Data Sources: (1) Computerized literature searches, (2) cross-referencing from review and original articles, (3) hand searching, and (4) expert review of reference list.Study Selection: (1) randomized controlled trials, (2) aerobic exercise > or =8 weeks, (3) adult humans > or =18 y of age, (4) all subjects overweight or obese (BMI > or =25 kg/m(2)), (5) studies published in journal, dissertation, or master's thesis format, (6) studies published in the English-language, (7) studies published between 1 January 1955 and 1 January 2003, (8) assessment of one or more of the following lipid and/or lipoprotein variables: total cholesterol (TC), high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), and triglycerides (TG).Data Abstraction: Dual-coding by the first two authors (inter-rater agreement=0.96).Results: In total, 13 studies representing 31 groups (17 exercise, 14 control), 613 subjects (348 exercise, 265 control), and up to 17 outcomes were available for pooling. Across all categories, random-effects modeling resulted in statistically significant improvements for TC (X +/- s.e.m., - 3.4+/-1.7 mg/dl, 95% CI, - 6.7 to - 0.2 mg/dl) and TG (X +/-s.e.m., - 16.1+/-7.3 mg/dl, 95% CI, - 30.2 to - 2.1 mg/dl) but not HDL (X +/- s.e.m., 1.6+/-0.8 mg/dl, 95% CI, - 0.02 to 3.2 mg/dl) or LDL (X +/-s.e.m., - 0.5+/-1.3 mg/dl, 95% CI, - 3.0 to 2.0 mg/dl). Changes were equivalent to improvements of 2% (TC), 11% (TG), 3% (HDL), and 0.3% (LDL). After conducting sensitivity analyses (each study deleted from the model once), only decreases in TG remained statistically significant. Increases in HDL were associated with increases in maximum oxygen consumption (VO(2 max) in ml/kg/min, r=0.75, P=0.002) and decreases in body weight (r=0.77, P<0.001), while decreases in LDL were associated with decreases in body weight (r=0.75, P=0.009).Conclusions: Aerobic exercise decreases TG in overweight and obese adults. However, a need exists for additional randomized controlled trials in various overweight and/or obese populations above and beyond those included in our analysis. [ABSTRACT FROM AUTHOR]

Life is a combustion, but how the major fuel substrates that sustain human life compete and interact with each other for combustion has been at the epicenter of research into the pathogenesis of insulin resistance ever since Randle proposed a‘glucose-fatty acid cycle’in 1963. Since then, several features of a mutual interaction that is characterized by both reciprocality and dependency between glucose and lipid metabolism have been unravelled, namely:the inhibitory effects of elevated concentrations of fatty acids on glucose oxidation (via inactivation of mitochondrial pyruvate dehydrogenase or via desensitization of insulin-mediated glucose transport),the inhibitory effects of elevated concentrations of glucose on fatty acid oxidation (via malonyl-CoA regulation of fatty acid entry into the mitochondria), and more recentlythe stimulatory effects of elevated concentrations of glucose on de novo lipogenesis, that is, synthesis of lipids from glucose (via SREBP1c regulation of glycolytic and lipogenic enzymes).This paper first revisits the physiological significance of these mutual interactions between glucose and lipids in skeletal muscle pertaining to both blood glucose and intramyocellular lipid homeostasis. It then concentrates upon emerging evidence, from calorimetric studies investigating the direct effect of leptin on thermogenesis in intact skeletal muscle, of yet another feature of the mutual interaction between glucose and lipid oxidation: that of substrate cycling between de novo lipogenesis and lipid oxidation. It is proposed that this energy-dissipating substrate cycling that links glucose and lipid metabolism to thermogenesis could function as a‘fine-tuning’mechanism that regulates intramyocellular lipid homeostasis, and hence contributes to the protection of skeletal muscle against lipotoxicity.International Journal of Obesity (2004) 28, S29-S37. doi:10.1038/sj.ijo.0802861 [ABSTRACT FROM AUTHOR]

The measurement of fat balance (fat input minus fat output) involves the accurate estimation of both metabolizable fat intake and total fat oxidation. This is possible mostly under laboratory conditions and not yet in free-living conditions. In the latter situation, net fat retention/mobilization can be estimated based on precise and accurate sequential body composition measurements. In case of positive balance, lipids stored in adipose tissue can originate from dietary (exogenous) lipids or from nonlipid precursors, mainly from carbohydrates (CHOs) but also from ethanol, through a process known as de novo lipogenesis (DNL). Basic equations are provided in this review to facilitate the interpretation of the different subcomponents of fat balance (endogenous vs exogenous) under different nutritional circumstances. One difficulty is methodological: total DNL is difficult to measure quantitatively in man; for example, indirect calorimetry only tracks net DNL, not total DNL. Although the numerous factors (mostly exogenous) influencing DNL have been studied, in particular the effect of CHO overfeeding, there is little information on the rate of DNL in habitual conditions of life, that is, large day-to-day fluctuations of CHO intakes, different types of CHO ingested with different glycemic indexes, alcohol combined with excess CHO intakes, etc. Three issues, which are still controversial today, will be addressed: (1) Is the increase of fat mass induced by CHO overfeeding explained by DNL only, or by decreased endogenous fat oxidation, or both? (2) Is DNL different in overweight and obese individuals as compared to their lean counterparts? (3) Does DNL occur both in the liver and in adipose tissue? Recent studies have demonstrated that acute CHO overfeeding influences adipose tissue lipogenic gene expression and that CHO may stimulate DNL in skeletal muscles, at least in vitro. The role of DNL and its importance in health and disease remain to be further clarified, in particular the putative effect of DNL on the control of energy intake and energy expenditure, as well as the occurrence of DNL in other tissues (such as in myocytes) in addition to hepatocytes and adipocytes.International Journal of Obesity (2004) 28, S3-S11. doi:10.1038/sj.ijo.0802852 [ABSTRACT FROM AUTHOR]

Obesity is associated with increased storage of lipids in nonadipose tissues like skeletal muscle, liver, and pancreaticßcells. These lipids constitute a continuous source of long-chain fatty acyl CoA (LC-CoA) and derived metabolites like diacylglycerol and ceramide, acting as signalling molecules on protein kinases activities (in particular, the family of PKCs), ion channel, gene expression, and protein acylation. In skeletal muscle, the increase in LC-CoA and diacylglycerol translocates and activates specific protein kinase C (PKC) isoforms, which will phosphorylate IRS-1 on serine, preventing its phosphorylation on tyrosine and association with PI3 kinase. This interrupts the insulin signalling pathway leading to the stimulation of glucose transport. In pancreaticßcells, short-term excess of fatty acids or LC-CoA activates PKC and also directly stimulates insulin exocytosis. Long-term exposure to free fatty acids (FFA) leads to an increased basal and blunted glucose-stimulated insulin secretion by affecting gene expression, increase in KATP channel activity, and uncoupling of the mitochondria. In addition, the saturated FFA palmitate increases cell death by apoptosis via increase in ceramide synthesis.International Journal of Obesity (2004) 28, S53-S57. doi:10.1038/sj.ijo.0802857 [ABSTRACT FROM AUTHOR]

The potential lipotoxic effect of intramyocellular triglyceride (IMTG) accumulation has been suggested to be a major component in the development of insulin resistance. Increased levels of IMTGs correlate with insulin resistance in both obese and diabetic patients, but this relationship does not exist in endurance trained (ETr) subjects. This may be, in part, related to differences in the gene expression and activities of key enzymes involved in fatty acid transport and oxidation as well as in the perodixation status of the IMTGs in obese/diabetic patients as compared with ETr subjects. Disruptions in fat and lipid homeostasis in skeletal muscle have been shown to activate protein kinase C (PKC), which acts on several downstream signalling pathways, including the insulin and the I?B kinase (IKK)/NF?B signalling pathways. Additionally, an increased peroxidation of IMTGs may reduce insulin sensitivity by increasing TNFa, which is known to increase the expression of suppressor of cytokine signalling proteins (SOCS). A common characteristic observed when activating both PKC and TNFa/SOCS3 is the inhibition of tyrosine phosphorylation of IRS-1 and subsequently an inhibition of its activation of downstream signalling molecules. These may be important players in the development of insulin resistance and understanding their activation and expression in both obese and ETr humans should assist in understanding how and why IMTGs become lipotoxic.International Journal of Obesity (2004) 28, S66-S71. doi:10.1038/sj.ijo.0802859 [ABSTRACT FROM AUTHOR]

OBJECTIVE:: This study sought to determine the relationship between levels of the inflammatory marker, C-reactive protein (CRP), cardiovascular risk factors and oral contraceptive use in young adults. DESIGN:: Cross-sectional study of a community cohort. SUBJECTS:: A total of 822 men and women aged 26?y. MEASUREMENTS:: CRP, body mass index (BMI), blood pressure, lipid and lipoprotein levels, smoking status, socioeconomic status, health status, and hormonal contraceptive use in women. RESULTS:: Multiple regression analysis showed that obesity was independently related to CRP with an increase in ratio CRP of 1.03 (95% CI 1.01, 1.05) for men and 1.07 (1.05, 1.09) for women associated with a 1?kg/m2 increase in BMI. In women, combined oral contraceptive use was associated with a ratio change in CRP of 1.52 (1.27, 1.82) compared with nonusers. Other independent determinants of CRP in men and women were apolipoprotein B level, systolic blood pressure and apolipoprotein A1 in men. Univariate analysis showed that the relationship between CRP and BMI, systolic blood pressure and apolipoprotein B was significantly stronger in women than men. CONCLUSION:: These findings suggest that obesity is associated with inflammation independent of other cardiovascular risk factors that may contribute to an increased risk for cardiovascular disease in men and women. Elevated CRP related to combined oral contraceptive use may influence the rate of cardiovascular events in young women.International Journal of Obesity (2004) 28, 998-1003. doi:10.1038/sj.ijo.0802713 Published online 22 June 2004 [ABSTRACT FROM AUTHOR]

OBJECTIVES:: To estimate the prevalence of insulin resistance syndrome (IRS) in a representative sample of youth. To test for the independent contribution of insulin resistance (IR) and adiposity to clustering of metabolic risk factors. To identify the underlying components of IRS. To examine the relationship between adiposity and fasting plasma levels of free fatty acids (FFA). METHODS:: In 1999, we conducted a school-based survey of a representative sample of youth aged 9, 13 and 16?y in Quebec, Canada. Age-specific questionnaire data, standardized clinical measurements and a fasting blood sample were available for 2244 subjects. Fasting insulin and HOMA were used as surrogate measures of IR. RESULTS:: In all age-sex groups, adiposity indices, blood pressure (BP), plasma glucose and triglycerides (TG) increased significantly with increasing insulin quartiles while HDL cholesterol (HDL-C) decreased. The overall prevalence of IRS defined as hyperinsulinaemia combined with two or more risk factors including overweight, high systolic BP, impaired fasting glucose, high TG and low HDL-C, was 11.5% (95% CI: 10.2-12.9). There were no significant differences in the prevalence of IRS across ages or between sexes. The independent contribution of adiposity to clustering of risk factors was stronger than that of fasting insulin (or HOMA-IR). Factor analysis revealed three factors (BMI/insulin/lipids, BMI/insulin/glucose and diastolic/systolic BP) consistent across ages suggesting that more than one pathophysiologic process underlies IRS. Although elevation of FFA might be in the causal pathway linking obesity to IR, we did not detect any consistent association between measures of fatness and fasting plasma FFA. CONCLUSION:: IRS is highly prevalent in youth, even among children as young as age 9?y. Factor analysis identifies three physiologic domains within IRS with a unifying role for markers of IR and adiposity.International Journal of Obesity (2004) 28, 833-841. doi:10.1038/sj.ijo.0802694 Published online 1 June 2004 [ABSTRACT FROM AUTHOR]

OBJECTIVE:: To assess the relationship of fat mass (FM) and its distribution to hypertension and dyslipidemia in normal-weight Japanese individuals. DESIGN:: Cross-sectional study. SUBJECTS:: Apparently healthy Japanese subjects with a body mass index (BMI) between 20 and 23.5?kg/m2 (265 males and 741 females, age 21-69?y). MEASUREMENTS:: BMI, waist circumference (WC), waist-hip ratio (WHR), systolic and diastolic blood pressure, serum levels of total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-C) and triglyceride (TG) were measured. Low-density lipoprotein-cholesterol (LDL-C) was calculated by the Friedewald formula. Percentage fat mass (%FM) and trunk fat mass-leg fat mass ratio (FMtrunk/FMlegs) were obtained by dual-energy X-ray absorptiometry. RESULTS:: WC, WHR, %FM and FMtrunk/FMlegs were significantly correlated with TC, LDL-C, HDL-C and TG with the tendency of FMtrunk/FMlegs to show the strongest correlations. For %FM and FMtrunk/FMlegs in both sexes, odds ratios (ORs) of the third tertiles with respect to the first tertiles increased for LDL-C elevation, TG elevation and dyslipidemia. In males, ORs of the third tertiles of WC were significantly high for LDL-C elevation and dyslipidemia whereas those of WHR were high for TG elevation and dyslipidemia. ORs of the third tertiles of WC and WHR were significantly high for TG elevation in females. BMI was not associated with the risk of abnormal lipid levels. ORs for hypertension showed significant increases in none of the variables of obesity. CONCLUSIONS:: Excess accumulation of FM, especially to the upper body, was related to dyslipidemia in normal-weight subjects. Simple anthropometric variables, WC and WHR, may be useful for screening and management of dyslipidemia in these subjects.International Journal of Obesity (2004) 28, 242-247. doi:10.1038/sj.ijo.0802528 Published online 11 November 2003 [ABSTRACT FROM AUTHOR]

OBJECTIVE: To evaluate whether postprandial abnormalities of energy expenditure and/or lipid oxidation are present in healthy, normal-weight subjects with a strong family history of obesity and thus at high risk to become obese. DESIGN: Case-control study. SUBJECTS: A total of 16 young healthy men participated in the study. Eight subjects had both parents overweight (father's and mother's body mass index (BMI) > 25 kg/m[SUP2]) and eight had both parents with normal body weight (father's and mother's BMI < 25 kg/m[SUP2], respectively). The group of subjects with overweight parents was similar to that with normal-weight parents (control group) in terms of BMI (23.7 ± 1.7 vs 22.7 ± 1.1 kg/m[SUP2]) (M ± s.d.) and fat-free body mass (FFM) (60.5 ± 4.9 vs 58.4 ± 2.0 kg), but was slightly older than the control group (25.4 ± 3.3 vs 22.7 ± 2.4 y; P< 0.05). MEASUREMENTS: Energy expenditure (EE) was measured by indirect calorimetry, and blood samples were taken for the evaluation of metabolic variables in the fasting state and every hour for 8 h after a standard fat-rich meal (protein 15%, carbohydrate 34%, fat 51%, 4090 kJ). RESULTS: Fasting plasma glucose, cholesterol, HDL-cholesterol, triglyceride, free fatty acid (FFA) and leptin concentrations were similar in both groups of participants, but subjects with overweight parents has significantly lower plasma insulin concentrations (5.11 ± 0.51 vs 7.07 ± 1.56 μU/ml; P<0.007) and HOMA index of insulin resistance (1.1 ± 0.1 vs 1.6 ± 0.4; P<0.01). Postprandial plasma glucose, triglyceride, FFA and leptin concentrations were similar in the two groups, whereas insulin levels were significantly lower in the group with both parents overweight at 3, 5, 6, 7 and 8 h. Fasting and postprandial EE, and fasting lipid and carbohydrate oxidation were similar in both groups. On the contrary, postprandial carbohydrate oxidation (incremental area... [ABSTRACT FROM AUTHOR]

OBJECTIVE: The aim of this study was to examine changes in lipid profile and markers of insulin resistance with increasing body mass index (BMI) in the range 34-77 kg/m². In addition we compare the lipid profiles of severely obese patients with those of the Australian community. SUBJECTS AND METHODS: A total of 572 patients (85% F, 15% M) were assessed prior to gastric restrictive surgery. Conventional lipid profiles and markers of insulin resistance were measured. Lipids were compared with the Australian National Heart Foundation 1989 study (control group). RESULT: There was no difference in mean total cholesterol levels between the obese group (5.52 mmol/l) and the control group (5.47 mmol/1). The mean total cholesterol levels in the obese group fell with increasing BMI (r=-0.13, P<0.01). Obese subjects had elevated fasting triglyceride levels 1.96 mmol/l (control group, 1.12 mmol/l, P < 0.001), but levels did not change with increasing BMI (r=0.0, NS). HDL-C levels were lower, 1.21 mmol/l (control group 1.44 mmol/l, P < 0.001), and decreased with increasing BMI (r=-0.20, P<0.01). LDL-C levels were lower in obese men (3.65 mmol/l vs control group 4.17 mmol/l, P<0.01) but not women and levels fell with increasing BMI (r=-0.15, P<0.05). For the obese group, markers of insulin resistance (fasting plasma glucose, HbA1c, fasting plasma insulin and C-peptide) all rose significantly with increasing BMI. CONCLUSION: Raised total cholesterol is not a co-morbidity of severe obesity. There is a disparity between the conventional lipid measures and insulin resistance measures of the metabolic syndrome with increasing BMI. Conventional lipid measures may be poor indicators of dyslipidaemic risk in the severely obese. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To determine the metabolic alterations that lead to the neonatal administration of monosodium glutamate (MSG), which results in arrested growth and obesity. ANIMALS AND DESIGN: Wistar rats were injected 5 times, every other day, with 4 g of MSG/kg b.w. or with hyperosmotic saline (controls), within the first 10 days of life, and were studied at the age of 30 days. RESULTS: Body weight was lower, whereas adipocyte lipid content, cell diameter, surface area and volume were higher in MSG rats than in controls. Plasma glucose, insulin, NEFA, glycerol and triglyceride levels, and in vitro production of NEFA by lumbar fat pad pieces incubated under basal conditions or in the presence of epinephrine and epinephrine plus glucose in the media were lower in MSG than in control rats. In the same fat pad pieces, the conversion of 1- [sup 14]C-glycerol into fatty acids was always enhanced and its conversion into glyceride glycerol was enhanced when incubations were carried out in the presence of epinephrine or glucose. Both the hormone sensitive lipase activity and mRNA expression were lower in adipose tissue from MSG rats. Besides, the number of insulin receptors, lipid synthesis from U[sup 14]C glucose, ³H-2-deoxy D-glucose uptake and cellular GLUT4 translocation index were higher in adipocytes from MSG rats than from the controls. CONCLUSION: It is proposed that an enhanced insulin sensitivity in 1 month old MSG rats is responsible for the decreased lipolytic activity and enhanced glucose uptake. In addition, the enhanced lipogenesis and glycerol reutilization seen in their adipose tissue, disturbs the normal balance between fat depots breakdown and accumulation in favor of the latter. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To determine the mechanisms underlying the obesity-induced increase in myocardial lipid peroxidation in the fa/fa rat. We hypothesized that elevated heart work (ie rate-pressure product), an increased rate of superoxide (O[sub 2][sup ·-]) production, total myocardial lipid content, and/or insufficient antioxidant defenses are potential contributors to myocardial lipid peroxidation in obesity. DESIGN' Comparative, experimental study of myocardial tissue in 16-week-old lean control (Fa/?, normal diet), obese high-fat fed (Fa/?, 45% dietary fat), and obese fatty (fa/fa, normal diet) Zucker rats. MEASUREMENTS: Myocardial work (heart rate x systolic blood pressure), myocardial lipid content, oxidative and antioxidant enzyme activities (citrate synthase (CS), catalase (CAT), glutathione peroxidase (GPX), superoxide dismutase (SOD)), the rate of papillary muscle superoxide radical production in vitro, thiol content, basal and post-oxidative challenge myocardial lipid peroxidation levels using thiobarbituric reactive acid substances (TBARS) and lipid hydroperoxides (PEROX) as indices of lipid peroxidation. RESULTS: Compared to lean controls, the high-fat fed and fatty animals had similar elevations (P < 0.05) in myocardial TBARS and PEROX (23%, 25% and 29% 45%, respectively; P < 0.05), and elevated susceptibilities to oxidative stress in vitro following exposure to oxidizing agents (P < 0.05). Resting heart work was slightly higher (P < 0.05) in both the high-fat fed and fatty animals compared to controls. Myocardial lipid content, SOD activities and non-protein thiol (glutathione) levels were elevated (P < 0.05) in high-fat fed and fatty animals compared to controls. The rate of superoxide formation by isolated papillary muscles in vitro did not differ among groups (P < 0.05). Regression analysis revealed that the myocardial lipid content contributed most to myocardial lipid peroxidation (R²= 0.76, P< 0.05). CONCLUSIONS: Myocardial oxidative... [ABSTRACT FROM AUTHOR]