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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]

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]

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: 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]

OBJECTIVE: To determine the effect of exercise training (ET) on components of the insulin resistance syndrome (IRS) in obese children. DESIGN: Randomized, modified cross-over study, with subjects assigned to one of two conditions: (1) 4 months of ET followed by 4 months of no-ET; or (2) 4 months of no-ET followed by 4 months of ET. Measurements were made at three time points: 0, 4 and 8 months. SUBJECTS: 79 obese, but otherwise healthy children (age: 7-11 y, percent fat (%fat) 27-61%). MEASUREMENTS: Plasma lipid and lipoprotein concentrations, plasma insulin and glucose concentrations; %fat; submaximal heart rate (HR) as an index of fitness. EXERCISE TRAINING: ET was offered 5 d/week 40 min/d. For the 73 children who completed 4 months of ET, the mean attendance was 80% (that is, 4d/week) and the average HR during ET was 157 bpm. RESULTS: Significant (P<0.05) group x time interactions were found for plasma triglyceride (TG) and insulin concentrations and %fat. The average change for both groups, from just before ET to just after the 4 month ET was -0.24 mmol. I[sup -1] for TG, -25.4 pmol. I[sup -1] for insulin and -1.6 units for %fat. When Group I ceased ET, over the following 4 month period the average change for insulin was +26.6 pmol. I[sup -1] and for %fat +1.3 units. CONCLUSION: Some components (plasma TG, insulin, %fat) of the IRS are improved as a result of 4 months of ET in obese children. However, the benefits of ET are lost when obese children become less active. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To determine associations between overall adiposity, absolute and relative abdominal adiposity, and lipid concentrations in healthy older women. DESIGN: Cross-sectional analysis of baseline data. SUBJECTS: Subjects were 21 healthy, untrained older women (71±1 y) entering a randomized, controlled aerobic training program. MEASUREMENTS: Overall adiposity was assessed by anthropometry and the body mass index (BMI=kg/m2). Absolute and relative abdominal adiposity was determined by computed tomography (CT) and circumference measures. Fasting serum lipid concentrations of total-, high density lipoprotein (HDL)-, and low density lipoprotein (LDL)-cholesterol (C) and triglycerides (TGs) were determined by standard enzymatic procedures. RESULTS: Compared to the measures of overall adiposity, we observed much stronger correlations between measures more specific to absolute or relative abdominal adiposity and lipid concentrations. Visceral fat area was the strongest correlate of HDL-C (r=-0.75; P<0.001) and the total-/HDL-C ratio (r=0.86; P<0.001). The abdomen-to-hip circumference ratio (AHR) was strongly correlated with TGs (r=0.54; P<0.01), HDL-C (r=-0.69; P<0.001), and the total-/HDL-C ratio (r=0.75; P<0.001). CONCLUSION: Excess abdominal adiposity remains an important correlate of lipid metabolism, even in healthy older women of normal weight. Thus, overall obesity is not a necessary condition for the correlation between excess abdominal fat and metabolic risk among postmenopausal women. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To find out whether genetic alterations of the leptin receptor gene underlie human forms of obesity. DESIGN: Among 249 morbidly obese adults (body mass index, BMI≥40 kg/m2), we screened 30 patients with the highest serum leptin levels for alterations of their leptin receptor gene by single-strand conformation polymorphism (SSCP) technique. SUBJECTS: 249 severely obese subjects (present or past BMI≥40 kg/m2) and 138 lean controls (BMI≤25 kg/m2). MEASUREMENTS: DNA analysis was carried out using SSCP technique, sequencing and polymerase chain reaction (PCR) followed by digestion with the restriction enzyme RsaI. Serum leptin, glucose, insulin and lipid concentrations were determined in obese subjects. RESULTS: We were able to detect a pentanucleotide insertion (CTTTA) in the 3′-untranslated region of the leptin receptor gene. The presence of this pentanucleotide insert generates a putative stem-loop structure in the mRNA. Association studies were carried out on this variant. The frequency of the insertion allele did not differ between 249 obese (12.4%) and 138 lean (12.0%) subjects. There was no association of serum leptin, glucose or lipid levels with the pentanucleotide genotype in the obese individuals. However, when subjects without medication affecting insulin or glucose levels were considered, serum insulin levels were found to be lower in the heterozygous carriers of the insertion allele (15.1±9.2 mU/l) than in the subjects homozygous for the deletion allele (21.8±13.7 mU/l, P=0.0035). CONCLUSIONS: We were able to confirm the presence of a frequent insertion/deletion polymorphism close to the 3′-end of the leptin receptor gene. We also showed that serum insulin levels in morbidly obese subjects are associated with 3′-UTR variant genotype. [ABSTRACT FROM AUTHOR]

The article focuses on inflammation and cardiovascular disease. Several lipid-lowering trials have clearly established the importance of targeting LDL-cholesterol in order to reduce the risk of a first or recurrent coronary heart disease (CHD) event. A substantial proportion of CHD patients do not have LDL-cholesterol levels that are different from the healthy asymptomatic population, suggesting that there is a need to go beyond the lipid hypothesis and classical risk factors in order to properly assess and manage a significant proportion of high-risk individuals. Most studies have failed to properly control for abdominal fat accumulation when reporting the apparently independent association between CRP and the risk of myocardial infarction.