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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]

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]

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]

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]

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]