Objective: The present study was undertaken to explore the effect of piperine in obesity-induced dyslipidemia. Materials and Methods: Male Sprague Dawley rats were fed high-fat diet (HFD) for the first eight weeks, to develop obesity-induced dyslipidemia. Later on piperine (40 mg / kg) and sibutramine (5 mg / kg) were administered for three weeks along with the continuation of HFD to two separate groups, which served as the test and standard groups, respectively. Body weight, food intake, serum triglyceride, total cholesterol, LDL, VLDL, and HDL were measured at the end of the fourth, eighth (before treatment), and eleventh (after treatment) week, while the fat mass was measured at the end of the eleventh week in the normal, HFD-control, test, and standard groups. Results: Supplementing piperine with HFD significantly reduced not only body weight, triglyceride, total cholesterol, LDL, VLDL, and fat mass, but also increased the HDL levels, with no change in food intake. Conclusion: The above results suggest that piperine possesses potential fat reducing and lipid lowering effects, without any change in food appetite, at a small dose of 40 mg / kg. The mechanism of action for such an activity needs to be determined. However, looking to structural similarity with the presently known Melanocortin-4 (MC-4) agonists, involvement of MC-4 receptors in its activity can be guessed.

Polycystic ovary syndrome (PCOS) is associated with hyperandrogenism, oligo-anovulation, polycystic ovaries and metabolic syndrome. Many researchers reported that PCOS often starts with menarche in adolescents. Presently available animal model focuses on ovarian but not metabolic features of PCOS. Therefore, we hypothesized that high-fat diet feeding to pre-pubertal female rats results in both reproductive and metabolic features of PCOS. Pre-pubertal female rats were divided into two groups: group I received normal pellet diet and group II received high-fat diet (HFD). In the letrozole study, adult female rats were divided into two groups: group I received 1% carboxy methyl cellulose and group II received 1 mg/kg letrozole orally. Oral glucose tolerance test, lipid profile, fasting glucose, insulin, estrus cycle, hormonal profile, ovary weight, luteinizing hormone (LH) receptor and follicle-stimulating hormone receptor expression were measured. Polycystic ovarian morphology was assessed through histopathological changes of ovary. Feeding of HFD gradually increase glucose intolerance and fasting insulin levels. Triglyceride level was higher in HFD study while total cholesterol level was higher in the letrozole study. Alteration in testosterone and estrogen levels was observed in both studies. LH receptor expression was upregulated only in HFD study. Histopathological changes like increase cystic follicle, diminished granulosa cell layer and thickened theca cell layer were observed in letrozole as well as HFD study. High-fat diet initiated at pre-puberty age in rats produces both metabolic disturbances and ovarian changes similar to that observed clinically in PCOS patients. Letrozole on the other hand induces change in ovarian structure and function.

Glucagon-like peptide-1 (GLP-1), is a hormone secreted by small intestine. Consumption of food or glucose stimulates synthesis and secretion of GLP-1 in the bloodstream, which in turn stimulates insulin secretion from pancreas and delays gastric emptying. Owing to the favorable spectrum of effects on reduction of hyperglycemia and body weight, GLP-1 mimetics are intensely pursued as therapies for the treatment of type 2 diabetes (T2DM). Even after intensive control of hyperglycemia, the propensity for cardiovascular disease cannot be totally negated in diabetic patients. A major reason for the cardiovascular disease risk in diabetic patients is underlying dyslipidemia, also termed as diabetic dyslipidemia. It is characterized by high concentrations of triglycerides and LDL cholesterol, and lowered HDL cholesterol in plasma, which are associated with hyperglycemia. Increased insulin resistance gives rise to increased free fatty acids in bloodstream, which is the main reason for the lipid changes appearing in diabetic dyslipidemia. The secondary complications like atherosclerosis and other cardiovascular diseases may be predicted with the blood concentrations of triglycerides and cholesterol, due to the correlation proven in clinic. Hence, new drugs that target diabetic dyslipidemia will always be useful in therapy. Apart from its actions on body weight and glucose, GLP-1 can also regulate cholesterol and triglycerides by numerous ways. Acute and long term treatment with either GLP-1 or its stable analogs reduced fasting as well as postprandial lipids in healthy as well as T2DM patients. GLP-1R signaling reduces VLDL-TG production rate from liver, reduces hepatic TG content by modulating key enzymes of lipid metabolism in liver, and impairs hepatocyte de novo lipogenesis and β-oxidation. GLP-1 can also modulate reverse cholesterol transport. Apart from these direct effects on lipid metabolism, GLP-1 also reduces atherosclerotic events by inhibiting expression of atherogenic inflammatory mediators, suppressing smooth muscle cell proliferation and stimulating NO production. This review mainly deliberates the association of GLP-1 in lipid regulation via lipid absorption, hepatic cholesterol metabolism, reverse cholesterol transport and progression of atherosclerosis.

Objective: Metformin has been used as a treatment option for polycystic ovary syndrome (PCOS) since 1994; however, more than a hundred randomized clinical trials have reported controversial results regarding the efficacy of metformin in PCOS. This could be due to the small sample size and high variability in methodology between studies. The objective of the present meta-analysis was to determine the effect of metformin on clinical, metabolic, and endocrine outcomes compared to placebo in PCOS women. Methods: Randomized controlled trials evaluating the efficacy of metformin were identified using a literature search in PubMed. Bibliographies of relevant studies were also screened to identify additional studies. Data was extracted from included studies and analyzed using RevMan software 5.3 from the Cochrane Collaboration. Main outcome measures: Clinical outcomes included body mass index, waist to hip ratio, systolic and diastolic blood pressure and Ferriman–Gallway score. Metabolic outcomes included total cholesterol, triglycerides, low-density lipoprotein, high-density lipoprotein, very low-density lipoprotein, fasting blood glucose, fasting insulin levels, glucose insulin ratio, HOMA-IR and QUICKI. Endocrine outcomes such as serum testosterone, free testosterone, free androgen index, serum sex hormone binding globulin, dehydroepiandrosterone sulfate, luteinizing hormone, follicle stimulating hormone, LH/FSH ratio, estradiol, and progesterone levels. Conclusion: Metformin showed significant improvement in clinical outcomes but not in metabolic and endocrine outcomes in PCOS women; however, heterogeneity between studies was found to be moderate to high.