Overweight and obesity, if sustained, are serious medical problems reaching an epidemic proportion. It is estimated that over 55% of the adult population is affected by overweight and obesity. Both overweight and obesity put these individuals at a high risk for the development of insulin resistance, hypertension, dyslipidemia, type 2 diabetes and coronary heart disease. A weight loss of between 5% and 10% of the initial body weight has been shown to greatly reduce these health risks associated with overweight and obesity. Typically, the first-line clinical strategy for weight loss is a combination of supervised diet, exercise and behavior modification. Although life style modification can exert beneficial effects in overweighed and obese individuals, it is difficult to achieve and maintain weight losses solely by life style change. Anti-obesity drugs may be used in obese patients (BMI of 30 or greater), or overweight patients with established comorbidities (BMI > 27), where dietary and lifestyle modifications are unsuccessful in achieving a 10% weight reduction following at least three months of the supervised care. Current anti-obesity drug therapy is geared towards reducing energy/food intake via actions on either gastrointestinal system or the central control of appetite and feeding. A thorough understanding of the molecular pathways involved in weight gain and appetite suppression should help for a better drug design and development. This mini review will focus on the molecular mechanisms and currently available pharmacotherapeutic interventions in overweight and obesity.

Background: The Indian spice fenugreek (Trigonella foenum-graecum) has been credited with numerous health benefits in cardiovascular disorders, metabolic syndrome, inflammatory conditions, glucose-insulin regulation, and sports performance. Previous studies from our laboratories demonstrated that fenugreek seed extract improved glucose tolerance, insulin sensitivity, augmented serum testosterone level and improved cardiovascular functions. Our investigation examined the efficacy of Furosap, a novel fenugreek seed extract enriched in 20% protodioscin, on exercise performance. Methods: This randomized, double-blind, placebo-controlled, clinical study was conducted in forty healthy male athletes (n = 40) over a period of 12 consecutive weeks. Subjects were given either placebo or Furosap capsules (250 mg/day b.d.) and serum samples were used to assess serum total testosterone level and C-reactive proteins (CRP) at baseline and at the end of 12-weeks of treatment. Body fat mass, lean mass, fat mass, fat-free mass, grip strength, upper and lower body strength, maximal graded exercise stress using a digital hand dynamometer, dual-energy X-ray absorptiometry (DEXA), force plate, and treadmill with open-circuit spirometry were assessed at the baseline and at the end of 12-weeks of treatment.Results: Furosap supplementation significantly increased mean lean body mass and fat-free mass compared to subjects receiving placebo. Additionally, Furosap-treated subjects elevated serum testosterone levels. Furosap supplemented subjects also exhibited a tendency towards lowering blood pressure during exhaustion. No adverse reports were reported.Conclusions: Given improvement of lean body mass and serum total testosterone following intervention with Furosap, Furosap likely has benefits for exercise endurance and sports medicine. Keywords: Fenugreek seed extract; safety; body mass; fat-free mass; blood pressure; muscle strength.

Collectively, our data suggest that fenugreek furostanolic saponins and green coffee bean extract may have potential benefits in treating insulin resistance and related conditions.

Impaired digestive competence and consequential sluggish immune and metabolic sequela are epidemic‐sized health problems in modern cultures. Since digestion is the first step of metabolism, implementing novel strategies to restore digestive and metabolic competence are important health priorities. N‐SORB is a patent‐pending KD120 multienzyme complex composed of metabolically activated natural digestive‐type enzymes encapsulated in a high‐potency phosphatidylcholine non‐GMO soy lecithin SK713 SLP absorption technology (Prodosome®). A randomized, double‐blind placebo‐controlled study was conducted in 46 male and female healthy volunteers (age: 25.8 ± 12.1 years) to assess the safety and efficacy of N‐SORB. Subjects received either N‐SORB (1 mL, twice daily) or the same amount of placebo for 90 consecutive days. Body weight, blood pressure, physical health, and complete blood chemistries including blood glucose, liver enzymes, and lipid profiles; and immune health, physical health, sleep quality and quality of life parameters were assessed pre‐ and post‐intervention. Serum cytokine levels were determined by using a Bio‐Plex Pro Human Cytokine 8‐plex assay and ELISA. Whole body composition analysis was performed by dual‐energy X‐Ray absorptiometry (DEXA) to determine body fat mass, lean mass and android and gynoid fat. Quality of life (QOL) and sleep quality were assessed using WHOQOL‐BREF and Pittsburgh Sleep Quality Index (PSQI) questionnaire. Adverse events were strictly monitored. 40 subjects completed the study. Hematocrit, hemoglobin, mean corpuscular volume, platelets and lymphocytes provide evidence indicating consistent trends of improvement in the N‐SORB group. QOL parameters showed a small but significant improvement in the N‐SORB group. A significant increase was observed in AST levels in the placebo group at the end of 90 days of treatment, indicating increased liver distress. However, no increase was observed in the N‐SORB group. No significant changes in BUN, serum creatinine, ALP, ALT, and lipid profile were observed between the placebo and treatment groups before and after the 90‐day intervention. No adverse effects were reported. This 90‐day intervention study with N‐SORB clearly exhibited trends of improvement in RBC and immune parameters and found improvements in QOL and sleep quality scivnin already healthy volunteers. The N‐SORB treatment group experienced significant improvement in gastrointestinal functions, immune and metabolic parameters and other systemic improvements. No adverse events were reported. Support or Funding Information The Project was partially sponsored by VNI Inc, Lederach, PA

BackgroundType 2 Diabetes Mellitus (T2DM) is growing at epidemic proportions worldwide. Insulin resistance, defined as an impaired responsiveness of the body to insulin, is a pre‐diabetic stage in the transition from obesity to full‐blown diabetes. Recent studies from our lab demonstrated that furostanolic saponins (FS) isolated from the spice fenugreek improved glucose tolerance and reduced hepatic steatosis in high‐fat diet‐fed, obese mice.ObjectiveThe objective of this study was to evaluate the effect of supplementation of fenugreek FS on cardiometabolic parameters in insulin resistant, obese subjects.MethodsThis was a single center, double‐blind, randomized, placebo‐controlled, parallel‐arm, pilot study in overweight/obese (body mass index>25Kg/m2) young (mean age 27.1±6.1y), otherwise healthy, male and female subjects who satisfied any two of the following three inclusion criteria: i) hemoglobin A1c >5.6% ii) a two‐hour post‐glucose challenge blood‐glucose level > 125 mg/dL and iii) Homeostatic Model Assessment‐insulin resistance (HOMA‐IR) value of >2.5 (fasting insulin (microU/L) x fasting glucose (nmol/L)/22.5). Following informed consent, health‐screening and satisfaction of the inclusion/exclusion criterial, 28‐participants were randomly assigned to receive either placebo (microcrystalline cellulose) or FS (500 mg twice daily) capsules for a period of 12‐weeks. Anthropometric measurements, blood pressure, fasting blood glucose, fasting serum insulin, hemoglobin A1c, lipids, ALT, AST, C‐reactive proteins were determined at baseline and following 12‐week intervention. Body fat composition was determined by dual energy X‐ray absorptiometry. Serum cytokine levels were determined by a Bio‐Plex Pro Human Cytokine 8‐Plex assay. Data were analyzed by a nonparametric bootstrap analysis and the difference of simulated data from treatment and placebo were compared to test for significance. All runs were included in the calculation of 95% confidence interval.ResultsOf the 28 recruited, 25 subjects completed the study. No adverse events were reported, except for one subject who dropped form the study complaining of mild stomach discomfort. No changes were observed between pre‐ and post‐intervention in mean body mass, systolic or diastolic blood pressure, fasting glucose, hemoglobin A1c, lipid‐panel, serum transaminases, and cytokine levels in subjects receiving either the placebo or FS. In contrast, a significant reduction in HOMA‐IR was observed in subjects who received FS compared to those who received the placebo. Additionally, a trend towards lowering of serum insulin levels was observed in the group that received FS.ConclusionTwelve‐week supplementation with fenugreek saponins resulted in reduction in markers of insulin resistance in obese, insulin‐resistant subjects, warranting future studies with FS in overt‐diabetic subjects.Support or Funding InformationSupported by the NIH through the National Institute of General Medical Sciences (NIGMS) #1U54GM104944‐01A1 under the Institutional Development Award (IDeA) program.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.