Insulin resistance (IR) is a state characterized by the inability of tissues to utilize blood glucose particularly liver, muscle, and adipose tissues resulting in hyperglycemia and hyperinsulinemia. A close relationship exists between IR and the development of type 2 diabetes (T2D). Therefore, therapeutic approaches to treat IR also improve T2D simultaneously. Scientific evidence has highlighted the major role of inflammatory cytokines, reactive oxygen species (ROS), environmental & genetic factors, and auto-immune disorders in the pathophysiology of IR. Among therapeutic remedies, nutraceuticals like polyphenols are being used widely to ameliorate IR due to their safer nature compared to pharmaceutics. Stilbenes are considered important metabolically active polyphenols currently under the limelight of research to cope with IR. In this review, efforts are made to elucidate cellular and subcellular mechanisms influenced by stilbenes including modulating insulin signaling cascade, correcting glucose transport pathways, lowering postprandial glucose levels, and protecting β-cell damage and its effects on the hyperactive immune system and proinflammatory cytokines to attenuate IR. Furthermore, future directions to further the research in stilbenes as a strong candidate against IR are included so that concrete recommendation for their use in humans is made.

The abusive consumption of thermogenic supplements occurs worldwide and deserves special attention due to their use to stimulate weight loss and prevent obesity. Thermogenic formulations usually contain Synephrine (SN) and Caffeine (CAF), stimulating compounds extracted from natural sources, but no genetic toxicology studies have predicted this hazardous combination potential. This study examined the toxicogenomic responses induced by SN and CAF, either alone or in combination, in the human hepatic cell line HepG2 in vitro. SN (0.03-30 μM) and CAF (0.6-600 μM) alone did neither decrease cell viability nor induce DNA damage, as assessed using the MTT and comet assays, respectively. SN (3 μM) and CAF (30-600 μM) were combined at concentrations similar to those found in commercial dietary supplements. SN/CAF at 3:90 and 3:600 μM ratios significantly decreased cell viability and increased DNA damage levels in HepG2 cells. CAF (600 μM) and the SN/CAF association at 3:60, 3:90, and 3:600 μM ratios promoted cell death by apoptosis, as demonstrated by flow cytometry. Similar results were observed in gene expression (RT-qPCR): SN/CAF up-regulated the expression of apoptosis- (BCL-2 and CASP9) and DNA repair-related (XPC) genes. SN/CAF at 3:90 μM also downregulated the expression of cell cycle control (CDKN1A) genes. In conclusion, the SN/CAF combination reduces cell viability by inducing apoptosis, damages DNA, and modulates the transcriptional expression of apoptosis-, cell cycle-, and DNA repair-related genes in human hepatic (HepG2) cells in vitro. These effects can be worrisome to consumers of thermogenic supplements.

Leptin resistance and co-existing insulin resistance is considered as hallmark of diet-induced obesity. Here, we investigated therapeutic potential of hesperidin to improve leptin and insulin resistance using high fat diet (HFD)-induced obese experimental animal model. We also performed in silico studies to validate therapeutic effectiveness of hesperidin by performing protein-ligand docking and molecular dynamics simulation studies. Group 1 was identified as control group receiving vehicle only. Group 2 was marked as non-treated group receiving 60% HFD. While, other groups were treated daily with orlistat (120 mg/kg/d), hesperidin (55 mg/kg/d), combination of hesperidin (55 mg/kg/d) + orlistat (120 mg/kg/d). Hesperidin alone (P<0.001) and particularly in combination with orlistat (P<0.001), resulted in controlling the levels of HFD-altered biomarkers including random and fasting state of glycemia, leptin and insulin resistance. Similarly, hesperidin also improved the serum and tissue levels of leptin, interleukin-6 and tumor necrosis factor-alpha more significantly (P<0.05) when compared with that of orlistat. These results were found to be in accordance with the results of histopathological examination of pancreas, liver and adipose tissues. In-silico studies also proved that hesperidin binds to leptin receptor with higher affinity as compared to that of orlistat and induces the favorable variations in geometrical conformation of leptin receptor to promote its association with leptin which may lead to the cascades of reactions culminating the lipolysis of fats that may ultimately lead to cure obesity. The results of this study may be a significant expectation among the forthcoming treatment strategies for leptin and insulin resistance.

Despite high prevalence of nonalcoholic fatty liver disease in China, understanding of the disease appears to be low.

We assessed the knowledge of NAFLD among the public in Beijing, China, as well as diet and physical activity patterns, which may provide information useful for NAFLD prevention and management.

We surveyed adult patients and family members in the Peking University Health Science Center (PUHSC) ultrasound clinic and office staff in Beijing, China. Participants provided demographic and medical history data. NAFLD-related knowledge and diet and physical activity were assessed.

A total of 1296 participants at the PUHSC clinic (51% female, median age 35, 61% college-educated) and 494 participants in offices (61% female, median age 43, 74% college-educated) completed the survey. Response rate was 68.4% and 96.7%, respectively. In clinic and offices, 44% versus 48% were overweight/obese, 5% had a history of diabetes in both groups, and 14% versus 23% had a personal history of NAFLD. Median knowledge score was 15 out of 25 in clinic versus 16 in offices. 44.9% reported minimal physical activity. Factors associated with higher NAFLD knowledge scores (> 16) on multivariate analysis included college education or higher (OR 1.7, p = 0.01), family history of hyperlipidemia (OR 1.96, p < 0.001), and number of sugary drinks per week (OR 0.74, p = 0.006). No factors were significantly associated with physical activity levels.

Adults in Beijing had low knowledge about NAFLD, and most were not physically active. Programs to increase public awareness of NAFLD and promote physical activity are critical to curb this growing epidemic.