Ameliorative effects of zinc supplementation on cognitive function and hippocampal leptin signaling pathway in obese male and female rats.

Obesity has been associated with cognitive impairments, increasing the probability of developing dementia. Recently, zinc (Zn) supplementation has attracted an increasing attention as a therapeutic agent for cognitive disorders. Here, we investigated the potential effects of low and high doses of Zn supplementation on cognitive biomarkers and leptin signaling pathway in the hippocampus of high fat diet (HFD)-fed rats. We also explored the impact of sex difference on the response to treatment. Our results revealed a significant increase in body weight, glucose, triglycerides (TG), total cholesterol (TC), total lipids and leptin levels in obese rats as compared to controls. HFD feeding also reduced brain-derived neurotrophic factor (BDNF) levels and increased acetylcholinesterase (AChE) activity in the hippocampus of both sexes. The low and high doses of Zn supplementation improved glucose, TG, leptin, BDNF levels and AChE activity in both male and female obese rats compared to untreated ones. Additionally, downregulated expression of leptin receptor (LepR) gene and increased levels of activated signal transducer and activator of transcription 3 (p-STAT3) that observed in hippocampal tissues of obese rats were successfully normalized by both doses of Zn. In this study, the male rats were more vulnerable to HFD-induced weight gain, most of the metabolic alterations and cognition deficits than females, whereas the female obese rats were more responsive to Zn treatment. In conclusion, we suggest that Zn treatment may be effective in ameliorating obesity-related metabolic dysfunction, central leptin resistance and cognitive deficits. In addition, our findings provide evidence that males and females might differ in their response to Zn treatment.

The Anti-Obesity and Anti-Steatotic Effects of Chrysin in a Rat Model of Obesity Mediated through Modulating the Hepatic AMPK/mTOR/lipogenesis Pathways.

BACKGROUND: Obesity is a complex multifactorial disease characterized by excessive adiposity, and is linked to an increased risk of nonalcoholic fatty liver disease (NAFLD). Flavonoids are natural polyphenolic compounds that exert interesting pharmacological effects as antioxidant, anti-inflammatory, and lipid-lowering agents. In the present study, we investigated the possible therapeutic effects of the flavonoid chrysin on obesity and NAFLD in rats, and the role of AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathways in mediating these effects. METHOD: Thirty-two Wistar male rats were divided into two groups: the control group and the obese group. Obesity was induced by feeding with an obesogenic diet for 3 months. The obese rats were subdivided into four subgroups, comprising an untreated group, and three groups treated orally with different doses of chrysin (25, 50, and 75 mg/kg/day for one month). Results revealed that chrysin treatment markedly ameliorated the histological changes and significantly and dose-dependently reduced the weight gain, hyperglycemia, and insulin resistance in the obese rats. Chrysin, besides its antioxidant boosting effects (increased GSH and decreased malondialdehyde), activated the AMPK pathway and suppressed the mTOR and lipogenic pathways, and stimulated expression of the genes controlling mitochondrial biogenesis in the hepatic tissues in a dose-dependent manner. In conclusion, chrysin could be a promising candidate for the treatment of obesity and associated NAFLD, aiding in attenuating weight gain and ameliorating glucose and lipid homeostasis and adipokines, boosting the hepatic mitochondrial biogenesis, and modulating AMPK/mTOR/SREBP-1c signaling pathways.

Effect of short-term high fat diet on resistin levels and expression of autophagy-related genes in the cartilage of male rats.

Obesity is a significant risk factor for the development of knee osteoarthritis (KOA). However, the precise molecular mechanisms linking obesity to OA remain unclear. In the present study, we investigated the effect of short-term high-fat diet (HFD) on the development of OA and the possible role of the adipokine resistin and autophagy-related genes in mediating this effect. Thirty adult male Wistar rats were equally divided into 2 groups: control and obese groups. Body mass index (BMI), levels of lipid profile, glucose, insulin and HOMA-IR index were significantly higher in the obese group compared with control. Our results revealed significantly higher serum and cartilage resistin levels with a significant increase in the mRNA expressions of toll-like receptor 4 (TLR4), matrix metalloproteinase-9 (MMP-9) and interleukin-1ß (IL-1ß) as well as protein levels of IL-1ß, matrix metalloproteinase-13 (MMP-13), ADAMTS 5 (aggrecanase-2) and caspase-3 in the cartilage of obese rats. The HFD induced a significant upregulation of autophagy related 5 (ATG5), beclin-1 and light chain 3 (LC3) mRNA expressions and a significant downregulation of mammalian target of rapamycin (mTOR) expression in cartilage. The protein levels of cartilage ATG5 were also significantly elevated in HFD-fed group. In conclusion, we suggested that increased levels of resistin and expression of autophagy-related genes may contribute in part, to OA development in HFD-fed rats. This provides a novel insight into the early molecular changes in the cartilage associated with obesity.