No abstract

Hepatic steatosis is commonly present during the development of insulin resistance, and it is a clear sign of lipotoxicity attributable in part to an accelerated lipogenesis. There is evidence that a soy protein diet prevents the overexpression of hepatic sterol-regulatory element binding protein-1 (SREBP-1), decreasing lipid accumulation. Therefore, the aim of the present work was to study whether a soy protein diet may prevent the development of fatty liver through the regulation of transcription factors involved in lipid metabolism in hyperinsulinemic and hyperleptinemic Zucker obese fa/fa rats. Serum and hepatic cholesterol and triglyceride levels, as well as VLDL-triglyceride and LDL-cholesterol, were significantly lower in rats fed soy protein than in rats fed a casein diet for 160 days. The reduction in hepatic cholesterol was associated with a low expression of liver X receptor-␣ and its target genes, 7-␣ hydroxylase and ABCA1. Obesity and associated diabetes are epidemic throughout the world. Obesity is the leading cause of insulin resistance and hyperinsulinemia, which predispose to glucose intolerance, diabetes, and cardiovascular diseases. As many as 40% of type 2 diabetics develop evidence of hepatic steatosis or fatty liver (1, 2).Several lines of evidence indicate that fatty liver in insulin-resistant states is caused by the activation of the sterolregulatory element binding protein-1c (SREBP-1c), which is increased in response to high insulin levels even in resistant states (3). SREBP-1c is a member of the family of SREBP membrane-bound transcription factors that activates mainly the transcription of genes involved in fatty acid synthesis (4). Thus, an increase in SREBP-1c expression increases the rate of lipogenesis in the liver (5). Analysis of the SREBP1c promoter has revealed an insulin-responsive region that maps to a binding site for liver X receptors (LXRs), suggesting a common pathway of action (6, 7).LXRs are nuclear hormone receptors that form active heterodimers with retinoid X receptors. They are activated by oxysterols and serve as key sensors of intracellular sterol levels by regulating the expression of genes that control cholesterol absorption, storage, transport, and elimination (8). Studies have demonstrated that the addition of the synthetic LXR ligand T0901317 increased the expression of SREBP-1c (9), indicating that these nuclear receptors provide interregulatory control of the cholesterol and fatty acid metabolism.Several studies in humans and experimental animals have demonstrated that the ingestion of soy protein reduces serum cholesterol and triglycerides (10-12). Furthermore, it has been shown that soy protein consumption also reduces the accumulation of cholesterol and triglycerides in the liver, preventing the development of fatty liver (13). There is evidence that soy protein regulates the concentration of serum and hepatic lipids by different mechanisms. We have demonstrated that rats fed a soy protein diet can control serum and hepatic lipid concentration b...

A diet rich in polyphenols can ameliorate some metabolic alterations associated with obesity and type 2 diabetes. Opuntia ficus-indica (OFI) is a plant rich in isorhamnetin glycosides and is highly consumed in Mexico. The purpose of this research was to determine the metabolic effect of an OFI extract on a mouse model of diet-induced obesity and in isolated pancreatic islets. OFI extract was added to a high fat (HF) diet at a low (0.3%) or high (0.6%) dose and administered to C57BL/6 mice for 12 weeks. Mice fed the HF diet supplemented with the OFI extract gained less body weight and exhibited significantly lower circulating total cholesterol, LDL cholesterol and HDL cholesterol compared to those fed the HF diet alone. The HF-OFI diet fed mice presented lower glucose and insulin concentration than the HF diet fed mice. However, the HF-OFI diet fed mice tended to have higher insulin concentration than control mice. The OFI extract stimulated insulin secretion in vitro, associated with increased glucose transporter 2 (GLUT2) and peroxisome proliferator-activated receptor gamma (PPARγ) mRNA content. Furthermore, the OFI extract improved glucose tolerance, and additionally increased energy expenditure. These metabolic improvements were associated with reduced adipocyte size, increased hepatic IRS1 tyr-608 and S6 K thr-389 phosphorylation. OFI isorhamnetin glycosides also diminished the hepatic lipid content associated with reduced mRNA expression of the endoplasmic reticulum stress markers and lipogenic enzymes and increased mRNA expression of genes related to fatty acid oxidation. Overall, the OFI extract prevented the development of metabolic abnormalities associated with diet-induced obesity.

The obese Zucker rat is a valuable model for studying kidney disease associated with obesity and diabetes. Previous studies have shown that substitution of animal protein with soy ameliorates the progression of renal disease. To explore the participation of nitric oxide (NO) and caveolin-1 in this protective effect, we evaluated proteinuria, creatinine clearance, renal structural lesions, nitrites and nitrates urinary excretion (UNO(2)(-)/NO(3)V), and mRNA and protein levels of neuronal NO synthase (nNOS), endothelial NOS (eNOS), and caveolin-1 in lean and fatty Zucker rats fed with 20% casein or soy protein diet. After 160 days of feeding with casein, fatty Zucker rats developed renal insufficiency, progressive proteinuria, and renal structural lesions; these alterations were associated with an important fall of UNO(2)(-)/NO(3)V, changes in nNOS and eNOS mRNA levels, together with increased amount of eNOS and caveolin-1 present in plasma membrane proteins of the kidney. In fatty Zucker rats fed with soy, we observed that soy diet improved renal function, UNO(2)(-)/NO(3)V, and proteinuria and reduced glomerulosclerosis, tubular dilation, intersticial fibrosis, and extracapilar proliferation. Renal protection was associated with reduction of caveolin-1 and eNOS in renal plasma membrane proteins. In conclusion, our results suggest that renal protective effect of soy protein appears to be mediated by improvement of NO generation and pointed out to caveolin-1 overexpression as a potential pathophysiological mechanism in renal disease.

Genistein is able to regulate the gut microbiota, reducing metabolic endotoxemia and decreasing the neuroinflammatory response despite the consumption of a HF diet.