Daidzein supplementation prevents non-alcoholic fatty liver disease through alternation of hepatic gene expression profiles and adipocyte metabolism.

INTRODUCTION: Globally, non-alcoholic fatty liver disease (NAFLD) continues to rise and isoflavones exert antisteatotic effects by the regulation of hepatic lipogenesis/insulin resistance or adiposity/a variety of adipocytokines are related to hepatic steatosis. However, there is very little information regarding the potential effects of daidzein, the secondary abundant isoflavone, on NAFLD. Here, we have assessed the hepatic global transcription profiles, adipocytokines and adiposity in mice with high fat-induced NAFLD and their alteration by daidzein supplementation. METHODS: C57BL/6J mice were fed with normal fat (16% fat of total energy), high fat (HF; 36% fat of total energy) and HF supplemented with daidzein (0.1, 0.5, 1 and 2 g per kg diet) for 12 weeks. RESULTS: Daidzein supplementation (≥ 0.5 g per kg diet) reduced hepatic lipid concentrations and alleviated hepatic steatosis. The hepatic microarray showed that daidzein supplementation (1 g per kg diet) downregulated carbohydrate responsive element binding protein, a determinant of de novo lipogenesis, its upstream gene liver X receptor ß and its target genes encoding for lipogenic enzymes, thereby preventing hepatic steatosis and insulin resistance. These results were confirmed by lower insulin and blood glucose levels as well as homeostasis model assessment insulin resistance scores. In addition, daidzein supplementation inhibited adiposity by the upregulation of genes involved in fatty acid ß-oxidation and the antiadipogeneis, and moreover augmented antisteatohepatitic leptin and adiponectin mRNA levels, whereas it reduced the mRNA or concentration of steatotic tumor necrosis factor α and ghrelin. CONCLUSIONS: These findings show that daidzein might alleviate NAFLD through the direct regulation of hepatic de novo lipogenesis and insulin signaling, and the indirect control of adiposity and adipocytokines by the alteration of adipocyte metabolism.

Effects of autonomic drugs on the cardiovascular system: dogs with achalasia (under halothane anesthesia).

The parasympathetic and sympathetic components of the autonomic systems as they relate to cardiovascular function were studied on dogs with achalasia of the esophagus. This was accomplished by administering the parasympathomimetic drugs methacholine (0.2 mg/kg, subcutaneously), 2 doexy-D-glucose (100 mg/kg, intravenously (IV), the parasympatholytic drug atropine (0.2 mg/kg, IV), the sympathomimetic agent epinephrine (2.5 microng/kg, IV), and the beta adrenergic blocker propranolol (0.5 mg/kg, IV); and then measuring cardiac output, stroke volume, heart rate, mean arterial pressure, pulse pressure, central venous pressure, total peripheral resistance, PaCO2, PaO2, pH, and base deficit. Cardiovascular responses to the administration of the parasympathomimetic drugs, methacholine and 2 deoxy-D-glucose, or the parasympatholytic drug, atropine, were similar to those observed in normal dogs. Cardiovascular responses to the administration of the sympathomimetic drug epinephrine and the sympatholytic drug propranolol or beta blocker were also consistent with those observed in normal dogs. It can be interpreted from this pharmacologic evidence that parasympathetic and sympathetic innervations to the cardiovascular system are present in dogs with achalasia of the esophagus. Fewer cardiovascular variables were significantly altered in dogs with achalasia than in normal dogs. Since this was true for both the sympathetic and the parasympathetic values, it is interpreted as reflecting their general health rather than a specific lesion.