osteum and Obesity

MicroRNAs are implicated as crucial mediators in metabolic diseases including obesity, diabetes, and non-alcoholic fatty liver diseases (NAFLD). Here, we show miR-27a attenuated hepatic de novo lipogenesis and alleviated obesity-initiated NAFLD through inhibiting Fasn and Scd1 in liver. Hepatic levels of miR-27a were significantly augmented in HFD-fed and ob/ob mice. Further studies demonstrated that miR-27a directly interacted with 3' untranslated region (3'-UTR) of hepatic Fasn and Scd1 mRNAs and reduced their expression levels in mice. Adenovirus-mediated overexpression of miR-27a robustly blocked sodium oleate-induced triglyceride (TG) accumulation in mouse primary hepatocytes and reduced liver TG contents in mice via repressing hepatic lipogenesis. Furthermore, ectopic expression of hepatic miR-27a impaired lipid contents of livers and attenuated NAFLD development through suppressing lipogenesis in HCD-fed and ob/ob mice. Together, our results reveal a critical role of miR-27a in lipid homeostasis of liver and pathogenesis of NAFLD.

Topics: Animals; Cells, Cultured; Diet, High-Fat; fas Receptor; Genetic Therapy; Hepatocytes; Lipid Metabolism; Lipogenesis; Liver; Male; Mice, Inbred C57BL; Mice, Obese; MicroRNAs; Non-alcoholic Fatty Liver Disease; Obesity; Oleic Acid; Primary Cell Culture; Stearoyl-CoA Desaturase; Triglycerides

Increased visceral fat accumulation is a strong predictor of arterial hypertension. In this study, we explored the hypothesis that increased hepatic portal venous free fatty acid delivery results in increased blood pressure. Such an effect might explain the link between visceral obesity and hypertension. In nine conscious, instrumented rats, we studied the effects of 1-hour infusions of sodium oleate solution into the portal and femoral veins and infusions of sodium caprylate solution into the portal vein on 3 separate days. Basal blood pressure was not significantly different on the 3 study days. Mean arterial pressure increased 29 +/- 4 mm Hg during portal oleate infusion and 13 +/- 2 mm Hg during femoral oleate infusion (both significant increases over basal, P < .001). Mean arterial pressure did not change during portal caprylate infusion. The increase during portal oleate infusion was greater than that during femoral oleate infusion (P = .028). Heart rate rose during all three infusions; the increase was greatest during portal oleate infusion (334 +/- 4 to 412 +/- 2 beats per minute). During portal venous oleate infusion in five rats, plasma norepinephrine rose from 2.17 +/- 0.34 to 3.58 +/- 0.50 nmol/L, epinephrine rose from 0.79 +/- 0.28 to 1.84 +/- 0.44 nmol/L, and corticosterone rose from 147 +/- 55 to 1130 +/- 289 nmol/L. Three rats given portal venous oleate infusions for 1 week had increased blood pressure compared with baseline (mean increase, 16 +/- 4 mm Hg). These studies indicate that increases in portal venous fatty acid concentrations have significant pressor effects, perhaps mediated by increased sympathetic tone.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Analysis of Variance; Animals; Antihypertensive Agents; Blood Glucose; Blood Pressure; Caprylates; Corticosterone; Epinephrine; Fatty Acids; Femoral Vein; Heart Rate; Hypertension; Infusions, Intravenous; Insulin; Liver Function Tests; Male; Norepinephrine; Obesity; Oleic Acid; Oleic Acids; Portal Vein; Radioimmunoassay; Rats; Rats, Sprague-Dawley; Renin; Time Factors; Triglycerides