It is also possible that there is a temporal dissociation between steatosis and insulin resistance, so that IHTG accumulation is secondary to a primary defect in skeletal muscle insulin action by diverting ingested carbohydrates away from muscle glycogen storage to DNL.36 Calorie restriction and weight loss is an effective therapy for obese patients with NAFLD. A marked decrease in IHTG content and improvement in hepatic insulin sensitivity occurs very rapidly, within 48 hours of calorie restriction (≈1,100 kcal/day diet).88 A comprehensive

review of 14 studies that evaluated the effect of lifestyle weight loss therapy on NAFLD/nonalcoholic

steatohepatitis,89 and data from recent prospective diet intervention studies,88, 90 found that a 5% to 10% weight loss X-396 nmr improved liver biochemistries, liver histology CHIR99021 (steatosis and inflammation), and IHTG content in conjunction with an increase in hepatic and skeletal muscle insulin sensitivity and a decrease in hepatic VLDL-TG secretion rate.91 Bariatric surgery is the most effective available weight loss therapy. There has been concern that the large and rapid weight loss, induced by bariatric surgery, can actually worsen NAFLD by increasing hepatic inflammation and fibrosis.92 However, data from more recent surgical series suggest that weight loss induced by bariatric surgery decreases steatosis, inflammation, and fibrosis.93, 94 In addition, bariatric surgery induced weight loss has considerable

beneficial metabolic effects in the liver manifested by a decrease in (1) hepatic glucose production, (2) hepatic VLDL-triglyceride secretion rate, and (3) hepatic gene expression of factors that regulate hepatic inflammation and fibrogenesis.95 These data suggest that bariatric surgery–induced weight loss is an effective therapy for NAFLD in patients with morbid obesity by normalizing the metabolic abnormalities involved in the pathogenesis and pathophysiology of NAFLD and by preventing the progression of hepatic inflammation 上海皓元医药股份有限公司 and fibrosis. The effect of overfeeding on IHTG content and metabolic function has not been carefully studied in human subjects. Data from a study conducted in rodents suggest that overfeeding first has a metabolic effect on the liver followed by an effect on muscle; insulin resistance in the liver was observed after 3 days and in muscle after 7 days of overfeeding.96 Four weeks of overfeeding in lean men and women, designed to cause a 5% to 15% increase in body weight, resulted in a significant increase in IHTG content (from 1.1% to 2.