Hypocaloric high-protein diet improves fatty liver and hypertriglyceridemia in sucrose-fed obese rats via two pathways

• Published in: American journal of physiology: endocrinology and metabolism 2009-07, Vol.297 (1), p.E76-E84
• Main Authors: Uebanso, Takashi, Taketani, Yutaka, Fukaya, Makiko, Sato, Kazusa, Takei, Yuichiro, Sato, Tadatoshi, Sawada, Naoki, Amo, Kikuko, Harada, Nagakatsu, Arai, Hidekazu, Yamamoto, Hironori, Takeda, Eiji
• Format: Article
• Language: English
• Subjects: Animals; Blood Glucose - metabolism; Caloric Restriction; Carbohydrates; Cells, Cultured; Correlation analysis; Diet; Diet, Reducing - methods; Dietary Proteins - pharmacology; Dietary Proteins - therapeutic use; Fasting - blood; Fasting - metabolism; Fatty Liver - diet therapy; Fatty Liver - etiology; Feeding Behavior - drug effects; Feeding Behavior - physiology; Gene expression; Hypertriglyceridemia - diet therapy; Hypertriglyceridemia - etiology; Lipids; Male; Metabolism; Obesity; Obesity - chemically induced; Obesity - complications; Obesity - diet therapy; Proteins; Rats; Rats, Sprague-Dawley; Rodents; Signal Transduction - drug effects; Sucrose
• ISSN: 0193-1849; 1522-1555
• DOI: 10.1152/ajpendo.00014.2009

1 Department of Clinical Nutrition; 2 Department of Nutrition and Metabolism, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima; and 3 Laboratory of Clinical Nutrition Management School of Food and Nutritional Sciences, University of Shizuoka, Shizuoka, Japan Submitted 7 January 2009 ; accepted in final form 6 May 2009 The mechanism by which replacement of some dietary carbohydrates with protein during weight loss favors lipid metabolism remains obscure. In this study, we investigated the effect of an energy-restricted, high-protein/low-carbohydrate diet on lipid metabolism in obese rats. High-sucrose-induced obese rats were assigned randomly to one of two energy-restricted dietary interventions: a carbohydrate-based control diet (CD) or a high-protein diet (HPD). Lean rats of the same age were assigned as normal control. There was significantly greater improvement in fatty liver and hypertriglyceridemia with the HPD diet relative to the CD diet. Expression of genes regulated by fibroblast growth factor-21 (FGF21) and involved in liver lipolysis and lipid utilitization, such as lipase and acyl-CoA oxidase, increased in obese rats fed the HPD. Furthermore, there was an inverse correlation between levels of FGF21 gene expression (regulated by glucagon/insulin balance) and increased triglyceride concentrations in liver from obese rats. Expression of hepatic stearoyl-CoA desaturase-1 (SCD1), regulated primarily by the dietary carbohydrate, was also markedly reduced in the HPD group (similar to plasma triglyceride levels in fasting animals) relative to the CD group. In conclusion, a hypocaloric high-protein diet improves fatty liver and hypertriglyceridemia effectively relative to a carbohydrate diet. The two cellular pathways at work behind these benefits include stimulation of hepatic lipolysis and lipid utilization mediated by FGF21 and reduction of hepatic VLDL-TG production by SCD1 regulation. calorie restriction; fibroblast growth factor-21; stearoyl-CoA desaturase-1 Address for reprint requests and other correspondence: Y. Taketani, Dept. of Clinical Nutrition, School of Medicine, Univ. of Tokushima, 3-18-15, Kuramoto, Tokushima 770-8503, Japan (e-mail: taketani{at}nutr.med.tokushima-u.ac.jp )