Submitted on January 7, 2009
Revised on April 20, 2009
Accepted on May 6, 2009
Hypocaloric high protein diet improves fatty liver and hypertriglyceridemia in sucrose-fed obese rats via two pathways
Takashi Uebanso1, Yutaka Taketani2*, Makiko Fukaya3, Kazusa Sato2, Yuichiro Takei4, Tadatoshi Sato2, Naoki Sawada2, Kikuko Amo2, Nagakatsu Harada1, Hidekazu Arai5, Hironori Yamamoto6, and Eiji Takeda4
1 University of Tokushima
2 University of Tokushima, School of Medicine
3 University of Tokushima School of Medicine
4 University of Tokushima Graduate School
5 The University of Shizuoka School of Food and Nutritional Sciences
6 University Tokushima School of Medicine
* To whom correspondence should be addressed. E-mail: taketani{at}nutr.med.tokushima-u.ac.jp.
The mechanism by which replacement of some dietary carbohydrate 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.
