Hypocaloric high-protein diet improves fatty liver and hypertriglyceridemia in sucrose-fed obese rats via two pathways.
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.
Department of Clinical Nutrition, University of Tokushima Graduate School, Tokushima, Japan.
Takashi
T
Uebanso
Yutaka
Y
Taketani
Makiko
M
Fukaya
Kazusa
K
Sato
Yuichiro
Y
Takei
Tadatoshi
T
Sato
Naoki
N
Sawada
Kikuko
K
Amo
Nagakatsu
N
Harada
Hidekazu
H
Arai
Hironori
H
Yamamoto
Eiji
E
Takeda
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D031204:Caloric Restriction; D002478:Cells, Cultured; D004038:Diet, Reducing / Q000379:methods; D004044:Dietary Proteins / Q000494:pharmacology / Q000627:therapeutic use*; D005215:Fasting / Q000097:blood / Q000378:metabolism; D005234:Fatty Liver / Q000178:diet therapy* / Q000209:etiology; D005247:Feeding Behavior / Q000187:drug effects / Q000502:physiology; D015228:Hypertriglyceridemia / Q000178:diet therapy* / Q000209:etiology; D008297:Male; D009765:Obesity / Q000139:chemically induced / Q000150:complications / Q000178:diet therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D013395:Sucrose
D001786:Blood Glucose; D004044:Dietary Proteins; D013395:Sucrose