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.