Prevention and reversal of hepatic steatosis with a high-protein diet in mice

S. Garcia Caraballo, T.M. Comhair, F.K. Verheyen, I. Gaemers, F.G. Schaap, S.M. Houten, T.B. Hakvoort, C.H.C. Dejong, W.H. Lamers, S.E. Köhler*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

40 Citations (Web of Science)


The hallmark of NAFLD is steatosis of unknown etiology. We tested the high-protein (HP)(2) diet on diet-induced steatosis in male C57BL/6 mice without pre-existing fatty liver. Mice were fed all combinations of low-fat (LF) or high-fat (HF) and low-protein (LP) or HP diets for control for reduced energy intake by HF/HP-fed mice, a pair-fed HF/LP included. Reversibility of pre-existing steatosis was investigated by sequentially feeding HF/LP and HF/HP diets. HP-containing diets lipids to ~40% of corresponding LP-containing diets, were more efficient respect than reducing energy intake to 80%, and reversed pre-existing diet-induced steatosis. Compared to LP-containing diets, mice fed HP- diets showed increased mitochondrial oxidative capacity (elevated mAco, and Cpt1 mRNAs, complex-V protein, and decreased plasma free and short-chain acyl-carnitines, and [C0]/[C16+C18] carnitine ratio); gluconeogenesis and pyruvate cycling (increased PCK1 protein and fed plasma-glucose concentration without increased G6pase mRNA); reduced desaturation (decreased Scd1 expression and [C16:1n-7]/[C16:0] ratio) increased long-chain PUFA elongation; a selective increase in plasma branched-chain amino acids; a decrease in cell stress (reduced eIF2alpha, and Fgf21 and Chop expression); and a trend toward less (lower Mcp1 and Cd11b expression and less phosphorylated NFkappaB). HP diets prevent and reverse steatosis independently of fat and intake more efficiently than a 20% reduction in energy intake. The to result from fuel-generated, highly distributed small, synergistic lipid and BCAA catabolism, and a decrease in cell stress.
Original languageEnglish
Pages (from-to)685-695
JournalBiochimica et Biophysica Acta-Molecular Basis of Disease
Issue number5
Publication statusPublished - 1 Jan 2013

Cite this