TY - JOUR
T1 - Prevention and reversal of hepatic steatosis with a high-protein diet in mice
AU - Garcia Caraballo, S.
AU - Comhair, T.M.
AU - Verheyen, F.K.
AU - Gaemers, I.
AU - Schaap, F.G.
AU - Houten, S.M.
AU - Hakvoort, T.B.
AU - Dejong, C.H.C.
AU - Lamers, W.H.
AU - Köhler, S.E.
PY - 2013/1/1
Y1 - 2013/1/1
N2 - 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.
AB - 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.
U2 - 10.1016/j.bbadis.2013.02.003
DO - 10.1016/j.bbadis.2013.02.003
M3 - Article
C2 - 23410526
SN - 0925-4439
VL - 1832
SP - 685
EP - 695
JO - Biochimica et Biophysica Acta-Molecular Basis of Disease
JF - Biochimica et Biophysica Acta-Molecular Basis of Disease
IS - 5
ER -