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J Nutr Biochem. 2018 Jul;57:189-196. doi: 10.1016/j.jnutbio.2018.03.027. Epub 2018 Apr 7.

Dietary protein dilution limits dyslipidemia in obesity through FGF21-driven fatty acid clearance.

Author information

1
Joint Research Division Molecular Metabolic Control, German Cancer Research Center, Center for Molecular Biology, Heidelberg University and Heidelberg University Hospital, 69120 Heidelberg, Germany; Institute for Diabetes and Cancer (IDC), Helmholtz Center Munich, and Joint Heidelberg-IDC Translational Diabetes Program, Inner Medicine I, Heidelberg University Hospital, 85764 Neuherberg, Germany.
2
DKFZ Junior Group Metabolism and Stem Cell Plasticity, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
3
European Center for Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg University, and German Cancer Research Center (DKFZ-ZMBH Alliance), 69120 Heidelberg, Germany.
4
Division of Chronic Inflammation and Cancer, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
5
Joint Research Division Molecular Metabolic Control, German Cancer Research Center, Center for Molecular Biology, Heidelberg University and Heidelberg University Hospital, 69120 Heidelberg, Germany; Nutrient Metabolism and Signalling Lab, Dept. of Biochemistry and Molecular Biology, School of Biomedical Sciences, and Metabolism, Diabetes and Obesity Program, Biomedicine Discovery Institute, Monash University, Clayton, 3800, Australia. Electronic address: adam.rose@monash.edu.

Abstract

Recent studies have demonstrated that dietary protein dilution (PD) can promote metabolic inefficiency and improve glucose metabolism. However, whether PD can promote other aspects of metabolic health, such as improve systemic lipid metabolism, and mechanisms therein remains unknown. Mouse models of obesity, such as high-fat-diet-fed C57Bl/6 N mice, and New Zealand Obese mice were fed normal (i.e., 20%P) and protein-dilute (i.e., 5%EP) diets. FGF21-/- and Cd36-/- and corresponding littermate +/+ controls were also studied to examine gene-diet interactions. Here, we show that chronic PD retards the development of hypertrigylceridemia and fatty liver in obesity and that this relies on the induction of the hepatokine fibroblast growth factor 21 (FGF21). Furthermore, PD greatly enhances systemic lipid homeostasis, the mechanisms by which include FGF21-stimulated, and cluster of differentiation 36 (CD36) mediated, fatty acid clearance by oxidative tissues, such as heart and brown adipose tissue. Taken together, our preclinical studies demonstrate a novel nutritional strategy, as well as highlight a role for FGF21-stimulated systemic lipid metabolism, in combating obesity-related dyslipidemia.

KEYWORDS:

Diet; Fatty liver; Metabolism; Nutrition; Transport

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