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Am J Physiol Endocrinol Metab. 2016 Jun 1;310(11):E886-99. doi: 10.1152/ajpendo.00363.2015. Epub 2016 Mar 29.

Effect of a long-term high-protein diet on survival, obesity development, and gut microbiota in mice.

Author information

1
Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, Copenhagen, Denmark;
2
Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, Copenhagen, Denmark; National Institute of Nutrition and Seafood Research, Bergen, Norway;
3
Top Institute Food and Nutrition, Wageningen, The Netherlands;
4
National Food Institute, Technical University of Denmark, Søborg, Denmark;
5
Department of Veterinary Disease Biology, University of Copenhagen, Copenhagen, Denmark; Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, University of Copenhagen, Denmark;
6
National Research Centre for the Working Environment, Copenhagen, Denmark;
7
National Institute of Nutrition and Seafood Research, Bergen, Norway;
8
BGI-Shenzhen, Shenzhen, China.
9
Top Institute Food and Nutrition, Wageningen, The Netherlands; Host Microbe Interactomics Group, Wageningen University, Wageningen, The Netherlands;
10
Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, Copenhagen, Denmark; BGI-Shenzhen, Shenzhen, China, Princess Al Jawhara Albrahim Center of Excellence in the Research of Hereditary Disorders, King Abdulaziz University, Jeddah, Saudi Arabia; Macau University of Science and Technology, Taipa, Macau, China; Department of Medicine and State Key Laboratory of Pharmaceutical Biotechnology, University of Hong Kong, Hong Kong, China.
11
Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, Copenhagen, Denmark; National Institute of Nutrition and Seafood Research, Bergen, Norway; BGI-Shenzhen, Shenzhen, China.
12
Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, Copenhagen, Denmark; BGI-Shenzhen, Shenzhen, China, kk@bio.ku.dk.

Abstract

Female C57BL/6J mice were fed a regular low-fat diet or high-fat diets combined with either high or low protein-to-sucrose ratios during their entire lifespan to examine the long-term effects on obesity development, gut microbiota, and survival. Intake of a high-fat diet with a low protein/sucrose ratio precipitated obesity and reduced survival relative to mice fed a low-fat diet. By contrast, intake of a high-fat diet with a high protein/sucrose ratio attenuated lifelong weight gain and adipose tissue expansion, and survival was not significantly altered relative to low-fat-fed mice. Our findings support the notion that reduced survival in response to high-fat/high-sucrose feeding is linked to obesity development. Digital gene expression analyses, further validated by qPCR, demonstrated that the protein/sucrose ratio modulated global gene expression over time in liver and adipose tissue, affecting pathways related to metabolism and inflammation. Analysis of fecal bacterial DNA using the Mouse Intestinal Tract Chip revealed significant changes in the composition of the gut microbiota in relation to host age and dietary fat content, but not the protein/sucrose ratio. Accordingly, dietary fat rather than the protein/sucrose ratio or adiposity is a major driver shaping the gut microbiota, whereas the effect of a high-fat diet on survival is dependent on the protein/sucrose ratio.

KEYWORDS:

gut microbiota; high-fat diet; high-protein diet; obesity; survival

PMID:
27026084
DOI:
10.1152/ajpendo.00363.2015
[Indexed for MEDLINE]
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