title: Effect of a long-term high-protein diet on survival, obesity development, and gut microbiota in mice.
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.
authors.affiliation: Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, Copenhagen, Denmark;
authors.forename: Pia
authors.identifier: http://orcid.org/0000-0001-5665-6074
authors.initials: P
authors.lastname: Kiilerich
authors.affiliation: Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, Copenhagen, Denmark; National Institute of Nutrition and Seafood Research, Bergen, Norway;
authors.forename: Lene Secher
authors.initials: LS
authors.lastname: Myrmel
authors.affiliation: Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, Copenhagen, Denmark; National Institute of Nutrition and Seafood Research, Bergen, Norway;
authors.forename: Even
authors.initials: E
authors.lastname: Fjære
authors.affiliation: Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, Copenhagen, Denmark;
authors.forename: Qin
authors.initials: Q
authors.lastname: Hao
authors.affiliation: Top Institute Food and Nutrition, Wageningen, The Netherlands;
authors.forename: Floor
authors.initials: F
authors.lastname: Hugenholtz
authors.affiliation: Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, Copenhagen, Denmark;
authors.forename: Si Brask
authors.initials: SB
authors.lastname: Sonne
authors.affiliation: Top Institute Food and Nutrition, Wageningen, The Netherlands;
authors.forename: Muriel
authors.initials: M
authors.lastname: Derrien
authors.affiliation: Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, Copenhagen, Denmark;
authors.forename: Lone Møller
authors.initials: LM
authors.lastname: Pedersen
authors.affiliation: Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, Copenhagen, Denmark;
authors.forename: Rasmus Koefoed
authors.initials: RK
authors.lastname: Petersen
authors.affiliation: National Food Institute, Technical University of Denmark, Søborg, Denmark;
authors.forename: Alicja
authors.initials: A
authors.lastname: Mortensen
authors.affiliation: National Food Institute, Technical University of Denmark, Søborg, Denmark;
authors.forename: Tine Rask
authors.initials: TR
authors.lastname: Licht
authors.affiliation: Department of Veterinary Disease Biology, University of Copenhagen, Copenhagen, Denmark; Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, University of Copenhagen, Denmark;
authors.forename: Maria Unni
authors.initials: MU
authors.lastname: Rømer
authors.affiliation: National Research Centre for the Working Environment, Copenhagen, Denmark;
authors.forename: Ulla Birgitte
authors.initials: UB
authors.lastname: Vogel
authors.affiliation: National Institute of Nutrition and Seafood Research, Bergen, Norway;
authors.forename: Linn Jeanette
authors.initials: LJ
authors.lastname: Waagbø
authors.affiliation: Top Institute Food and Nutrition, Wageningen, The Netherlands;
authors.forename: Natasa
authors.initials: N
authors.lastname: Giallourou
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Feng
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Xiao
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Liu
authors.affiliation: National Institute of Nutrition and Seafood Research, Bergen, Norway;
authors.forename: Bjørn
authors.initials: B
authors.lastname: Liaset
authors.affiliation: Top Institute Food and Nutrition, Wageningen, The Netherlands; Host Microbe Interactomics Group, Wageningen University, Wageningen, The Netherlands;
authors.forename: Michiel
authors.initials: M
authors.lastname: Kleerebezem
authors.affiliation: 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.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Lise
authors.identifier: http://orcid.org/0000-0003-4468-1947
authors.initials: L
authors.lastname: Madsen
authors.affiliation: Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, Copenhagen, Denmark; BGI-Shenzhen, Shenzhen, China, kk@bio.ku.dk.
authors.forename: Karsten
authors.initials: K
authors.lastname: Kristiansen
mesh_terms: D000818:Animals; D018752:Diet, Fat-Restricted; D004044:Dietary Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D019422:Dietary Sucrose / Q000009:adverse effects / Q000493:pharmacokinetics*; D005260:Female; D000069196:Gastrointestinal Microbiome / Q000502:physiology*; D008137:Longitudinal Studies; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000209:etiology / Q000378:metabolism*; D015996:Survival Rate
chemical_list: D004044:Dietary Proteins; D019422:Dietary Sucrose
keywords: gut microbiota; high-fat diet; high-protein diet; obesity; survival