Effect of a long-term high-protein diet on survival, obesity development and gut microbiota in mice
Kiilerich, Pia; Myrmel, Lene Secher; Fjære, Even; Hao, Qin; Hugenholz, Floor; Sonne, Si Brask; Derrien, Muriel; Pedersen, Lone Møller; Petersen, Rasmus Koefoed; Mortensen, Alicja; Licht, Tine Rask; Rømer, Maria Unni; Vogel, Ulla Birgitte; Waagbø, Linn Jeanette; Giallourou, Natasa; Feng, Qiang; Xiao, Liang; Liu, Chuan; Liaset, Bjørn; Kleerebezem, Michiel; Wang, Jun; Madsen, Lise; Kristiansen, Karsten
Abstract
Female C57BL/6J mice were fed a regular low fat diet or high fat diets combined with either
high or low protein: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 life-long
weight gain, 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 modulating 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.
American Journal of Physiology - Endocrinology and Metabolism — 2016, DOI:10.1152/ajpendo.00363.2015