Protein quality and quantity influence the effect of dietary fat on weight gain and tissue partitioning via host-microbiota changes

Oleksandr Nychyk, Wiley Barton, Agata M. Rudolf, Serena Boscaini, Aaron Walsh, Thomaz F.S. Bastiaanssen, Linda Giblin, Paul Cormican, Liang Chen, Yolanda Piotrowicz, Davina Derous, Áine Fanning, Xiaofei Yin, Jim Grant, Silvia Melgar, Lorraine Brennan, Sharon E. Mitchell, John F. Cryan, Jun Wang, Paul D. CotterJohn R. Speakman, Kanishka N. Nilaweera

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)
11 Downloads (Pure)


We investigated how protein quantity (10%–30%) and quality (casein and whey) interact with dietary fat (20%–55%) to affect metabolic health in adult mice. Although dietary fat was the main driver of body weight gain and individual tissue weight, high (30%) casein intake accentuated and high whey intake reduced the negative metabolic aspects of high fat. Jejunum and liver transcriptomics revealed increased intestinal permeability, low-grade inflammation, altered lipid metabolism, and liver dysfunction in casein-fed but not whey-fed animals. These differential effects were accompanied by altered gut size and microbial functions related to amino acid degradation and lipid metabolism. Fecal microbiota transfer confirmed that the casein microbiota increases and the whey microbiota impedes weight gain. These data show that the effects of dietary fat on weight gain and tissue partitioning are further influenced by the quantity and quality of the associated protein, primarily via effects on the microbiota.
Original languageEnglish
Article number109093
Number of pages34
JournalCell Reports
Issue number6
Early online date11 May 2021
Publication statusPublished - 11 May 2021

Bibliographical note

This work was supported by a research grant from Science Foundation Ireland
(SFI) under grant SFI/16/BBSRC/3389, BBSRC under grant number BB/
P009875/1 (to K.N.N. and J.R.S.), and in part by SFI and the Department of
Agriculture, Food and Marine under grant 16/RC/3835 (to VistaMilk). We thank
Conall Strain, David Mannion, and John Leech for contributing to the metabolomics analysis. We thank Alina Kondrashina for help with the Milliplex


  • high fat intake
  • high protein intake
  • energy metabolism
  • gut microbiota
  • adiposity
  • whey protein
  • IGF1
  • inflammation
  • body weight and tissue correlation
  • gut permeability


Dive into the research topics of 'Protein quality and quantity influence the effect of dietary fat on weight gain and tissue partitioning via host-microbiota changes'. Together they form a unique fingerprint.

Cite this