Whey protein effects on energy balance link the intestinal mechanisms of energy absorption with adiposity and hypothalamic neuropeptide gene expression

Kanishka N Nilaweera, Raul Cabrera-Rubio, John R Speakman, Paula M O' Connor, AnneMarie McAuliffe, Caitriona M Guinane, Elaine Lawton, Fiona Crispie, Mònica Aguilera, Maurice Stanley, Serena Boscaini, Susan Joyce, Silvia Melgar, John F Cryan, Paul D Cotter

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)


We tested the hypothesis that dietary whey protein isolate (WPI) affects the intestinal mechanisms related to energy absorption and that the resulting energy deficit is compensated by changes in energy balance to support growth. C57BL/6 mice were provided a diet enriched with WPI with varied sucrose content, and the impact on energy balance-related parameters was investigated. As part of a high-sucrose diet, WPI reduced the hypothalamic expression of pro-opiomelanocortin gene expression and increased energy intake. The energy expenditure was unaffected, but epididymal weight was reduced, indicating an energy loss. Notably, there was a reduction in the ileum gene expression for amino acid transporter SLC6a19, glucose transporter 2, and fatty acid transporter 4. The composition of the gut microbiota also changed, where Firmicutes were reduced. The above changes indicated reduced energy absorption through the intestine. We propose that this mobilized energy in the adipose tissue and caused hypothalamic changes that increased energy intake, acting to counteract the energy deficit arising in the intestine. Lowering the sucrose content in the WPI diet increased energy expenditure. This further reduced epididymal weight and plasma leptin, whereupon hypothalamic ghrelin gene expression and the intestinal weight were both increased. These data suggest that when the intestine-adipose-hypothalamic pathway is subjected to an additional energy loss (now in the adipose tissue), compensatory changes attempt to assimilate more energy. Notably, WPI and sucrose content interact to enable the component mechanisms of this pathway.
Original languageEnglish
Pages (from-to)E1-E11
Number of pages11
JournalAmerican Journal of Physiology: Endocrinology and Metabolism
Issue number1
Early online date21 Mar 2017
Publication statusPublished - 1 Jul 2017

Bibliographical note

We wish to thank Dr. Fiona Crispie for assistance with the sequencing of DNA samples, Ms Donjete Statovci for RNA analysis, Dr. Jim Grant for carrying out statistical analyses, and Ms. Martina O’Brian for measuring crude protein content in the faeces. This work was supported by Teagasc, Ireland and in part by a research grant from Science Foundation Ireland (SFI) under the Grant Number SFI/16/BBSRC/3389 and the BBSRC under the Grant Reference BB/P009875/1 (KNN and JRS) and by SFI Grant Number SFI/12/RC/2273 (JFC and APC Microbiome Institute).


  • Journal Article
  • whey proteins
  • energy balance
  • intestine
  • gut microbiota
  • gene expression


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