Whey protein reduces early life weight gain in mice fed a high-fat diet

PLoS One. 2013 Aug 6;8(8):e71439. doi: 10.1371/journal.pone.0071439. Print 2013.


An increasing number of studies indicate that dairy products, including whey protein, alleviate several disorders of the metabolic syndrome. Here, we investigated the effects of whey protein isolate (whey) in mice fed a high-fat diet hypothesising that the metabolic effects of whey would be associated with changes in the gut microbiota composition. Five-week-old male C57BL/6 mice were fed a high-fat diet ad libitum for 14 weeks with the protein source being either whey or casein. Faeces were collected at week 0, 7, and 13 and the fecal microbiota was analysed by denaturing gradient gel electrophoresis analyses of PCR-derived 16S rRNA gene (V3-region) amplicons. At the end of the study, plasma samples were collected and assayed for glucose, insulin and lipids. Whey significantly reduced body weight gain during the first four weeks of the study compared with casein (P<0.001-0.05). Hereafter weight gain was similar resulting in a 15% lower final body weight in the whey group relative to casein (34.0±1.0 g vs. 40.2±1.3 g, P<0.001). Food intake was unaffected by protein source throughout the study period. Fasting insulin was lower in the whey group (P<0.01) and glucose clearance was improved after an oral glucose challenge (P<0.05). Plasma cholesterol was lowered by whey compared to casein (P<0.001). The composition of the fecal microbiota differed between high- and low-fat groups at 13 weeks (P<0.05) whereas no difference was seen between whey and casein. In conclusion, whey initially reduced weight gain in young C57BL/6 mice fed a high-fat diet compared to casein. Although the effect on weight gain ceased, whey alleviated glucose intolerance, improved insulin sensitivity and reduced plasma cholesterol. These findings could not be explained by changes in food intake or gut microbiota composition. Further studies are needed to clarify the mechanisms behind the metabolic effects of whey.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Body Weight / drug effects
  • Diet, High-Fat* / adverse effects
  • Glucose Intolerance / prevention & control
  • Insulin Resistance
  • Lipids / blood
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Milk Proteins / pharmacology*
  • Organ Size / drug effects
  • Weight Gain / drug effects*
  • Whey Proteins


  • Lipids
  • Milk Proteins
  • Whey Proteins

Grants and funding

This work was supported by the Danish Agency for Science, Technology and Innovation (grant No. 2101-07-0094), www.fi.dk. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.