Dietary whey protein downregulates fatty acid synthesis in the liver, but upregulates it in skeletal muscle of exercise-trained rats

Nutrition. 2005 Oct;21(10):1052-8. doi: 10.1016/j.nut.2005.01.010.


Objective: This study compared the effects of casein and whey protein as the source of dietary protein on the activity of lipogenic enzymes and mRNA levels in the liver and skeletal muscle of exercise-trained rats.

Methods: Twenty-eight male Sprague-Dawley rats were randomly assigned to one of four groups (n = 7/group). Rats were assigned to sedentary or exercise-trained groups and were fed the casein or whey protein diet. Rats in the exercise groups were trained for 2 wk using a swimming exercise for 120 min/d and 6 d/wk.

Results: A significant decrease in the activity of the hepatic lipogenic enzymes, glucose-6-phosphate dehydrogenase, malic enzyme, adenosine triphosphate citrate lyase, acetyl-coenzyme A carboxylase, and fatty acid synthase (FASN) was observed in rats fed whey protein compared with animals fed casein. Compared with the casein diet, the whey protein diet also lowered mRNA expression of these enzymes, except for FASN. In contrast to the findings in liver, whey protein, as compared with casein, increased skeletal muscle FASN activity and mRNA. Further, exercise training resulted in increased skeletal muscle glucose-6-phosphate dehydrogenase and FASN activity and adenosine triphosphate citrate lyase, acetyl-coenzyme A carboxylase-1, and FASN mRNA expression.

Conclusions: Exercise training or whey protein may play an important role in suppressing hepatic fatty acid synthesis, thereby decreasing accumulation of body fat and stimulating the skeletal muscle to increase energy substrate as fat during prolonged exercise.

MeSH terms

  • Analysis of Variance
  • Animals
  • Caseins / administration & dosage
  • Caseins / pharmacology
  • Down-Regulation / drug effects
  • Fatty Acids / biosynthesis*
  • Gene Expression Regulation, Enzymologic
  • Liver / drug effects
  • Liver / enzymology
  • Liver / metabolism*
  • Male
  • Milk Proteins / administration & dosage
  • Milk Proteins / pharmacology*
  • Muscle, Skeletal / enzymology
  • Muscle, Skeletal / metabolism*
  • Physical Conditioning, Animal / physiology*
  • RNA, Messenger / metabolism
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Up-Regulation / drug effects
  • Whey Proteins


  • Caseins
  • Fatty Acids
  • Milk Proteins
  • RNA, Messenger
  • Whey Proteins