Elsevier

Nutrition

Volume 21, Issue 10, October 2005, Pages 1052-1058
Nutrition

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

https://doi.org/10.1016/j.nut.2005.01.010Get rights and content

Abstract

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.

Introduction

It is well established that physical exercise increases overall energy expenditure in the body [1], [2], [3]. One of the most important metabolic effects of exercise is the enhanced uptake of blood glucose by skeletal muscles [4], a change that continues for a number of hours after cessation of exercise [5]. This enhanced uptake would be expected to decrease the amount of glucose available for hepatic lipogenesis.

There is evidence that exercise training may also downregulate hepatic lipogenic enzymes, thereby decreasing the availability of long-chain fatty acids required for the synthesis of triacylglycerol [6], [7], [8], [9]. In contrast to the liver, Ikeda et al. [10] recently reported that exercise training upregulates expression of lipogenic genes in mouse skeletal muscle. Skeletal muscle also contains triacylglycerol, another energy-rich substrate that may be used during prolonged exercise. Similar to glycogen supercompensation, skeletal muscle from trained human subjects has 2.0 to 2.5 times higher lipid content than muscle from untrained subjects [11]. Although it is established that exercise training causes various changes in lipogenic enzyme activity in the liver, very little is known regarding lipogenic enzymes in muscle.

Hepatic lipogenic enzymes are regulated by dietary and hormonal factors [9], [12], [13], [14], [15], [16], [17]. Lipogenic enzyme gene expression in rat liver is increased by a fat-free, high-carbohydrate diet but is decreased by a diet rich in polyunsaturated fats [18]. It has been shown that an excess intake of carbohydrate, particularly monosaccharides such as glucose and fructose, induces lipogenesis [19], [20]. Diet-induced lipogenesis is caused primarily by induction of hepatic lipogenic enzymes [9], [12], [14], with the primary mechanism for fatty acid synthase induction being transcriptional activation. However, little is known concerning dietary components, such as carbohydrates, proteins, or specific amino acids, that affect the activity of skeletal muscle lipogenic enzymes.

There is evidence that the type of dietary protein may affect liver lipogenic enzyme activities. For example, soy protein decreases hepatic triacylglycerol level compared with casein [21], [22] and was shown by Iritani et al. [21] to decrease the activity of hepatic lipogenic enzymes in rat liver. This effect was attributed to differences in the amino acid composition between casein and soy protein. Whey protein is also used mainly as the source of protein in dietary supplements. Accordingly, this study compared the effects of casein and whey protein as the source of dietary protein on lipogenic enzyme activities and mRNA expression in the liver and skeletal muscle of exercise-trained rats.

Section snippets

Animals

Male Sprague-Dawley rats (CLEA Japan, Inc., Tokyo, Japan) were used in this study. All rats were housed individually in temperature-controlled rooms (22°C), with light from 8:00 am to 8:00 pm and dark from 8:00 pm to 8:00 am. The study was approved by the animal committee of Meiji Seika Kaisha Ltd., Health and Bioscience Laboratories, with the animals receiving care under guidelines laid down by this committee.

Diets

The design of the experimental diets followed the AIN-93 protocol [23], and the

Initial body weight, food intake, and body weight gain

Table 2 presents changes in food intake and body weight gain. Food intake and body weight gain were similar with the casein and whey protein diets. However, we found that exercise training for 2 wk significantly decreased the gain in body weight.

Serum parameters

The two diets had no effect on serum triacylglycerol, glucose, insulin, or glucagon level. A significant decrease in serum glucose and insulin levels was observed in the exercise-trained groups compared with the sedentary groups (Table 3).

Liver enzyme activities

Compared with

Discussion

This is the first study to demonstrate that whey protein decreases the activity of liver lipogenic enzymes and mRNA expression of these enzymes, except for fatty acid synthase, compared with casein. In contrast, whey protein caused significant increases in skeletal muscle fatty acid synthase activity and mRNA expression compared with casein. Thus, induction of lipogenic enzymes resulting from a diet supplemented with whey protein is different between liver and skeletal muscle.

The effect of

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