Basic nutritional investigationDietary whey protein downregulates fatty acid synthesis in the liver, but upregulates it in skeletal muscle of exercise-trained rats
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
References (40)
- et al.
Detailed body composition analysis on female rats subjected to a program of swimming
J Nutr
(1973) - et al.
Exercise down-regulates hepatic lipogenic enzymes in food-deprived and refed rats
J Nutr
(1996) - et al.
Up-regulation of SREBP-1c and lipogenic genes in skeletal muscles after exercise training
Biochem Biophys Res Commun
(2002) - et al.
Regulation of hepatic lipogenic enzyme gene expression by diet quantity in rats fed a fat-free, high carbohydrate diet
J Nutr
(1992) - et al.
Hormonal regulation of mouse fatty acid synthase gene transcription in liver
J Biol Chem
(1989) - et al.
Suppression of fatty acid synthase promoter by polyunsaturated fatty acids
J Lipid Res
(2002) - et al.
Inhibition of fatty acid synthesis decreases very low density lipoprotein secretion in the hamster
J Lipid Res
(1992) - et al.
Effects of dietary proteins on lipogenic enzymes in rat liver
J Nutr
(1986) - et al.
Dietary orotic acid affects antioxidant enzyme mRNA levels and oxidative damage to lipids and proteins in rat liver
J Nutr Biochem
(2002) - et al.
AIN-93 purified diets for laboratory rodentsfinal report of the American Institute of Nutrition ad hoc writing committee on the reformulation of the AIN-76A rodent diet
J Nutr
(1993)
Mutarotase effect on colorimetric determination of blood glucose with -D-glucose oxidase
Clin Chim Acta
Citrate synthase
Methods Enzymol
ATP citrate lyase (citrate cleavage enzyme)
Methods Enzymol
Malic enzyme
Methods Enzymol
Glucose-6-phosphate dehydrogenase from human erythrocytes
Methods Enzymol
Acetyl-CoA carboxylase from rat liver
Methods Enzymol
Fatty-acid synthase from rat liver
Methods Enzymol
Measurement of protein using bicinchoninic acid
Anal Biochem
Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction
Anal Biochem
Mitochondrial citric acid cycle and related enzymesadaptive response to exercise
Biochem Biophys Res Commun
Cited by (43)
Consumption of a whey protein-enriched diet may prevent hepatic steatosis associated with weight gain in elderly women
2015, Nutrition, Metabolism and Cardiovascular DiseasesCitation Excerpt :Emerging evidence from short-term intervention studies in humans suggests that consumption of protein sourced from whey, a milk protein [11,12], may induce weight loss, improve insulin sensitivity and lower plasma lipids [13,14]. In addition, studies in animal models of FLD report that whey protein consumption may improve liver biochemistry and histology [15–17]. Notably, a recent rodent study reported that when all macronutrients except for protein quality (whey versus casein) were matched, whey protein consumption reduced liver triglyceride content and inhibited expression of genes that regulate fatty acid metabolism [18].
A dipeptide and an amino acid present in whey protein hydrolysate increase translocation of GLUT-4 to the plasma membrane in Wistar rats
2013, Food ChemistryCitation Excerpt :Whey protein (WP) represents almost 20% of the total protein in bovine milk and has been recognised for its high nutritional quality, fast absorption and as a rich source of branched-chain amino acids (BCAAs) (Hulmi, Lockwood, & Stout, 2010). Some properties associated with the whey proteins, especially in their hydrolysed form, have been the subject of some investigations; properties such as the improved physical resistance of rats subjected to physical exhaustion (Pimenta, Abecia-Soria, Auler, & Amaya-Farfan, 2006), a reduction in muscle injury enzyme indicators (LDH, CK) in soccer players during competition (Lollo, Amaya-Farfan, & Carvalho-Silva, 2011), contribution to protection against stress (de Moura, Lollo, Morato, Carneiro, & Amaya-Farfan, 2013), an increase in muscle fatty acids for use as an energy source during exercise (Morifuji, Sakai, Sanbongi, & Sugiura, 2005a) and the capacity to recover the glycogen levels in the liver and skeletal muscle after exercise (Faria, Nery-Diez, Lollo, Amaya-Farfan, & Ferreira, 2012; Morifuji, Kanda, Koga, Kawanaka, & Higuchi, 2010; Morifuji, Sakai, Sanbongi, & Sugiura, 2005b; Pimenta et al., 2006). Muscle glycogen synthesis is limited by the availability of glucose, and in skeletal muscle glucose transport occurs mainly via the glucose transport carrier proteins (GLUTs).