Effect of Exercise on Hepatic Gene Expression in an Obese Mouse Model Using cDNA Microarrays

Abstract

To understand the molecular mechanisms involved in the effect of exercise training, we examined hepatic transcriptional profiles using cDNA microarrays in exercise-trained and untrained mice with diet-induced obesity. C57BL/6J male mice (n ϭ 10/group) were fed with a normal diet, high-fat diet (HFD), or HFD with exercise training for 12 weeks. The expression level of ϳ10,000 transcripts in liver tissues from each group was assessed using cDNA microarray analysis. Exercise training improved lipid profiles and hepatic steatosis and decreased body fat mass induced by the HFD. Seventy-three genes were differentially expressed in the HFD-and/or HFD with exercise training-treated groups, compared with the normal diet-and HFD-fed groups, respectively. Interestingly, the expression profiles involved in metabolism, such as elongation of very long chain fatty acids-like 2, lipin, and malic enzyme, were changed by exercise training. In addition, expression of genes altered by exercise training related to defense and stress response, including metallothionein 1 and 2 and heat shock protein, showed interesting findings. Our study showed beneficial effects of exercise training in preventing the development of obesity and metabolic disorders in mice with diet-induced obesity. Key words: cDNA microarray, C57BL/6J mouse, exercise training, high-fat diet, metabolismConsumption of high-fat diets (HFDs) 1 for extended periods can lead to the development of obesity and diabetes (1), adversely affecting the health of humans and experimental animals (1,2). To elucidate the effects of exercise on obesity induced by HFD, we studied liver tissues in C57BL/6J mice because the liver plays an integral part in the physiology of exercise. This organ supplies energy substrates to peripheral tissues by the Cori cycle and glycogen catabolism and is important for detoxification.Exercise training is known to improve the metabolic profile, including reduced hepatic accumulation of total fat and cholesterol in rats fed an HFD (3). Furthermore, exercise regulates the gene expression related to metabolism, defense, and stress responses (3-5). However, the results in most cases have been obtained in a gene-by-gene manner. For this reason, we chose the microarray approach as a global analysis of the genetic basis for the relationship between exercise and obesity. Therefore, we used cDNA microarray, containing ϳ10,000 mouse transcripts. Some of them were already known to be sensitive to exercise in an obesity model. However, others have been newly identified. We describe important new effects of exercise on the expression of genes related to energy metabolism, defense, and stress responses.

Hepatic Glucagon Action Is Essential for Exercise-Induced Reversal of Mouse Fatty Liver

“…Forced exercise can define work but is associated with less volume and may be more stressful. Nonetheless, both paradigms improve insulin sensitivity, reduce hepatic fat, and alter liver gene expression (6,9–12). Our group has also shown that acute exercise increases plasma glucagon (20,23).…”

Association of a Polymorphism in the Lipin 1 Gene With Systolic Blood Pressure in Men

“…Interestingly, physical activity, which reduces intra-abdominal adiposity effectively, increases the expression of LPIN1. 30 In conclusion, our study demonstrated a significant association between rs10495584 and systolic blood pressure in men. Although this SNP is in high LD with rs11524, in which the major allele forms an exonic splicing silencer sequence, it remains to be established how these two SNPs affect blood pressure by alternative splicing.…”

Activation of the mitogen-activated protein kinase (MAPK) signalling pathway in the liver of mice is related to plasma glucose levels after acute exercise

“…Compared with the numerous reports on the transcriptional regulation of genes in the working muscle, remarkably little data on exercise-induced gene expression in the liver are available. Some studies have investigated the effects of long-term exercise training on hepatic expression of metabolic enzymes in obese or diabetic rodents [21][22][23]. The expression of genes involved in the regulation of glucose and fatty acid metabolism was also found to be regulated by one single bout of exercise.…”