Effect of aging and obesity on GLUT12 expression in small intestine, adipose tissue, muscle and kidney, and its regulation by docosahexaenoic acid and exercise in mice.

Obesity is characterized by excessive fat accumulation and inflammation. Aging has also been characterized as an inflammatory condition, frequently accompanied by accumulation of visceral fat. Beneficial effects of exercise and n-3 long-chain polyunsaturated fatty acids in metabolic disorders have been described. GLUT12 is one of the less investigated members of the GLUT family. Glucose, insulin and TNF-α induce GLUT12 translocation to the membrane in muscle, adipose tissue and intestine. We aimed to investigate GLUT12 expression in obesity and aging, and under diet supplementation with docosahexaenoic acid (DHA) alone or in combination with physical exercise in mice. Aging increased GLUT12 expression in intestine, kidney and adipose tissue, whereas obesity reduced it. No changes on the transporter occurred in skeletal muscle. In obese 18-months-old mice, DHA further decreased GLUT12 in the four organs. Aerobic exercise alone did not modify GLUT12, but the changes triggered by exercise were able to prevent DHA diminishing effect, and almost restored GLUT12 basal levels. In conclusion, the downregulation of metabolism in aging would be a stimulus to upregulate GLUT12 expression. Contrary, obesity, an excessive energy condition, would induce GLUT12 downregulation. The combination of exercise and DHA would contribute to restore basal function of GLUT12. Novelty bullets: • In small intestine, kidney and adipose tissue aging increase GLUT12 protein expression whereas obesity reduces it. • Dietary DHA decreases GLUT12 in small intestine, kidney, adipose tissue and skeletal muscle. • Exercise alone does not modify GLUT12 expression, nevertheless exercise prevents the DHA-diminishing effect on GLUT12.