Supplemental epilactose prevents metabolic disorders through uncoupling protein-1 induction in the skeletal muscle of mice fed high-fat diets

Abstract

Obesity is one of the major health problems throughout the world. The present study investigated the preventive effect of epilactose -a rare non-digestible disaccharide -on obesity and metabolic disorders in mice fed high-fat (HF) diets. Feeding with HF diets increased body weight gain, fat pad weight and adipocyte size in mice (P < 0·01), and these increases were effectively prevented by the use of supplemental epilactose without influencing food intake (P < 0·01). Caecal pools of SCFA such as acetic and propionic acids in mice fed epilactose were higher compared with mice not receiving epilactose. Supplemental epilactose increased the expression of uncoupling protein (UCP)-1, which enhances energy expenditure, to 2-fold in the gastrocnemius muscle (P = 0·04) and to 1·3-fold in the brown adipose tissue (P = 0·02) in mice fed HF diets. Feeding HF diets induced pro-inflammatory macrophage infiltration into white adipose tissue, as indicated by the increased expression of monocyte chemotactic protein-1, TNF-α and F4/80, and these increases were attenuated by supplemental epilactose. In differentiated myogenic-like C2C12 cells, propionic acid, but not acetic or n-butyric acids, directly enhanced UCP-1 expression by approximately 2-fold (P < 0·01). Taken together, these findings indicate that the epilactose-mediated increase in UCP-1 in the skeletal muscle and brown adipose tissue can enhance whole-body energy expenditure, leading to effective prevention of obesity and metabolic disorders in mice fed HF diets. It is suggested that propionic acid -a bacterial metabolite -acts as a mediator to induce UCP-1 expression in skeletal muscles.Key words: Epilactose: Propionic acid: Obesity: Uncoupling protein: Skeletal muscle Non-digestible carbohydrates such as dietary fibres and oligosaccharides have a variety of beneficial effects on our health. Epilactose (4-O-β-galactopyranosyl-D-mannose) is a rare nondigestible disaccharide, which can be produced in considerable amounts by heating and alkali treatment of cows' milk (1) . Recently, we have developed a method for the mass-production of epilactose using cellobiose 2-epimerase (EC 5.1.3.11) from the ruminal strain Ruminococcus albus NE1 (2) . Although our previous studies have found that epilactose enhances the absorption of intestinal Ca and Fe in rodents (3) , information on its biological functions remains quite limited. As previous studies have demonstrated that some non-digestible carbohydrates ameliorate metabolic disorders such as obesity, epilactose also may have a potential to prevent these disorders.Obesity and related diseases, such as diabetes and CVD, have emerged as major health problems in many countries, particularly in the West (4) . It is known that obesity and diabetes are the results of a complex interaction between genetic and environmental factors. In particular, the intake of a fat-enriched diet and intake of excessive calories are primary factors associated with the increased occurrence and further progression of metabolic disorders. At the ...

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