Health concerns around obesity have driven the search for novel approaches to therapy including lifestyle changes and supplementation of diet. Previous work showed improvements in lipid metabolism in obese mice supplemented with betaine, and in healthy people, betaine has been used to enhance the benefits of exercise. Here we explored the potential synergy between betaine and exercise as an intervention for high-fat diet (HFD)-induced obesity. We hypothesized that combining treadmill exercise and orally administered betaine would provide synergistic benefits for ameliorating diet-induced obesity.
Male C57BL/6J mice were fed either chow (Con) or HFD to induce obesity then HFD mice were separated into these groups: HFD, HFD with betaine (HB), HFD with exercise (HEx), and HFD with betaine and exercise (HBEx); treadmill exercise (15 m/min for 45 min, 6 days/week) and/or 1.5% (w/v) betaine in drinking water. Body composition and intraperitoneal glucose tolerance tests (GTT) were assessed prior to and after treatment (5 weeks).
Administration of betaine alone did not affect glucose tolerance or insulin secretion during GTT. Exercise lowered body weight and fat composition, with or without betaine. Whilst HEx mice exhibited mildly improved glucose tolerance during GTT, HBEx mice had significantly reduced blood glucose levels compared to HFD mice, as well as reduced insulin levels, which were comparable to Con. Interestingly, all HFD-groups showed upregulation of hepatic Pparg despite reduced hepatic triglycerides in mice undergoing exercise. Moreover, HFD-induced increases in Mpc1 and Pc were normalized in mice receiving combined exercise and betaine treatment, suggesting the possibility that the improvements observed during GTT may be linked to changes in glucose metabolism. Thus, 1.5% (w/v) betaine in drinking water augmented the beneficial effects of exercise on metabolic health in obese mice, which may be facilitated by processes involved in glucose metabolism with limited effects on hepatic lipid metabolism.