Increased energy expenditure and insulin sensitivity, but not protection from obesity, in phosphatidylethanolamine methyltransferase knockout mice on long‐term high‐fat diet feeding

Abstract

Increased energy expenditure can prevent diet induced obesity. Mice with a whole body knockout for phosphatidylethanolamine methyltransferase (PEMTKO) are protected from obesity induced by a short-term high-fat diet (HFD) feeding due to increased energy expenditure. However, the effects of long-term HFD feeding on body weight, energy expenditure and insulin sensitivity in these mice are unknown. We hypothesized that long-term HFD feeding will yield wildtype (WT) and PEMTKO mice that would be equally obese. WT and PEMTKO mice were placed on a 6-months HFD. Body weight, body composition, metabolic rate, food intake and spontaneous movement were measured periodically. Before mice were placed on HFD, WT and PEMTKO did not differ in any of these parameters. At 10th wk of HFD, PEMTKO mice had reduced body weight, body composition and increased energy expenditure without a decrease in food intake or an increase in activity compared to WT controls. At 20th wk of HFD, body weights between WT and PEMTKO were no longer different. After the 6-month HFD feeding, metabolic rate and glucose tolerance remained elevated in PEMTKO mice, suggesting increased energy expenditure alone promoted an increase in insulin sensitivity. In summary, elevated energy expenditure in PEMTKO mice delays weight gain induced by HFD feeding. PEMTKO mice are not protected from diet-induced obesity by long-term HFD feeding, but they remain exquisitely insulin sensitive probably due to their sustained increase in metabolic rate. Pharmacological inactivation of PEMT may be useful not only for preventing obesity, but also for promoting insulin sensitivity in the treatment of metabolic disorders.