Infrequent Feeding of Restricted Amounts of Food Induces Stress and Adipose Tissue Inflammation, Contributing to Impaired Glucose Metabolism

Abstract

Food restriction has been recommended as an effective strategy for body weight loss. However, food restriction can alter biological rhythms and leads to physiological stress. However, relatively little is known about the physiological impact of different methods of food restriction. Therefore, we investigated whether different schedules of restricted food intake induce physiological stress and then contribute to glucose metabolism disorder. C57BL/6 mice were fed a high fat diet (60% fat) for 8 weeks and then randomly divided into three groups: the control group was continuously fed the high fat diet; the two food restriction groups were fed 50% of food consumed by the control mice with one group (FR1) being fed the full amount once a day and the other group (FR2) being fed the same total amount as FR1 twice a day for 3 days. We found increased body weight loss, the serum triglyceride levels, the expression of lipolysis-related genes, and serum corticosterone levels in the FR1 group compared with the FR2 group. The immune cell population infiltrating the adipose tissue and the expression of monocyte chemoattractant protein (MCP-1) and toll-like receptor (TLR-4) mRNA were increased in the FR1 group compared with the control. To determine whether long-term dietary manipulation is associated with metabolic disorders, mice were fed a restricted diet for 3 days alternating with an unrestricted diet for the following 4 days and this was repeated for 8 weeks. The alternating FR1 group showed impaired glucose tolerance compared with the alternating FR2 group. These results indicate that infrequent feeding of restricted amounts of food could induce stress hormones, lipolysis, adipose tissue immune cell infiltration and inflammation, which in turn may promote glucose metabolism disorder.