Impaired adaptation of energy intake induces severe obesity in aged mice on a high-fat diet.

High-fat diet (HFD) feeding induces inflammation in various tissues, including the nodose ganglion and hypothalamus, resulting in obesity and metabolic disorders. In this study, we investigated the effect of short-term HFD on aged and young mice. Aged mice easily gained weight during short-term HFD feeding, and required many days to adapt their energy intake. One-day HFD in aged mice induced inflammation in the distal colon, but not in the nodose ganglion or hypothalamus. The anorexic effect of glucagon-like peptide-1 (GLP-1) was attenuated in aged mice. Intraperitoneal administration of GLP-1 did not induce expression of genes that regulate feeding in the hypothalamus of aged mice. mRNA expression of the gene encoding the GLP-1 receptor (Glp1r) in the nodose ganglion was significantly lower in aged mice than in young mice. Our findings suggest that adaptation of energy intake regulation was attenuated in aged mice, causing them to become obese in response to short-term HFD feeding.