An enriched environment re-establishes metabolic homeostasis by reducing obesity-induced inflammation

Obesity can lead to chronic inflammation in different tissues including the adipose tissue, liver, pancreas, and brain. This inflammatory process generates insulin and leptin resistance, as well as alterations in glucose and lipid metabolism, leading to the development of degenerative diseases including type II diabetes. Additionally, the inhibition of inflammatory signaling can prevent the development of obesity and restore insulin sensitivity. Different studies have shown that an enriched environment (EE) has beneficial effects on learning and memory via enhancing central nervous system activity. Housing in an EE also regulates the differentiation and activation of immune cells and reduces inflammation in different disease models. Therefore, in the current study we explore whether an EE is capable of restoring energy balance in obese mice that previously presented metabolic alterations. We discovered that an EE improved glucose metabolism, increased insulin signaling in the liver, and reduced hepatic steatosis in mice fed with high-fat diet (HFD). Furthermore, the EE reduced the number of infiltrating macrophages and the levels of inflammatory cytokines in the white adipose tissue (WAT), and increased the production of anti-inflammatory cytokines, lipolysis, and browning in the WAT of HFD-fed mice. Finally, we found reduced inflammatory signaling and increased anorexigenic signaling in the hypothalamus of HFD-fed mice exposed to an EE. These data indicate that an EE is able to restore the metabolic imbalance caused from HFD feeding. Thus, we propose EE as a novel therapeutic approach to treat obesity-related metabolic alterations.