Cold exposure promotes obesity and impairs glucose homeostasis in mice subjected to a high-fat diet

Cold exposure is considered to be a form of stress and has various adverse effects on the body. The present study aimed to investigate the effects of chronic daily cold exposure on food intake, body weight, serum glucose levels and the central energy balance regulatory pathway in mice fed with a high-fat diet (HFD). C57BL/6 mice were divided into two groups, which were fed with a standard chow or with a HFD. Half of the mice in each group were exposed to ice-cold water for 1 h/day for 7 weeks, while the controls were exposed to room temperature. Chronic daily cold exposure significantly increased energy intake, body weight and serum glucose levels in HFD-fed mice compared with the control group. In addition, 1 h after the final cold exposure, c-fos immunoreactivity was significantly increased in the central amygdala of HFD-fed mice compared with HFD-fed mice without cold exposure, indicating neuronal activation in this brain region. Notably, 61% of these c-fos neurons co-expressed the neuropeptide Y (NPY), and the orexigenic peptide levels were significantly increased in the central amygdala of cold-exposed mice compared with control mice. Notably, cold exposure significantly decreased the anorexigenic brain-derived neurotropic factor (BDNF) messenger RNA (mRNA) levels in the ventromedial hypothalamic nucleus and increased growth hormone releasing hormone (GHRH) mRNA in the paraventricular nucleus. NPY-ergic neurons in the central amygdala were activated by chronic cold exposure in mice on HFD via neuronal pathways to decrease BDNF and increase GHRH mRNA expression, possibly contributing to the development of obesity and impairment of glucose homeostasis.