The role of FGF21 in regulating energy homeostasis

Fibroblast Growth Factor 21 (FGF21) is a hormone that is produced from the liver which has pleiotropic effects. Physiologically, FGF21 increases energy expenditure, increases glucose uptake, enhances glucose tolerance, and increases peripheral insulin sensitivity. Pharmacologically, FGF21 reverses obesity and diabetes in animal models and significantly improves metabolic profiles in humans through unknown mechanisms. We hypothesized that the physiological actions of FGF21 may provide insights to explain FGF21’s beneficial pharmacological effects. The overall theme of this work was to identify the elusive mechanism by which FGF21 regulates energy homeostasis. In chapter 1, I review some adipokines and hepatokines that regulate energy homeostasis. In chapter 2, I provide background on fibroblast growth factors (FGFs), metabolic FGFs, and the tissue-specific effects of FGF21. In chapter 3, I will review the role of growth factors in thermoregulation. In chapter 4, we use tissue-specific loss of function models to investigate the trajectory of FGF21’s thermogenic effects during prolonged cold. In chapter 5, we specifically address the necessity and sufficiency of FGF21 signaling directly to adipose tissue, and the contribution of the adipokine adiponectin in mediating FGF21’s metabolic effects. In chapter 6, I summarize our results, reflect upon the ramifications of these results, and briefly address potential future experiments given our results on the physiological and pharmacological actions of FGF21 in adipose tissues.