DIO2 and obesity due to melanocortin 4 receptor deficiency: Considering the role of the bile acid-TGR5-Dio2 signaling in thermogenesis [23], an energy-dissipating process, we further hypothesized that altered bile acid homeostasis may protect L1-KO mice from HFD-induced obesity by increasing energy expenditure through the TGR5-Dio2 pathway.