Figure 10.
Primary phenotype and the underlying mechanisms involved and secondary phenotype in BATIGFIRDKO mice. Lack of IGFIR/IR caused severe brown fat atrophy and mitochondrial damage related to cristae disruption and also the loss of essential components of the protein machinery involved in the mitochondrial quality control, such as PINK-1, and mitochondrial dynamics, such as MFN-2 and OPA-1. More important, DKO showed impaired brown fat thermogenesis upon cold exposure based on a failure in the mitochondrial fission mechanisms and a much lower UCP1 content. However, DKO mice increased the number of beige cell clusters observed within the inguinal fat. As a result, DKO mice showed obesity susceptibility, as revealed by increased body fat mass and insulin resistance. Upon consumption of an HFD, DKO vs control mice showed manifest obesity, revealed by increased body weight, increased adiposity, insulin resistance, hyperinsulinemia, and hypertriglyceridemia, mobilizing lipids to peripheral tissues as the liver. CNS, central nervous system; SNS, sympathetic nervous system; TG, triglycerides; β3AR, β-3 adrenergic receptor.