Figure 4. Genetically-induced Insulin deficiency enhances energy expenditure and adipose browning, while preventing adipose expansion, glucose intolerance and hepatosteatosis in mice on a high fat diet.
The Figure compares the effects of HFD on genetic mouse models that display either a normal hyperinsulinemic response to the diet (Top panel) versus a hypoinsulinemic response due to partial genetic deletion of insulin alleles(Bottom panel). Top panel: A mouse model that responds to HFD with hyperinsulinemia displays similar effects as the response of wild type mice to HFD60: adipose expansion and inflammation, glucose intolerance, hepatic steatosis and hyperlipidemia. Expanded, inflamed adipose is thought to secondarily promote hepatic steatosis and gluconeogenesis. Bottom panel: A mouse model with one less insulin allele than that described in the top panel, which does not display hyperinsulinemia in response to HFD, shows little or no adipose expansion, glucose intolerance or hepatic steatosis under HFD conditions. In addition, adipose browning occurs with upregulation of uncoupling protein 1 and energy expenditure is increased under HFD feeding in this mouse model.