Loss of Nr4a3 results in increased adipose mass and impaired adipocyte respiration

Diabetes is a chronic disease that affects millions of people and will affect millions more in the coming generation. Symptoms of type 2 diabetes (T2D) include weight gain, impaired glucose tolerance, and impaired insulin secretion. Nuclear receptor Nr4a3 controls gene expression of targets essential for fuel metabolism and respiration. In patients with type 2 diabetes Nr4a3 promoter is hypermethylated, and Nr4a3 expression is downregulated. Here we demonstrate the effect of systemic Nr4a3 loss. Full body Nr4a3 KO animals were fed a standard diet. Male, but not female, Nr4a3 KO mice demonstrate impaired glucose and insulin tolerance. Male Nr4a3 KO mice have normal muscle, liver, and kidney respiration rates, while adipose tissue respiration is impaired. The impaired adipose respiration corresponds with increased mass of all adipose depots, increased adipocyte size, and increased lipid droplet size. Our data demonstrate the critical role of Nr4a3 in adipose tissue. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.