Loss in ATE1 may affect energy metabolism through leptin

Kopchenko, Nicholas
Alkhatatbeh, Mosleh
Brower, Christopher
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Arginyl-tRNA protein transferase 1 (ATE1) regulates protein degradation by Arg/N-end rule pathway. Previous studies have shown that downregulation of ATE1 can lead to neurodegeneration, behavioral abnormalities, hyperphagia and lower body weight. To determine how loss of ATE1 affects energy metabolism and food intake, ATE1-deficient and ATE1-containing mice were given high fat diet for 6-8 weeks. Based on our current data, we found significant sex differences in body weight and food intakes, with ATE1-deficient mice less sensitive to the obesogenic effects of high fat diet even while consuming the same amount of high fat diet as controls. Interestingly, ATE1-deficient mice exposed to high fat diet displayed lower plasma leptin levels even after normalizing to white adipose tissue (WAT) weight. We also show sex differences in ATE1-deficient female mice given acute leptin treatment. Taken together, these data indicate that loss of ATE1 affects leptin levels independent of WAT but may alter leptin sensitivity in ATE1-deficient mice.