Abstract
This study aimed to investigate the effect of chronic treatment with the liver and fat‐derived hormone FGF21 on whole body and liver energy metabolism in Siberian hamsters in their seasonally fat state. Recombinant FGF21 (1 mg/kg/day) or saline (vehicle) were continuously infused for 14 days via subcutaneous, osmotic mini‐pumps. Body weight, ependymal white adipose tissue and hepatic triglyceride content were reduced (P<0.05) by 7%, 24% and 47% respectively in animals treated with FGF21. Whole body daily energy expenditure and fat oxidation increased (P<0.01) by 9% and 75% respectively. After FGF21 treatment, liver pyruvate dehydrogenase complex (PDC) activation, a key regulator of glucose oxidation, was reduced (P<0.05) by 35%, with a concomitant 30% increase (P<0.05) in long‐chain acylcarnitine accumulation reflecting enhanced fatty acid flux through β‐oxidation. There was an increase (P <0.05) in protein abundance of PGC1α and of two of its targets; PDK4, a molecular inhibitor of PDC, and pACC, which would increase fat oxidation. These findings suggest that FGF21‐induced upregulation of hepatic PGC1α mediates the shift in energy utilization from carbohydrate to fat. This mechanism serves to couple the FGF21‐induced modulation in nutrient flux to its known anti‐steatotic effect, and may contribute to increased energy expenditure and ultimately weight lossGrant Funding Source: BBSRC
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