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Fibroblast growth factor 21 action in the brain increases energy expenditure and insulin sensitivity in obese rats. | LitMetric

AI Article Synopsis

  • FGF21 is a hormone that can improve energy balance and insulin sensitivity in obese rats when administered directly into the brain.
  • In a study, obese rats received continuous FGF21 infusion for two weeks, leading to increased food intake and energy expenditure without significant changes in body weight or fat.
  • The infusion enhanced insulin sensitivity by reducing liver glucose production, suggesting that targeting the brain may be a promising approach to managing diabetes and obesity.

Article Abstract

Objective: The hormone fibroblast growth factor 21 (FGF21) exerts diverse, beneficial effects on energy balance and insulin sensitivity when administered systemically to rodents with diet-induced obesity (DIO). The current studies investigate whether central FGF21 treatment recapitulates these effects.

Research Design And Methods: After preliminary dose-finding studies, either saline vehicle or recombinant human FGF21 (0.4 microg/day) was infused continuously for 2 weeks into the lateral cerebral ventricle of male Wistar rats rendered obese by high-fat feeding. Study end points included measures of energy balance (body weight, body composition, food intake, energy expenditure, and circulating and hepatic lipids) and glucose metabolism (insulin tolerance test, euglycemic-hyperinsulinemic clamp, and hepatic expression of genes involved in glucose metabolism).

Results: Compared with vehicle, continuous intracerebroventricular infusion of FGF21 increased both food intake and energy expenditure in rats with DIO, such that neither body weight nor body composition was altered. Despite unchanged body fat content, rats treated with intracerebroventricular FGF21 displayed a robust increase of insulin sensitivity due to increased insulin-induced suppression of both hepatic glucose production and gluconeogenic gene expression, with no change of glucose utilization.

Conclusions: FGF21 action in the brain increases hepatic insulin sensitivity and metabolic rate in rats with DIO. These findings identify the central nervous system as a potentially important target for the beneficial effects of FGF21 in the treatment of diabetes and obesity.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2889784PMC
http://dx.doi.org/10.2337/db09-1878DOI Listing

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