FGF21 is dispensable for hypothermia induced by fasting in mice.

ABSTRACT

BACKGROUND: Fibroblast growth factor 21 (FGF21) is a key metabolic regulator that is induced by peroxisome proliferator-activated receptor alpha (PPARalpha) activation in response to fasting. We recently reported that bezafibrate, a pan-agonist of PPARs, decreases body temperature late at night through hypothalamic neuropeptide Y (NPY) activation and others have shown that mice overexpressing FGF21 are prone to torpor. OBJECTIVES: We examined whether FGF21 is essential for fasting-induced hypothermia using FGF21 knockout (KO) mice. RESULTS: Acute fasting decreased body temperature late at night accompanied by the induction of hepatic FGF21 and hypothalamic NPY expression in wild-type mice. A deficiency of FGF21 affected neither fasting-induced hypothermia nor hypothalamic NPY induction. Fasting enhanced locomotor activity in both genotypes. On the other hand, a deficiency of FGF21 significantly attenuated chronic hypothermia and hypoactivity induced by a ketogenic diet (KD). CONCLUSIONS: Our findings suggest that FGF21 is not essential for the hypothermia that is associated with the early stages of fasting, although it might be involved in the adaptive response of body temperature to chronic starvation.