Role of fibroblast growth factor 21 in obesity-induced hypothalamic inflammation

Abstract

Obesity-induced hypothalamic inflammation is associated with neuronal dysfunction and implicated in metabolic dysregulation. Fibroblast growth factor 21 (FGF21) is known to be an important metabolic regulator with anti-inflammatory properties. In this study, we investigated the effects of FGF21 deficiency on obesity-induced hypothalamic inflammation and thermogenic responses. FGF21-deficient mice or wild-type mice were fed a high-fat diet (HFD) or a regular diet (RD) for twelve weeks. The FGF21-deficient mice fed an HFD showed increased levels of inflammatory cytokines (TNFα and IL-1β) accompanied by elevated gliosis markers (Iba-1 and GFAP) expression levels when compared with HFD-fed control mice. The level of HSP72 expression, a neuronal damage marker, was increased in the FGF21-deficient obese mice, and hypothalamic neuronal markers, such as orexigenic (NPY), anorexigenic (POMC), anti-thermogenic (MCH), and thermogenic (TRH) markers, were altered. The levels of UCP1 expression in brown adipose tissue (BAT) were reduced in FGF21-deficient obese mice when compared with HFD-fed control mice. These findings suggest that FGF21 deficiency aggravates obesity-induced hypothalamic inflammation and reduces thermogenic responses and that this is associated with alteration of the hypothalamic neural circuits. FGF21 may be useful as a therapeutic target for controlling obesity-induced hypothalamic inflammation and metabolic derangement.