Burning Fat and Building Bone by FSH Blockade

Abstract

The rise of follicle-stimulating hormone (FSH) is a hallmark of menopause associated with osteoporosis and visceral adiposity. In Nature, Zaidi and colleagues (Liu et al., 2017) report that blocking FSH action reduces body fat by promoting brown/beige fat thermogenesis, potentially providing a new intervention for the treatment of menopause-related metabolic diseases.

Figure 1.. The Role of Follicle-Stimulating Hormone in Osteoclasts and Adipocytes

(A and B) Follicle-stimulating hormone (FSH) activates FSH receptor (FSH-R) that is coupled to the inhibitory G protein (Gi). (A) In menopause, increased FSH levels in the circulation trigger several signaling pathways in osteoclasts, such as MEK/Erk, Akt, and NF-κB, leading to the activation of osteoclastogenesis and bone reabsorption. In adipocytes, activation of the Gi protein via FSH-R decreases cAMP levels and thermogenic gene expression. (B) When the FSH signaling is blocked by a neutralizing antibody, osteoclast activity and subsequent bone reabsorption are inhibited. In adipocytes, the FSH antibody also activates brown/beige fat thermogenesis through promoting UCP1 expression.