Endocrine FGFs and their signaling in the brain: Relevance for energy homeostasis

Dec 6, 2023European journal of pharmacology

Hormone-like FGFs and their brain signals linked to energy balance

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Abstract

Endocrine fibroblast growth factors (FGFs) are crucial regulators of metabolism during energy availability fluctuations.

FGF19, FGF21, and FGF23 are a unique subfamily of FGFs that act as hormones.
These endocrine FGFs are involved in regulating lipid, glucose, and energy metabolism.
FGF19 and FGF21 are associated with body weight loss and improved glucose control in both rodents and humans.
In contrast, increased levels of FGF23 have been linked to insulin resistance and obesity.
Emerging concepts suggest that endocrine FGF signaling in the brain may offer new therapeutic targets for metabolic disorders.

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Since their discovery in 2000, there has been a continuous expansion of studies investigating the physiology, biochemistry, and pharmacology of endocrine fibroblast growth factors (FGFs). FGF19, FGF21, and FGF23 comprise a subfamily with attributes that distinguish them from typical FGFs, as they can act as hormones and are, therefore, referred to as endocrine FGFs. As they participate in a broad cross-organ endocrine signaling axis, endocrine FGFs are crucial lipidic, glycemic, and energetic metabolism regulators during energy availability fluctuations. They function as powerful metabolic signals in physiological responses induced by metabolic diseases, like type 2 diabetes and obesity. Pharmacologically, FGF19 and FGF21 cause body weight loss and ameliorate glucose homeostasis and energy expenditure in rodents and humans. In contrast, FGF23 expression in mice and humans has been linked with insulin resistance and obesity. Here, we discuss emerging concepts in endocrine FGF signaling in the brain and critically assess their putative role as therapeutic targets for treating metabolic disorders.

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Endocrine FGFs and their signaling in the brain: Relevance for energy homeostasis

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