Investigating the involvement of fibroblast growth factors in adipose tissue thermogenesis

Abstract

Objective: Thermogenesis in white and brown adipose tissues can be induced by various stimuli, including cold exposure, β-adrenergic stimulation, and tumor growth. Fibroblast growth factor (FGF) 21 has emerged as an important mediator of thermogenesis. This study investigated the involvement of other FGF family members in the regulation of adipose tissue thermogenesis. Materials and Methods: Mice were exposed to cold and administrated a β-adrenergic agonist (CL-316,243) to stimulate a thermogenic response in adipose tissues. Stromavascular fractions isolated from white and brown adipose tissues were cultured and differentiated into primary adipocytes. These cells were treated with recombinant FGFs. Changes in the expression levels of thermogenic genes and FGFs were determined by real-time quantitative PCR. Results: Cold exposure stimulated thermogenic gene expression in the adipose tissue, which was accompanied by the upregulation of certain FGFs. Ffg9 and Fgf21 were prominently induced in white and brown adipose tissues. β-adrenergic stimulation also upregulated thermogenic genes in adipocytes. Fgf21 was identified as the main responder to the β-adrenergic pathway. The administration of recombinant FGFs to cultured primary white and brown adipocytes induced thermogenic genes, including uncoupling protein-1 (Ucp1). FGF2, FGF9, and FGF21 triggered the most significant Ucp1-inducing effects in these cells. Conclusion: FGF21 is as a prominent inducer of thermogenesis in adipose tissue and a promising therapeutic target against cardiovascular and metabolic diseases. FGF2 and FGF9 potently promote thermogenic gene expression in adipocytes. Therefore, their therapeutic targeting should be considered to enhance energy metabolism in adipose tissues.