Circulating fibroblast growth factor 21 is reduced, whereas its production is increased in a fat depot-specific manner in cold-acclimated rats.

This study investigated the effects of cold acclimation on circulating fibroblast growth factor 21 (FGF21) levels, as well as its production and signaling in classical brown and white adipose tissues. Male Wistar rats were cold (4°C) acclimatized for 7 days. Subsequently, liver, interscapular and aortic BAT (iBAT and aBAT), and the Sc Ing and epididymal (Epid) white adipose tissues were extracted. Cold acclimation significantly reduced circulating FGF21 and its liver expression. Conversely, FGF21 content increased in iBAT, aBAT and Sc Ing fat depots, along with the expressions of the Fgf21 receptor and the receptor co-factor β-klotho. Cold acclimation increased FGF21 secretion from Sc Ing and Epid adipocytes, although only iBAT and Sc Ing fat depots enhanced ERK1/2 phosphorylation. These findings provide evidence that FGF21 acts in an autocrine/paracrine manner in iBAT and Sc Ing fat depots under cold-acclimating conditions and may contribute to driving depot-specific thermogenic adaptive responses.