Fibroblast Growth Factor 21 Exerts its Anti‐inflammatory Effects on Multiple Cell Types of Adipose Tissue in Obesity

Abstract

Objective Obesity‐related, chronic, low‐grade inflammation has been identified as a key factor in the development of many metabolic diseases, such as type 2 diabetes and cardiovascular diseases. Adipocytes, preadipocytes, and macrophages have been implicated in initiating inflammation in adipose tissue. This study aims to investigate the effects of fibroblast growth factor‐21 (FGF‐21) on obesity‐related inflammation and its mechanisms in vivo and in vitro. Methods Monosodium glutamate (MSG) was used to induce obesity in mice and subsequently treated the mice with or without FGF‐21. Primary adipocytes and stromal vascular fraction cells were isolated from MSG‐obesity mice for additional experiments. Results Results obtained by ELISA and real‐time polymerase chain reaction showed that FGF‐21 efficiently ameliorated obesity‐related inflammation in MSG‐obesity mice. This study demonstrated that preadipocytes and adipocytes responded to anti‐inflammatory effects of FGF‐21. In vitro, 3 T3‐L1 preadipocytes lacking β‐klotho did not respond to FGF‐21 under glucose uptake. Interestingly, the treatment of 3 T3‐L1 preadipocytes with FGF‐21 significantly attenuated lipopolysaccharide‐induced inflammatory response. Conclusions Our study showed that FGF‐21–induced glucose uptake and FGF‐21–related anti‐inflammatory effects are mediated by different signaling pathways. Moreover, FGF‐21 showed anti‐inflammatory effects on preadipocytes; these effects are mediated by the fibroblast growth factor receptor substrate 2/ERK1/2 signaling pathway.

Vaspin in Serum and Urine of Post-Partum Women with Excessive Gestational Weight Gain

“…Nevertheless, these observations may be related to relationships that are not yet fully understood between vaspin and other adipokines, including the abovementioned FABP4. In light of the recent study by Wang et al [41], it seems to be very interesting to investigate associations between vaspin and fibroblast growth factor-21 (FGF-21) in future research. The authors demonstrated that FGF-21 alleviates inflammation and that the anti-inflammatory effects of FGF-21 are mediated by the fibroblast growth factor receptor substrate 2/extracellular signal-regulated kinase 1/2 (FRS2/ERK1/2) signaling pathway in 3T3-L1 preadipocytes.…”

FGF/FGFR signaling in health and disease

“…517 FGF21 has anti-inflammatory effect on preadipocytes via FRS2/ ERK1/2 signaling pathway. 518 Besides, FGF21 can suppress the production of IL-1β mediated by NLRP3 (NOD-, LRR-and pyrin domain-containing protein 3) inflammasome. 519 In general, inflammation increases the expression of FGF21, which is an anti-inflammatory factor in many diseases.…”

Adipokines and Inflammation: Focus on Cardiovascular Diseases

“…It is a secreted protein that acts mainly as an important endocrine metabolism regulator by inducing weight loss and controlling insulin signalling and glucose and lipid metabolism [ 316 ]. It was also described to have a well-characterised anti-inflammatory effect on different tissues/cells, including obese adipose tissue [ 320 , 321 ], liver [ 322 ], pancreas [ 323 ], lungs [ 324 ], heart [ 325 ], skeletal muscle [ 326 ], and macrophages [ 327 , 328 ].…”