FGF21 as a mediator of adaptive responses to stress and metabolic benefits of anti-diabetic drugs

Abstract

Most hormones secreted from specific organs of the body in response to diverse stimuli contribute to the homeostasis of the whole organism. Fibroblast growth factor 21 (FGF21), a hormone induced by a variety of environmental or metabolic stimuli, plays a crucial role in the adaptive response to these stressful conditions. In addition to its role as a stress hormone, FGF21 appears to function as a mediator of the therapeutic effects of currently available drugs and those under development for treatment of metabolic diseases. In this review, we highlight molecular mechanisms and the functional importance of FGF21 induction in response to diverse stress conditions such as changes of nutritional status, cold exposure, and exercise. In addition, we describe recent findings regarding the role of FGF21 in the pathogenesis and treatment of diabetes associated with obesity, liver diseases, pancreatitis, muscle atrophy, atherosclerosis, cardiac hypertrophy, and diabetic nephropathy. Finally, we discuss the current understanding of the actions of FGF21 as a crucial regulator mediating beneficial metabolic effects of therapeutic agents such as metformin, glucagon/glucagonlike peptide 1 analogues, thiazolidinedione, sirtuin 1 activators, and lipoic acid.

Lipodystrophy HIV-related and FGF21: A new marker to follow the progression of lipodystrophy?

“…Moreover, adipose tissue showed a large high expression of FGF receptor 1 [32] and emerged as a strong candidate to represent a predominant FGF21 target tissue. This new evidence about FGF21 highlights the opportunities to target this molecule for new pharmaceutical formulations to combat type 2 diabetes and metabolic syndrome [20] and that a rise in circulating FGF21 has been proposed as a predictor of the development of the metabolic syndrome and type 2 diabetes mellitus [33] . We decided to propose this hormone as a marker of metabolic and morphological alterations in the patient with HIV-related lipodystrophy in order to monitor the efficacy of the proposed interventions (drugs, modification of lifestyle, and different supplements).…”

“…It seems clear today that FGF21 acts in synergy with other hormones with metabolic action as insulin, glucagon, leptin, glucagon-like peptide, adiponectin, growth hormone, glucagon-like peptide 1 (GLP1), and insulin-like growth factor 1 (IGF1) and then it seems logical to think of a potential therapeutic role in the metabolic syndrome or in overt diabetes [20] .…”

Fibroblast growth factor 21 and its novel association with oxidative stress

“…FGF21 appears to be a mediator of the therapeutic effects of drugs involved in the treatment of some metabolic diseases [84]. Metformin reduces the plasma glucose concentration through the inhibition of glucose absorption in the intestine, suppression of gluconeogenesis in the liver and the improvement of the insulin action in the periphery [85].…”

Pharmacologic stimulation of central GLP-1 receptors has opposite effects on the alterations of plasma FGF21 levels induced by feeding and fasting

“…variety of environmental and metabolic stimuli including changes of nutritional status and mediates the adaptive responses to stress [2]. Circulating FGF21 is derived from liver and is produced during fasting and feeding [3].…”