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Conditions in which energy supply from fat oxidation exceeds energy demand lead to formation of reactive oxygen species, in turn causing oxidative stress ( Preclinical characterization of FGF21 in rodents and primates has established its role in restoring metabolic homeostasis in obese or metabolically challenged animals, reducing body weight, liver and circulating triglycerides, fasting plasma insulin and glucose, and increasing energy expenditure ( While decreased FGF21 receptor expression has been proposed to underlie this FGF21-resistant state, ( Fibroblast Growth Factor 21 Physiology FGF21 relies on its obligate co-receptor, -Klotho, for recruitment to the extracellular surface of plasma membrane ( via pathways including the mitogen-activated protein kinase (MAPK) and AKT signaling networks ( Endocrine Role of Fibroblast Growth Factor 21 Physiology Because FGF21 enters the systemic circulation, it is able to integrate metabolism across liver, adipose tissue, skeletal muscle, pancreas, and other metabolic organs ( Figure 2 ), by controlling expression of transcriptional programs that shape cellular phenotype and tissue metabolic function, ultimately exerting anti-obesity, anti-diabetic, and anti-hyperlipidemic effects in rodents and primates ( Figure 2 Expression of FGF21 is regulated by metabolic cues

10.1016/S0140-6736(18)30478-1 Lancet 14 DomnguezC.LpezA.Ramos-CabrerP.Vieites-PradoA.Prez-MatoM.VillalbaC.et al (2019)

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