We propose that Fgf21 methylation represents a form of epigenetic memory that persists into adulthood, and it may have a role in the developmental programming of obesity.
We tested whether a targeted reduction in hepatic peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), which has been shown to occur with obesity, had a negative impact on the metabolic effects of FGF21.
Here, we show that chronic PD retards the development of hypertrigylceridemia and fatty liver in obesity and that this relies on the induction of the hepatokine fibroblast growth factor 21 (FGF21).
These anti-inflammatory cytokines are decreased (adiponectin, omentin, and osteocalcin) or increased (leptin, FGF-21, and irisin) in obesity suggesting a resistance state.
Remarkably, VCE-004.8 increased the FGF21 mRNA expression in white and brown adipose, as well as in a BAT cell line, qualifying cannabinoaminoquinones as a class of novel therapeutic candidates for the management of obesity and its common metabolic co-morbidities.
Numerous studies have been conducted to establish and confirm whether FGF21 exerts beneficial effects on obesity and diabetes along with its complications.
Fasted (resting) FGF21 and LECT2 were higher in overweight/obese individuals (129% and 55%; P ≤ 0.01) and correlated with indices of adiposity and insulin resistance; whereas circulating follistatin was lower in overweight/obese individuals throughout trial days (17%, P < 0.05).
These data identify Plin2 actions as novel mediators of sugar-induced adipose browning through indirect effects of hepatic FGF21 expression, and suggest that adipose browning mechanisms may contribute to Plin2-null resistance to obesity.
Moreover, despite the metabolic health-promoting effects of FGF21, the levels of this hormone are increased under conditions such as obesity and diabetes, an apparent incongruity that has been attributed to altered tissue responsiveness to FGF21.
Obese non-diabetic rhesus macaque monkeys (five males and five ovariectomized (OVX) females) were maintained on a high-fat diet and treated for 12 weeks with escalating doses of FGF21.
Glucose kinetics and plasma FGF19 and FGF21 responses to mixed meal ingestion and to glucose-insulin infusion during a hyperinsulinemic-euglycemic clamp procedure, with stable isotope tracer methods, were evaluated in 28 adults with obesity before and after 20% weight loss induced by RYGB (n = 16) or LAGB (n = 12).
Continuous intracerebroventricular (i.c.v.) administration of FGF21 was found to modulate feeding and energy expenditure in rats with diet-induced obesity, suggesting a central effect by the peptide.
This review summarizes what is known about FGF21 in mice and humans with a special focus on this factor's role in glucose and lipid metabolism and in metabolic diseases, such as obesity and type 2 diabetes mellitus.
Moreover, here we describe an approach to increase the endogenous production of FGF21, which if demonstrated functional in humans, could generate a treatment for obesity.
This is in contrast to the anti-diabetic medication metformin and suggests that the treatment of obesity and diabetes with the combination of FGF21 and AMPK activators merits consideration.
FGF1, FGF10, FGF15/FGF19 and FGF21) have been further recognized as regulators of energy homeostasis, metabolism and adipogenesis, constituting novel therapeutic targets for obesity and obesity-related cardiometabolic disease.
Fibroblast growth factor 21 (FGF21) is a potent endocrine regulator with physiological effects on glucose and lipid metabolism and thus garners much attention for its translational potential for the management of obesity and related metabolic syndromes.
Insulin increased serum and muscle FGF21 independent of overweight/obesity or type 2 diabetes, and there were no effects associated with exercise training.
Circulating serum FGF19 concentrations were decreased (P < 0.01) similarly in obese patients regardless of their degree of insulin resistance, while FGF21 levels were increased in obesity (P < 0.01), being further increased in obesity-associated T2D (P < 0.01).