Skip to main content
. 2022 Aug 2;9:962561. doi: 10.3389/fcvm.2022.962561

Figure 1.

Figure 1

FGF21-FGFR1/β-KL regulation of multi-organ crosstalk under metabolic stress. FGF21-FGFR1/β-KL signaling is vital in regulating systemic and organ responses under pathophysiological metabolic stress. Hepatic sourced FGF21 (circle) reduces ketone metabolism in the cardiomyocytes, induces secretion of adiponectin from WAT, and modulates systemic metabolism. Moreover, hepatic sourced FGF21 passes through the blood-brain barrier and is involved in regulation of circadian rhythm and appetite response. In a feedback loop, β-KL signaling in the VMH-specific glutamatergic neurons contributes to modulating hepatic nutrient uptake. The release of CRF and corticosterone from the brain is responsible for regulating energy expenditure in the adipose tissue and liver gluconeogenesis, respectively. Cardiac sourced FGF21 (triangle) promotes thermogenesis in the adipose tissue, thus improving overall metabolic health. Under the adipo-hepatic communication, reduced expression of adipose FGFR1 aggravates hepatic steatosis and adipose FGF21 (square) increases the expression of hepatic FGF21. Hence, multi-organ crosstalk mediated by FGF21-FGFR1/β-KL signaling alleviates metabolic distress by improving insulin sensitivity, glucose, and lipid levels in the body, along with increased energy expenditure in the adipose tissue and weight loss. BAT, brown adipose tissue; β-KL, beta-klotho; CRF, corticotropin releasing factor; FGF21, fibroblast growth factor 21; FGFR1, fibroblast growth factor receptor 1; VMH, ventromedial hypothalamus; WAT, white adipose tissue (created with Biorender.com).