Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis

BonDurant, Lucas D.; Potthoff, Matthew J.

doi:10.1146/annurev-nutr-071816-064800

Cited by 161 publications

(155 citation statements)

References 155 publications

(321 reference statements)

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“…FGF21 is induced at the transcriptional level and released from murine liver in response to a remarkable diversity of nutritional stresses, including starvation, amino acid restriction, ketogenic and high-fat diets, simple sugars, and ethanol (BonDurant and Potthoff, 2018;. Among the transcription factors involved in FGF21 induction are PPARa, which induces FGF21 in response to starvation and ketogenic diet (Badman et al, 2007;Inagaki et al, 2007), and ChREBP, which induces FGF21 in response to simple sugars Iroz et al, 2017).…”

Section: Fgf21mentioning

confidence: 99%

A Dozen Years of Discovery: Insights into the Physiology and Pharmacology of FGF21

2019

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It has been more than a dozen years since FGF21 burst on the metabolism field in a paper showing that its pharmacologic administration caused weight loss and improved insulin sensitivity and lipoprotein profiles in obese rodents. Since then, FGF21 analogs have advanced all the way to clinical trials, and much progress has been made in understanding FGF21's pharmacology and physiology. In this Perspective, we highlight some of the interesting themes that have emerged from this first dozen years of FGF21 research, including its roles in autocrine/paracrine and endocrine responses to metabolic stress.

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Section: Fgf21mentioning

confidence: 99%

A Dozen Years of Discovery: Insights into the Physiology and Pharmacology of FGF21

2019

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“…In recent years, several exclusively or predominantly liver-secreted proteins, termed hepatokines, have been identified as molecules possessing the capacity to exert potent metabolic effects, both locally and distally (Meex et al 2015). These include fibroblast growth factor 21 (FGF21), shown to modulate glucose and lipid metabolism (Kharitonenkov et al 2005, Potthoff et al 2009, Xu et al 2009, BonDurant and Potthoff 2018; follistatin, demonstrated to regulate muscle growth (Amthor et al 2004, Yaden et al 2014 and influence pancreatic beta cell function and survival (Zhao et al 2015, Hansen et al 2016a; and leukocyte cell-derived chemotaxin 2 (LECT2), which can promote both skeletal muscle and adipose tissue insulin resistance (Lan et al 2014, Jung et al 2018.…”

Section: Introductionmentioning

confidence: 99%

Effect of exercise intensity on circulating hepatokine concentrations in healthy men

Willis

Sargeant

Thackray

et al. 2019

Appl. Physiol. Nutr. Metab.

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Fibroblast growth factor 21 (FGF21), follistatin and leukocyte cell-derived chemotaxin 2 (LECT2) are novel hepatokines that are modulated by metabolic stresses. This study investigated whether exercise intensity modulates the hepatokine response to acute exercise. Ten young, healthy men undertook three 8-h experimental trials: moderate-intensity exercise (MOD; 55% peak oxygen uptake), high-intensity exercise (HIGH; 75% peak oxygen uptake), and control (CON; rest), in a randomised, counterbalanced order. Exercise trials commenced with a treadmill run of varied duration to match gross exercise energy expenditure between trials (MOD vs HIGH; 2475 ± 70 vs 2488 ± 58 kJ). Circulating FGF21, follistatin, LECT2, glucagon, insulin, glucose and nonesterified fatty acids (NEFA) were measured before exercise and at 0, 1, 2, 4, and 7 h postexercise. Plasma FGF21 concentrations were increased up to 4 h postexercise compared with CON (P ≤ 0.022) with greater increases observed at 1, 2, and 4 h postexercise during HIGH versus MOD (P ≤ 0.025). Irrespective of intensity (P ≥ 0.606), plasma follistatin concentrations were elevated at 4 and 7 h postexercise (P ≤ 0.053). Plasma LECT2 concentrations were increased immediately postexercise (P ≤ 0.046) but were not significant after correcting for plasma volume shifts. Plasma glucagon (1 h; P = 0.032) and NEFA (4 and 7 h; P ≤ 0.029) responses to exercise were accentuated in HIGH versus MOD. These findings demonstrate that acute exercise augments circulating FGF21 and follistatin. Exercise-induced changes in FGF21 are intensity-dependent and may support the greater metabolic benefit of high-intensity exercise.

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“…Fibroblast growth factor 21 (FGF21), a regulator of energy metabolism, is mainly expressed and secreted by the liver, but other tissues, such as white and brown adipose tissue, skeletal muscle and cardiac muscle, also express and secrete FGF21 under certain circumstances in humans [1][2][3]. Whether FGF21 from these tissues contributes to circulating FGF21 concentrations and under what conditions is less clear [1]. Plasma concentrations of FGF21 are increased in human obesity.…”

Section: Introductionmentioning

confidence: 99%

Adipose tissue contribution to plasma fibroblast growth factor 21 and fibroblast activation protein in obesity

et al. 2019

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Fibroblast growth factor 21 (FGF21) is an important regulator of energy metabolism. FGF21 is inactivated by fibroblast activation protein (FAP). We investigated whether FGF21 and/or FAP are secreted from human white adipose tissue of individuals with obesity by measuring total FGF21, active FGF21, and FAP concentrations in arterialized blood and venous blood draining the subcutaneous abdominal adipose tissue (scAT). Measurements were performed under fasting conditions and after a high fat meal before and after diet-induced weight loss in 16 adults with BMI 27-35 kg/m 2. FGF21 was not released from scAT, neither before nor after weight loss in agreement with an undetectable gene expression of FGF21 in this tissue. Although scAT showed significant gene expression of FAP, no release of FAP from the tissue could be detected. The high fat meal increased postprandial circulating FGF21 but not FAP. Circulating levels of FAP but not FGF21 were significantly reduced after weight loss. On the other hand, FAP expression in scAT was increased. In conclusion, release from scAT does not appear to contribute to circulating concentrations of FGF21 and FAP and their responses to ingestion of a high fat meal or weight loss, respectively, in individuals with obesity.

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Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis

Cited by 161 publications

References 155 publications

A Dozen Years of Discovery: Insights into the Physiology and Pharmacology of FGF21

A Dozen Years of Discovery: Insights into the Physiology and Pharmacology of FGF21

Effect of exercise intensity on circulating hepatokine concentrations in healthy men

Adipose tissue contribution to plasma fibroblast growth factor 21 and fibroblast activation protein in obesity

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