FGF21 and the late adaptive response to starvation in humans

Fazeli, Pouneh K.; Lun, Mingyue; Kim, Soo M.; Bredella, Miriam A.; Wright, Spenser; Zhang, Yang; Lee, Hang; Catana, Ciprian; Klibanski, Anne; Patwari, Parth; Steinhauser, Matthew L.

doi:10.1172/jci83349

Cited by 183 publications

(175 citation statements)

References 48 publications

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“…In one recent study, a notable surge in FGF21 occurred after 7-10 days of fasting, and did not drive starvation-mediated ketogenesis like in mice [46]. Also, in humans FGF21 increment was stimulated after decreased thermogenesis, reduction in adiponectin levels, and tissue breakdown markers like transaminases elevation rather than changes in FFAs [46]. Nevertheless, several clinical studies have shown increment in FGF21 levels after other well-known inducers of supraphysiological concentrations of circulating FFAs different than prolonged fasting.…”

Section: Interventions That Modulates Fgf21 Synthesis and Secretionmentioning

confidence: 89%

Section: Interventions That Modulates Fgf21 Synthesis and Secretionmentioning

confidence: 93%

“…In mice, FGF21 is rapidly induced by fasting whereas in humans, fasting does not consistently increase FGF21 [44][45][46]. In one recent study, a notable surge in FGF21 occurred after 7-10 days of fasting, and did not drive starvation-mediated ketogenesis like in mice [46]. Also, in humans FGF21 increment was stimulated after decreased thermogenesis, reduction in adiponectin levels, and tissue breakdown markers like transaminases elevation rather than changes in FFAs [46].…”

Section: Interventions That Modulates Fgf21 Synthesis and Secretionmentioning

confidence: 98%

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Modulation of energy balance by fibroblast growth factor 21

Cuevas‐Ramos

Aguilar-Salinas

2016

Hormone Molecular Biology and Clinical Investigation

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Fibroblast growth factors (FGFs) are a superfamily of 22 proteins related to cell proliferation and tissue repair after injury. A subgroup of three proteins, FGF19, FGF21, and FGF23, are major endocrine mediators. These three FGFs have low affinity to heparin sulfate during receptor binding; in contrast they have a strong interaction with the cofactor Klotho/β-Klotho. FGF21 has received particular attention because of its key role in carbohydrate, lipids, and energy balance regulation. FGF21 improves glucose and lipids metabolism as well as increasing energy expenditure in animal models and humans. Conditions that induce human physical stress such as exercise, lactation, obesity, insulin resistance, and type 2 diabetes influence FGF21 circulating levels. FGF21 also has an anti-oxidant function in human metabolic diseases which contribute to understanding the FGF21 compensatory increment in obesity, the metabolic syndrome, and type 2 diabetes. Interestingly, energy expenditure and weight loss is induced by FGF21. The mechanism involved is through "browning" of white adipose tissue, increasing brown adipose tissue activity and heat production. Therefore, clinical evaluation of therapeutic action of exogenous FGF21 administration is warranted, particularly to treat diabetes and obesity.

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Section: Interventions That Modulates Fgf21 Synthesis and Secretionmentioning

confidence: 89%

Section: Interventions That Modulates Fgf21 Synthesis and Secretionmentioning

confidence: 93%

Section: Interventions That Modulates Fgf21 Synthesis and Secretionmentioning

confidence: 98%

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Modulation of energy balance by fibroblast growth factor 21

Cuevas‐Ramos

Aguilar-Salinas

2016

Hormone Molecular Biology and Clinical Investigation

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“…There were no specific dietary requirements for study participation, and subjects were not given specific instructions regarding diet. SAT biopsies were retrieved from the periumbilical region through the side wall of the umbilicus utilizing a Temno 14-gauge biopsy system (CareFusion) as described previously (40).…”

Section: Human Subjectsmentioning

confidence: 99%

Imaging mass spectrometry demonstrates age-related decline in human adipose plasticity

et al. 2017

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“…Several studies found that elevated blood concentrations of FGF21 were positively correlated with BMI (12–16), waist circumference (WC) (12,14,16,17), fat mass (13,16), or visceral adipose area (18,19), suggesting obesity as a FGF21-resistant state (20). A study also showed a significant association between circulating FGF21 levels and fasting-mediated weight loss in healthy subjects (21). …”

Section: Introductionmentioning

confidence: 96%

Macronutrient Intake–Associated FGF21 Genotype Modifies Effects of Weight-Loss Diets on 2-Year Changes of Central Adiposity and Body Composition: The POUNDS Lost Trial

Heianza

Huang

et al. 2016

Diabetes Care

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OBJECTIVEFibroblast growth factor 21 (FGF21) is involved in the regulation of energy balance and adipose metabolism. Our previous genome-wide association study identified genetic variants in the FGF21 region associated with macronutrient intake preference. We investigated whether the FGF21 genotype modified effects of weight-loss diets varying in macronutrient intake on changes in adiposity in a 2-year randomized diet intervention trial.RESEARCH DESIGN AND METHODSWe genotyped FGF21 rs838147 in 715 overweight or obese individuals who were assigned to one of four diets varying in macronutrient contents. A DEXA scan was performed to evaluate body composition.RESULTSWe observed a significant interaction between the FGF21 genotype and carbohydrate/fat intake on 2-year changes in waist circumference (WC), percentage of total fat mass, and percentage of trunk fat (P = 0.049, P = 0.001, and P = 0.003 for interaction, respectively). In response to the low-carbohydrate/high-fat diet, carrying the carbohydrate intake–decreasing C allele of rs838147 was marginally associated with less reduction in WC (P = 0.08) and significantly associated with less reduction of total fat mass (P = 0.01) and trunk fat (P = 0.02). Opposite genetic associations with these outcomes were observed among the high-carbohydrate/low-fat diet group; carrying the C allele was associated with a greater reduction of WC, total body fat mass, and trunk fat.CONCLUSIONSOur data suggest that FGF21 genotypes may interact with dietary carbohydrate/fat intake on changes in central adiposity and body fat composition. A low-calorie, high-carbohydrate/low-fat diet was beneficial for overweight or obese individuals carrying the carbohydrate intake–decreasing allele of the FGF21 variant to improve body composition and abdominal obesity.

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FGF21 and the late adaptive response to starvation in humans

Cited by 183 publications

References 48 publications

Modulation of energy balance by fibroblast growth factor 21

Modulation of energy balance by fibroblast growth factor 21

Imaging mass spectrometry demonstrates age-related decline in human adipose plasticity

Macronutrient Intake–Associated FGF21 Genotype Modifies Effects of Weight-Loss Diets on 2-Year Changes of Central Adiposity and Body Composition: The POUNDS Lost Trial

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