Fibroblast Growth Factor-21 Controls Dietary Protein Intake in Male Mice

Larson, Karlton R.; Chaffin, Aki T.B.; Goodson, Michael L.; Fang, Yong; Ryan, Karen K.

doi:10.1210/en.2018-01056

Cited by 53 publications

(61 citation statements)

References 73 publications

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“…Finally, we demonstrate that ICV injection of FGF21 recapitulates this casein preference in WT, chow-fed mice but not in mice lacking Klb expression in the brain. This latter observation is highly consistent with a very recently published study demonstrating that FGF21 injection selectively increased protein intake relative to carbohydrate or fat intake and that this effect required central Klb ( Larson et al, 2019 ). Collectively, these data provide compelling evidence that brain FGF21 signaling mediates a physiologically relevant, adaptive change in macronutrient preference.…”

Section: Discussionsupporting

confidence: 91%

FGF21 Signals Protein Status to the Brain and Adaptively Regulates Food Choice and Metabolism

et al. 2019

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Section: Discussionsupporting

confidence: 91%

FGF21 Signals Protein Status to the Brain and Adaptively Regulates Food Choice and Metabolism

et al. 2019

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“…Thus, our findings identify dissociable aspects of the metabolic effects of dietary protein restriction and suggest FGF21 signaling is required in multiple tissues to prevent metabolic dysfunction during macronutrient imbalance. www.nature.com/scientificreports/ In addition to energy expenditure and body weight regulation, FGF21 induction by low protein diets has been proposed to regulate protein intake 16,38 . Our three-bottle choice experiments with different protein and carbohydrate concentrations revealed that FGF21 primarily regulates simple sugar intake, not protein preference.…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, sucrose intake was significantly suppressed during FGF21 administration in all groups receiving sucrose and the response was reversed during the washout period. In addition, a previous study by Larson et al compared FGF21-mediated preferences in diets with different macronutrient composition 38 . However, this approach is not adequate to accurately assess taste preferences 39,40 .…”

Section: Discussionmentioning

confidence: 99%

FGF21 signaling in glutamatergic neurons is required for weight loss associated with dietary protein dilution

Flippo

Jensen-Cody

Claflin

et al. 2020

Sci Rep

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Alterations in macronutrient intake can have profound effects on energy intake and whole-body metabolism. For example, reducing protein intake increases energy expenditure, increases insulin sensitivity and decreases body weight in rodents. Fibroblast growth factor 21 (FGF21) signaling in the brain is necessary for the metabolic effects of dietary protein restriction and has more recently been proposed to promote protein preference. However, the neuron populations through which FGF21 elicits these effects are unknown. Here, we demonstrate that deletion of β-klotho in glutamatergic, but not GABAergic, neurons abrogated the effects of dietary protein restriction on reducing body weight, but not on improving insulin sensitivity in both diet-induced obese and lean mice. Specifically, FGF21 signaling in glutamatergic neurons is necessary for protection against body weight gain and induction of UCP1 in adipose tissues associated with dietary protein restriction. However, β-klotho expression in glutamatergic neurons was dispensable for the effects of dietary protein restriction to increase insulin sensitivity. In addition, we report that FGF21 administration does not alter protein preference, but instead promotes the foraging of other macronutrients primarily by suppressing simple sugar consumption. This work provides important new insights into the neural substrates and mechanisms behind the endocrine control of metabolism during dietary protein dilution.

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“…In a recent report, FGF21 has been shown to inhibit sucrose intake as well as promote the relative rejection of low-protein diets containing high amounts of either carbohydrate or fat and matched for sweetness, suggesting that FGF21 directly stimulates protein intake under certain conditions (Larson et al 2019). However, FGF21 reduces preference for the non-caloric sweetener sucralose in mice with simultaneous access to regular chow, without increasing protein, fat or complex carbohydrate consumption.…”

Section: Low-protein Diets In Combination With High Carbohydrate Maximentioning

confidence: 99%

Fibroblast growth factor 21: an endocrine inhibitor of sugar and alcohol appetite

Holstein-Rathlou

Gillum

2019

The Journal of Physiology

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Fibroblast growth factor 21 (FGF21) is a liver‐derived hormone with pleiotropic metabolic effects. Its production is induced by various dietary imbalances in mice (including low‐protein and ketogenic diets, fructose feeding and ethanol), hinting that it might influence food preference given the role of the liver in maintaining homeostatic levels of circulating nutrients. In 2016, it was shown that FGF21 selectively inhibits consumption of sugars and the primary product of their fermentation, ethanol, but not intake of fat, protein or complex carbohydrates. Since then, studies have sought to unravel this selectivity, its physiological purpose and translational relevance, as well as delineate the neural mechanisms involved. Initially found to impact ingestive behaviours in mice and non‐human primates, FGF21 is also induced in humans by sugars and, far more dramatically, by acute alcohol intake. Genetic studies have revealed that patterns of weekly candy and alcohol consumption are associated with genetic variants in FGF21 and its co‐receptor β‐klotho (KLB), suggesting that liking for sugar, and fermented sugar, may be influenced by natural variation in FGF21 signal strength in humans. Herein, we discuss our nascent understanding of FGF21 as a selective negative regulator of sugar and alcohol appetite as well as reasons why such a peculiar system may have evolved in mammals. Uncovering the regulatory network governing sugar, and fermented sugar, intake could provide new opportunities to improve dietary choices in a population suffering from Western diet‐induced diseases fuelled in part by a runaway sweet – and alcohol – tooth.

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Fibroblast Growth Factor-21 Controls Dietary Protein Intake in Male Mice

Cited by 53 publications

References 73 publications

FGF21 Signals Protein Status to the Brain and Adaptively Regulates Food Choice and Metabolism

FGF21 Signals Protein Status to the Brain and Adaptively Regulates Food Choice and Metabolism

FGF21 signaling in glutamatergic neurons is required for weight loss associated with dietary protein dilution

Fibroblast growth factor 21: an endocrine inhibitor of sugar and alcohol appetite

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