FGF21 Signals to Glutamatergic Neurons in the Ventromedial Hypothalamus to Suppress Carbohydrate Intake

Fibroblast growth factor 21 (FGF21) is an endocrine hormone produced by the liver that regulates nutrient and metabolic homeostasis. FGF21 production is increased in response to macronutrient imbalance and signals to the brain to suppress sugar intake and sweet-taste preference. However, the central...

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Published in:Cell metabolism Vol. 32; no. 2; p. 273
Main Authors: Jensen-Cody, Sharon O, Flippo, Kyle H, Claflin, Kristin E, Yavuz, Yavuz, Sapouckey, Sarah A, Walters, Grant C, Usachev, Yuriy M, Atasoy, Deniz, Gillum, Matthew P, Potthoff, Matthew J
Format: Journal Article
Language:English
Published: United States 04.08.2020
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ISSN:1932-7420, 1932-7420
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Abstract Fibroblast growth factor 21 (FGF21) is an endocrine hormone produced by the liver that regulates nutrient and metabolic homeostasis. FGF21 production is increased in response to macronutrient imbalance and signals to the brain to suppress sugar intake and sweet-taste preference. However, the central targets mediating these effects have been unclear. Here, we identify FGF21 target cells in the hypothalamus and reveal that FGF21 signaling to glutamatergic neurons is both necessary and sufficient to mediate FGF21-induced sugar suppression and sweet-taste preference. Moreover, we show that FGF21 acts directly in the ventromedial hypothalamus (VMH) to specifically regulate sucrose intake, but not non-nutritive sweet-taste preference, body weight, or energy expenditure. Finally, our data demonstrate that FGF21 affects neuronal activity by increasing activation and excitability of neurons in the VMH. Thus, FGF21 signaling to glutamatergic neurons in the VMH is an important component of the neurocircuitry that functions to regulate sucrose intake.
AbstractList Fibroblast growth factor 21 (FGF21) is an endocrine hormone produced by the liver that regulates nutrient and metabolic homeostasis. FGF21 production is increased in response to macronutrient imbalance and signals to the brain to suppress sugar intake and sweet-taste preference. However, the central targets mediating these effects have been unclear. Here, we identify FGF21 target cells in the hypothalamus and reveal that FGF21 signaling to glutamatergic neurons is both necessary and sufficient to mediate FGF21-induced sugar suppression and sweet-taste preference. Moreover, we show that FGF21 acts directly in the ventromedial hypothalamus (VMH) to specifically regulate sucrose intake, but not non-nutritive sweet-taste preference, body weight, or energy expenditure. Finally, our data demonstrate that FGF21 affects neuronal activity by increasing activation and excitability of neurons in the VMH. Thus, FGF21 signaling to glutamatergic neurons in the VMH is an important component of the neurocircuitry that functions to regulate sucrose intake.
Fibroblast growth factor 21 (FGF21) is an endocrine hormone produced by the liver that regulates nutrient and metabolic homeostasis. FGF21 production is increased in response to macronutrient imbalance and signals to the brain to suppress sugar intake and sweet-taste preference. However, the central targets mediating these effects have been unclear. Here, we identify FGF21 target cells in the hypothalamus and reveal that FGF21 signaling to glutamatergic neurons is both necessary and sufficient to mediate FGF21-induced sugar suppression and sweet-taste preference. Moreover, we show that FGF21 acts directly in the ventromedial hypothalamus (VMH) to specifically regulate sucrose intake, but not non-nutritive sweet-taste preference, body weight, or energy expenditure. Finally, our data demonstrate that FGF21 affects neuronal activity by increasing activation and excitability of neurons in the VMH. Thus, FGF21 signaling to glutamatergic neurons in the VMH is an important component of the neurocircuitry that functions to regulate sucrose intake.Fibroblast growth factor 21 (FGF21) is an endocrine hormone produced by the liver that regulates nutrient and metabolic homeostasis. FGF21 production is increased in response to macronutrient imbalance and signals to the brain to suppress sugar intake and sweet-taste preference. However, the central targets mediating these effects have been unclear. Here, we identify FGF21 target cells in the hypothalamus and reveal that FGF21 signaling to glutamatergic neurons is both necessary and sufficient to mediate FGF21-induced sugar suppression and sweet-taste preference. Moreover, we show that FGF21 acts directly in the ventromedial hypothalamus (VMH) to specifically regulate sucrose intake, but not non-nutritive sweet-taste preference, body weight, or energy expenditure. Finally, our data demonstrate that FGF21 affects neuronal activity by increasing activation and excitability of neurons in the VMH. Thus, FGF21 signaling to glutamatergic neurons in the VMH is an important component of the neurocircuitry that functions to regulate sucrose intake.
Author Walters, Grant C
Usachev, Yuriy M
Gillum, Matthew P
Atasoy, Deniz
Yavuz, Yavuz
Flippo, Kyle H
Claflin, Kristin E
Sapouckey, Sarah A
Potthoff, Matthew J
Jensen-Cody, Sharon O
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  givenname: Sharon O
  surname: Jensen-Cody
  fullname: Jensen-Cody, Sharon O
  organization: Department of Neuroscience and Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA; Fraternal Order of Eagles Diabetes Research Center, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA; Iowa Neuroscience Institute, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA
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  givenname: Kyle H
  surname: Flippo
  fullname: Flippo, Kyle H
  organization: Department of Neuroscience and Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA; Fraternal Order of Eagles Diabetes Research Center, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA; Iowa Neuroscience Institute, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA
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  givenname: Kristin E
  surname: Claflin
  fullname: Claflin, Kristin E
  organization: Department of Neuroscience and Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA; Fraternal Order of Eagles Diabetes Research Center, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA; Iowa Neuroscience Institute, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA
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  surname: Yavuz
  fullname: Yavuz, Yavuz
  organization: Department of Neuroscience and Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA; Fraternal Order of Eagles Diabetes Research Center, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA; Iowa Neuroscience Institute, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA
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  givenname: Sarah A
  surname: Sapouckey
  fullname: Sapouckey, Sarah A
  organization: Department of Neuroscience and Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA; Fraternal Order of Eagles Diabetes Research Center, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA; Iowa Neuroscience Institute, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA
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  givenname: Grant C
  surname: Walters
  fullname: Walters, Grant C
  organization: Department of Neuroscience and Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA; Fraternal Order of Eagles Diabetes Research Center, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA; Iowa Neuroscience Institute, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA
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  givenname: Yuriy M
  surname: Usachev
  fullname: Usachev, Yuriy M
  organization: Department of Neuroscience and Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA; Fraternal Order of Eagles Diabetes Research Center, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA; Iowa Neuroscience Institute, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA
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  givenname: Deniz
  surname: Atasoy
  fullname: Atasoy, Deniz
  organization: Department of Neuroscience and Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA; Fraternal Order of Eagles Diabetes Research Center, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA; Iowa Neuroscience Institute, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA
– sequence: 9
  givenname: Matthew P
  surname: Gillum
  fullname: Gillum, Matthew P
  email: gillum@sund.ku.dk
  organization: Section for Nutrient and Metabolite Sensing, the Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, 2200 Copenhagen, Denmark. Electronic address: gillum@sund.ku.dk
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  organization: Department of Neuroscience and Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA; Fraternal Order of Eagles Diabetes Research Center, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA; Iowa Neuroscience Institute, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA; Department of Veterans Affairs Medical Center, Iowa City, IA 52242, USA. Electronic address: matthew-potthoff@uiowa.edu
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liver
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sugar intake
sweet-taste preference
brain
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glucose sensing
hypothalamus
FGF21
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References 32690916 - Nat Rev Endocrinol. 2020 Sep;16(9):472
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Title FGF21 Signals to Glutamatergic Neurons in the Ventromedial Hypothalamus to Suppress Carbohydrate Intake
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