Journal article
FGF21 signaling in glutamatergic neurons is required for weight loss associated with dietary protein dilution
Scientific reports, Vol.10(1), pp.19521-19521
11/11/2020
DOI: 10.1038/s41598-020-76593-2
PMCID: PMC7658965
PMID: 33177640
Abstract
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.
Details
- Title: Subtitle
- FGF21 signaling in glutamatergic neurons is required for weight loss associated with dietary protein dilution
- Creators
- Kyle H Flippo - Iowa Neuroscience Institute, University of Iowa Carver College of Medicine, Iowa City, IA, 52242, USASharon O Jensen-Cody - Iowa Neuroscience Institute, University of Iowa Carver College of Medicine, Iowa City, IA, 52242, USAKristin E Claflin - Iowa Neuroscience Institute, University of Iowa Carver College of Medicine, Iowa City, IA, 52242, USAMatthew J Potthoff - Department of Veterans Affairs Medical Center, Iowa City, IA, 52242, USA. matthew-potthoff@uiowa.edu
- Resource Type
- Journal article
- Publication Details
- Scientific reports, Vol.10(1), pp.19521-19521
- DOI
- 10.1038/s41598-020-76593-2
- PMID
- 33177640
- PMCID
- PMC7658965
- NLM abbreviation
- Sci Rep
- ISSN
- 2045-2322
- eISSN
- 2045-2322
- Publisher
- England
- Grant note
- T32 DK112751 / NIH HHS T32 DK112751 / NIDDK NIH HHS DK117510 / NIH HHS R01DK106104 / NIH HHS DK117515 / NIH HHS R01 AA027654 / NIAAA NIH HHS P30 DK054759 / NIDDK NIH HHS
- Language
- English
- Date published
- 11/11/2020
- Academic Unit
- Iowa Neuroscience Institute; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984070535402771
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