FGF21 signaling in glutamatergic neurons is required for weight loss associated with dietary protein dilution
Year: 2020
Type: article
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.
Source: Scientific Reports
Institutions: University of Iowa, Iowa City VA Medical Center
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $1,870
Awards: Endocrine Regulation of Alcohol Intake, G5175513010, G5191006302, G6531460157, Identification of a novel neural circuit regulating energy expenditure and glucose homeostasis, Fatty Acid Defects & Oxidative Stress Modulate Islet Function in Cystic Fibrosis, G8099488434, Novel Endocrine Circuit Regulating Sugar Satiety, Regulation of Metabolism by FGF21, Diabetes Research Training Program, Precision Medicine Center for Cystic Fibrosis
OpenAlex ID: W3098645453