| Autor: |
Flippo KH; Department of Neuroscience and Pharmacology, University of Iowa Carver College of Medicine, 169 Newton Road, 3322 PBDB, 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., Jensen-Cody SO; Department of Neuroscience and Pharmacology, University of Iowa Carver College of Medicine, 169 Newton Road, 3322 PBDB, 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., Claflin KE; Department of Neuroscience and Pharmacology, University of Iowa Carver College of Medicine, 169 Newton Road, 3322 PBDB, 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., Potthoff MJ; Department of Neuroscience and Pharmacology, University of Iowa Carver College of Medicine, 169 Newton Road, 3322 PBDB, Iowa City, IA, 52242, USA. matthew-potthoff@uiowa.edu.; Fraternal Order of Eagles Diabetes Research Center, University of Iowa Carver College of Medicine, Iowa City, IA, 52242, USA. matthew-potthoff@uiowa.edu.; Iowa Neuroscience Institute, University of Iowa Carver College of Medicine, Iowa City, IA, 52242, USA. matthew-potthoff@uiowa.edu.; Department of Veterans Affairs Medical Center, Iowa City, IA, 52242, USA. matthew-potthoff@uiowa.edu. |
| Abstrakt: |
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. |
