PPARγ in vagal neurons regulates high-fat diet induced thermogenesis.
The vagus nerve innervates visceral organs providing a link between key metabolic cues and the CNS. However, it is not clear whether vagal neurons can directly respond to changing lipid levels and whether altered "lipid sensing" by the vagus nerve regulates energy balance. In this study, we systematically profiled the expression of all known nuclear receptors in laser-captured nodose ganglion (NG) neurons. In particular, we found PPARγ expression was reduced by high-fat-diet feeding. Deletion of PPARγ in Phox2b neurons promoted HFD-induced thermogenesis that involved the reprograming of white adipocyte into a brown-like adipocyte cell fate. Finally, we showed that PPARγ in NG neurons regulates genes necessary for lipid metabolism and those that are important for synaptic transmission. Collectively, our findings provide insights into how vagal afferents survey peripheral metabolic cues and suggest that the reduction of PPARγ in NG neurons may serve as a protective mechanism against diet-induced weight gain.
Division of Hypothalamic Research, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
Chen
C
Liu
Division of Hypothalamic Research, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA; Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
Angie L
AL
Bookout
Division of Hypothalamic Research, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
Syann
S
Lee
Touchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
Kai
K
Sun
Division of Hypothalamic Research, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
Lin
L
Jia
Division of Hypothalamic Research, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
Charlotte
C
Lee
Division of Hypothalamic Research, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
Swalpa
S
Udit
Touchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
Yingfeng
Y
Deng
Touchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
Philipp E
PE
Scherer
Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
David J
DJ
Mangelsdorf
Division of Hypothalamic Research, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA. Electronic address: laurent.gautron@utsouthwestern.edu.
Laurent
L
Gautron
Division of Hypothalamic Research, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA; Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA. Electronic address: joel.elmquist@utsouthwestern.edu.
Joel K
JK
Elmquist
D017667:Adipocytes / Q000166:cytology; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D059305:Diet, High-Fat; D017353:Gene Deletion; D005786:Gene Expression Regulation / Q000502:physiology; D061346:Laser Capture Microdissection; D050356:Lipid Metabolism / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D009474:Neurons / Q000378:metabolism* / Q000502:physiology; D009620:Nodose Ganglion / Q000166:cytology* / Q000601:surgery; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D022722:Thermogenesis / Q000502:physiology*
D047495:PPAR gamma