Central serotonergic neurons activate and recruit thermogenic brown and beige fat and regulate glucose and lipid homeostasis

Jacob M McGlashon; Michelle C Gorecki; Amanda E Kozlowski; Caitlin K Thirnbeck; Kathleen R Markan; Kirstie L Leslie; Maya E Kotas; Matthew J Potthoff; George B Richerson; Matthew P Gillum

doi:10.1016/j.cmet.2015.04.008

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Central serotonergic neurons activate and recruit thermogenic brown and beige fat and regulate glucose and lipid homeostasis

Journal article

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Central serotonergic neurons activate and recruit thermogenic brown and beige fat and regulate glucose and lipid homeostasis

Jacob M McGlashon, Michelle C Gorecki, Amanda E Kozlowski, Caitlin K Thirnbeck, Kathleen R Markan, Kirstie L Leslie, Maya E Kotas, Matthew J Potthoff, George B Richerson and Matthew P Gillum

Cell metabolism, Vol.21(5), pp.692-705

05/05/2015

DOI: 10.1016/j.cmet.2015.04.008

PMCID: PMC4565052

PMID: 25955206

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Abstract

Thermogenic brown and beige adipocytes convert chemical energy to heat by metabolizing glucose and lipids. Serotonin (5-HT) neurons in the CNS are essential for thermoregulation and accordingly may control metabolic activity of thermogenic fat. To test this, we generated mice in which the human diphtheria toxin receptor (DTR) was selectively expressed in central 5-HT neurons. Treatment with diphtheria toxin (DT) eliminated 5-HT neurons and caused loss of thermoregulation, brown adipose tissue (BAT) steatosis, and a >50% decrease in uncoupling protein 1 (Ucp1) expression in BAT and inguinal white adipose tissue (WAT). In parallel, blood glucose increased 3.5-fold, free fatty acids 13.4-fold, and triglycerides 6.5-fold. Similar BAT and beige fat defects occurred in Lmx1b(f/f)ePet1(Cre) mice in which 5-HT neurons fail to develop in utero. We conclude 5-HT neurons play a major role in regulating glucose and lipid homeostasis, in part through recruitment and metabolic activation of brown and beige adipocytes.

Serotonergic Neurons - physiology

Body Temperature Regulation

Gene Expression Regulation

Adipose Tissue, Brown - physiology

Homeostasis

Ion Channels - genetics

Lipid Metabolism

Male

Mitochondrial Proteins - genetics

Adipose Tissue, White - innervation

Adipose Tissue, Brown - cytology

Adipose Tissue, Brown - innervation

Adipose Tissue, White - cytology

Animals

Thermogenesis

Adipose Tissue, White - physiology

Glucose - metabolism

Female

Mice

Uncoupling Protein 1

Details

Title: Subtitle: Central serotonergic neurons activate and recruit thermogenic brown and beige fat and regulate glucose and lipid homeostasis
Creators: Jacob M McGlashon - Department of Neurology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA; Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, 2200 Copenhagen, Denmark; Institute of Biomedical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark
Michelle C Gorecki - Department of Neurology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA; Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, 2200 Copenhagen, Denmark; Institute of Biomedical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark
Amanda E Kozlowski - Department of Neurology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA
Caitlin K Thirnbeck - Department of Neurology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA
Kathleen R Markan - Department of Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA
Kirstie L Leslie - Department of Neurology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA
Maya E Kotas - Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA
Matthew J Potthoff - Department of Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA
George B Richerson - Department of Neurology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA; Department of Molecular Physiology & Biophysics, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA; Veterans Affairs Medical Center, Iowa City, IA 52242, USA
Matthew P Gillum - Department of Neurology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA; Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, 2200 Copenhagen, Denmark; Institute of Biomedical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark. Electronic address: gillum@sund.ku.dk
Resource Type: Journal article
Publication Details: Cell metabolism, Vol.21(5), pp.692-705
Publisher: United States
DOI: 10.1016/j.cmet.2015.04.008
PMID: 25955206
PMCID: PMC4565052
ISSN: 1550-4131
eISSN: 1932-7420
Grant note: DK059637 / NIDDK NIH HHS R01 HL052539 / NHLBI NIH HHS DK020593 / NIDDK NIH HHS P30 DK020593 / NIDDK NIH HHS U24 DK059637 / NIDDK NIH HHS P60 DK020593 / NIDDK NIH HHS F32 DK102347 / NIDDK NIH HHS F32DK102347 / NIDDK NIH HHS U01 NS090414 / NINDS NIH HHS
Language: English
Date published: 05/05/2015
Academic Unit: Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute; Neuroscience and Pharmacology; Neurosurgery
Record Identifier: 9984020654802771

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