Central Serotonergic Neurons Activate and Recruit Thermogenic Brown and Beige Fat and Regulate Glucose and Lipid Homeostasis

• Published in: Cell metabolism Vol. 21; no. 5; pp. 692 - 705
• Main Authors: McGlashon, Jacob M., Gorecki, Michelle C., Kozlowski, Amanda E., Thirnbeck, Caitlin K., Markan, Kathleen R., Leslie, Kirstie L., Kotas, Maya E., Potthoff, Matthew J., Richerson, George B., Gillum, Matthew P.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 05-05-2015
• Subjects: Adipose Tissue, Brown - cytology; Adipose Tissue, Brown - innervation; Adipose Tissue, Brown - physiology; Adipose Tissue, White - cytology; Adipose Tissue, White - innervation; Adipose Tissue, White - physiology; Animals; Body Temperature Regulation; Female; Gene Expression Regulation; Glucose - metabolism; Homeostasis; Ion Channels - genetics; Lipid Metabolism; Male; Mice; Mitochondrial Proteins - genetics; Serotonergic Neurons - physiology; Thermogenesis; Uncoupling Protein 1
• ISSN: 1550-4131; 1932-7420
• DOI: 10.1016/j.cmet.2015.04.008

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 Lmx1bf/fePet1Cre 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.
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•Pet-1 neurons control BAT activity, body temperature, and thermogenic gene expression•Pet-1 neurons regulate fat content and facilitate recruitment of beige fat from WAT•Pet-1 neurons are required to maintain normal blood glucose and lipid levels
McGlashon et al. show that brain serotonin (Pet-1+) neurons are necessary for sympathetic activation of adult mouse brown and beige/brite adipose tissue, as well as for the maintenance of the “brown” adipose phenotype and thermogenic BAT functionality, and normal blood glucose and lipid levels.