TY - JOUR
T1 - Central Serotonergic Neurons Activate and Recruit Thermogenic Brown and Beige Fat and Regulate Glucose and Lipid Homeostasis
AU - McGlashon, Jacob M.
AU - Gorecki, Michelle C.
AU - Kozlowski, Amanda E.
AU - Thirnbeck, Caitlin K.
AU - Markan, Kathleen R.
AU - Leslie, Kirstie L.
AU - Kotas, Maya E.
AU - Potthoff, Matthew J.
AU - Richerson, George B.
AU - Gillum, Matthew P.
N1 - Publisher Copyright:
© 2015 Elsevier Inc.
PY - 2015/5/1
Y1 - 2015/5/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84984804817&partnerID=8YFLogxK
U2 - 10.1016/j.cmet.2015.04.008
DO - 10.1016/j.cmet.2015.04.008
M3 - Article
C2 - 25955206
AN - SCOPUS:84984804817
SN - 1550-4131
VL - 21
SP - 692
EP - 705
JO - Cell metabolism
JF - Cell metabolism
IS - 5
ER -