TY - JOUR
T1 - Loss of UCP2 impairs cold-induced non-shivering thermogenesis by promoting a shift toward glucose utilization in brown adipose tissue
AU - Caron, Alexandre
AU - Labbé, Sébastien M.
AU - Carter, Sophie
AU - Roy, Marie Claude
AU - Lecomte, Roger
AU - Ricquier, Daniel
AU - Picard, Frédéric
AU - Richard, Denis
N1 - Funding Information:
We are grateful to Jean-Fran?ois Beaudoin and Maxime Paill? for their helpful PET scan assistance and to Serge Phoenix and S?bastien Tremblay for radiotracers synthesis. DeR is supported by the Canadian Institutes of Health Research (CIHR: MOP-119436 and MOP-142361) and the Natural Sciences and Engineering Research Council of Canada (NSERC: 2014-06721). AC held a fellowship from the CIHR Training Program in Obesity/Healthy Body Weight and now holds a Canadian Diabetes Association post-doctoral fellowship. SML held a CIHR postdoctoral fellowship. SC held a Fonds de recherche du Qu?bec-Sant? (FRQ-S) fellowship.
Publisher Copyright:
© 2017 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM)
PY - 2017/3/1
Y1 - 2017/3/1
N2 - Uncoupling protein 2 (UCP2) was discovered in 1997 and classified as an uncoupling protein largely based on its homology of sequence with UCP1. Since its discovery, the uncoupling function of UCP2 has been questioned and there is yet no consensus on the true function of this protein. UCP2 was first proposed to be a reactive oxygen species (ROS) regulator and an insulin secretion modulator. More recently, it was demonstrated as a regulator of the mitochondrial fatty acid oxidation, which prompted us to investigate its role in the metabolic and thermogenic functions of brown adipose tissue. We first investigated the role of UCP2 in affecting the glycolysis capacity by evaluating the extracellular flux in cells lacking UCP2. We thereafter investigated the role of UCP2 in BAT thermogenesis with positron emission tomography using the metabolic tracers [11C]-acetate (metabolic activity), 2-deoxy-2-[18F]-fluoro-D-glucose (18FDG, glucose uptake) and 14(R,S)-[18F]fluoro-6-thia-heptadecanoic acid [18FTHA, non-esterified fatty acid (NEFA) uptake]. The effect of the β3-adrenoreceptor (ADRB3) selective agonist, CL316,243 (CL), on BAT 18FDG and 18FTHA uptakes, as well as 11C-acetate activity was assessed in UCP2KO and UCP2WT mice exposed at room temperature or adapted to cold. Our results suggest that despite the fact that UCP2 does not have the uncoupling potential of UCP1, its contribution to BAT thermogenesis and to the adaptation to cold exposure appears crucial. Notably, we found that the absence of UCP2 promoted a shift toward glucose utilization and increased glycolytic capacity in BAT, which conferred a better oxidative/thermogenic activity/capacity following an acute adrenergic stimulation. However, following cold exposure, a context of high-energy demand, BAT of UCP2KO mice failed to adapt and thermogenesis was impaired. We conclude that UCP2 regulates BAT thermogenesis by favouring the utilization of NEFA, a process required for the adaptation to cold.
AB - Uncoupling protein 2 (UCP2) was discovered in 1997 and classified as an uncoupling protein largely based on its homology of sequence with UCP1. Since its discovery, the uncoupling function of UCP2 has been questioned and there is yet no consensus on the true function of this protein. UCP2 was first proposed to be a reactive oxygen species (ROS) regulator and an insulin secretion modulator. More recently, it was demonstrated as a regulator of the mitochondrial fatty acid oxidation, which prompted us to investigate its role in the metabolic and thermogenic functions of brown adipose tissue. We first investigated the role of UCP2 in affecting the glycolysis capacity by evaluating the extracellular flux in cells lacking UCP2. We thereafter investigated the role of UCP2 in BAT thermogenesis with positron emission tomography using the metabolic tracers [11C]-acetate (metabolic activity), 2-deoxy-2-[18F]-fluoro-D-glucose (18FDG, glucose uptake) and 14(R,S)-[18F]fluoro-6-thia-heptadecanoic acid [18FTHA, non-esterified fatty acid (NEFA) uptake]. The effect of the β3-adrenoreceptor (ADRB3) selective agonist, CL316,243 (CL), on BAT 18FDG and 18FTHA uptakes, as well as 11C-acetate activity was assessed in UCP2KO and UCP2WT mice exposed at room temperature or adapted to cold. Our results suggest that despite the fact that UCP2 does not have the uncoupling potential of UCP1, its contribution to BAT thermogenesis and to the adaptation to cold exposure appears crucial. Notably, we found that the absence of UCP2 promoted a shift toward glucose utilization and increased glycolytic capacity in BAT, which conferred a better oxidative/thermogenic activity/capacity following an acute adrenergic stimulation. However, following cold exposure, a context of high-energy demand, BAT of UCP2KO mice failed to adapt and thermogenesis was impaired. We conclude that UCP2 regulates BAT thermogenesis by favouring the utilization of NEFA, a process required for the adaptation to cold.
KW - Brown adipose tissue
KW - Cold
KW - Energy metabolism
KW - FDG
KW - FTHA
KW - Position emission tomography
UR - http://www.scopus.com/inward/record.url?scp=85011066688&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85011066688&partnerID=8YFLogxK
U2 - 10.1016/j.biochi.2017.01.006
DO - 10.1016/j.biochi.2017.01.006
M3 - Article
C2 - 28130074
AN - SCOPUS:85011066688
SN - 0300-9084
VL - 134
SP - 118
EP - 126
JO - Biochimie
JF - Biochimie
ER -