Brown adipose tissue lipoprotein and glucose disposal is not determined by thermogenesis in uncoupling protein 1-deficient mice
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
Brown adipose tissue lipoprotein and glucose disposal is not determined by thermogenesis in uncoupling protein 1-deficient mice. / Fischer, Alexander W.; Behrens, Janina; Sass, Frederike; Schlein, Christian; Heine, Markus; Pertzborn, Paul; Scheja, Ludger; Heeren, Joerg.
In: Journal of Lipid Research, Vol. 61, No. 11, 2020, p. 1377-1389.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Brown adipose tissue lipoprotein and glucose disposal is not determined by thermogenesis in uncoupling protein 1-deficient mice
AU - Fischer, Alexander W.
AU - Behrens, Janina
AU - Sass, Frederike
AU - Schlein, Christian
AU - Heine, Markus
AU - Pertzborn, Paul
AU - Scheja, Ludger
AU - Heeren, Joerg
PY - 2020
Y1 - 2020
N2 - Adaptive thermogenesis is highly dependent on uncoupling protein 1 (UCP1), a protein expressed by thermogenic adipocytes present in brown adipose tissue (BAT) and white adipose tissue (WAT). Thermogenic capacity of human and mouse BAT can be measured by positron emission tomography-computed tomography quantifying the uptake of F-18-fluodeoxyglucose or lipid tracers. BAT activation is typically studied in response to cold exposure or treatment with beta-3-adrenergic receptor agonists such as CL316,243 (CL). Currently, it is unknown whether cold-stimulated uptake of glucose or lipid tracers is a good surrogate marker of UCP1-mediated thermogenesis. In metabolic studies using radiolabeled tracers, we found that glucose uptake is increased in mildly cold-activated BAT of Ucp1(-/-) versus WT mice kept at subthermoneutral temperature. Conversely, lower glucose disposal was detected after full thermogenic activation achieved by sustained cold exposure or CL treatment. In contrast, uptake of lipoprotein-derived fatty acids into chronically activated thermogenic adipose tissues was substantially increased in UCP1-deficient mice. This effect is linked to higher sympathetic tone in adipose tissues of Ucp1(-/-) mice, as indicated by elevated levels of thermogenic genes in BAT and WAT. Thus, glucose and lipoprotein handling does not necessarily reflect UCP1-dependent thermogenic activity, but especially lipid uptake rather mirrors sympathetic activation of adipose tissues.
AB - Adaptive thermogenesis is highly dependent on uncoupling protein 1 (UCP1), a protein expressed by thermogenic adipocytes present in brown adipose tissue (BAT) and white adipose tissue (WAT). Thermogenic capacity of human and mouse BAT can be measured by positron emission tomography-computed tomography quantifying the uptake of F-18-fluodeoxyglucose or lipid tracers. BAT activation is typically studied in response to cold exposure or treatment with beta-3-adrenergic receptor agonists such as CL316,243 (CL). Currently, it is unknown whether cold-stimulated uptake of glucose or lipid tracers is a good surrogate marker of UCP1-mediated thermogenesis. In metabolic studies using radiolabeled tracers, we found that glucose uptake is increased in mildly cold-activated BAT of Ucp1(-/-) versus WT mice kept at subthermoneutral temperature. Conversely, lower glucose disposal was detected after full thermogenic activation achieved by sustained cold exposure or CL treatment. In contrast, uptake of lipoprotein-derived fatty acids into chronically activated thermogenic adipose tissues was substantially increased in UCP1-deficient mice. This effect is linked to higher sympathetic tone in adipose tissues of Ucp1(-/-) mice, as indicated by elevated levels of thermogenic genes in BAT and WAT. Thus, glucose and lipoprotein handling does not necessarily reflect UCP1-dependent thermogenic activity, but especially lipid uptake rather mirrors sympathetic activation of adipose tissues.
KW - adipocytes
KW - lipase
KW - lipoprotein
KW - lipid metabolism
KW - hormone-sensitive
KW - lipid transport
KW - lipolysis and fatty acid metabolism
KW - lipoprotein metabolism
KW - triglycerides
KW - MUSCLE-BASED THERMOGENESIS
KW - DIET-INDUCED THERMOGENESIS
KW - FATTY-ACID TRANSPORT
KW - ENERGY-EXPENDITURE
KW - NONSHIVERING THERMOGENESIS
KW - OXIDATIVE-METABOLISM
KW - COLD-EXPOSURE
KW - UCP1
KW - WHITE
KW - FGF21
U2 - 10.1194/jlr.RA119000455
DO - 10.1194/jlr.RA119000455
M3 - Journal article
C2 - 32769145
VL - 61
SP - 1377
EP - 1389
JO - Journal of Lipid Research
JF - Journal of Lipid Research
SN - 0022-2275
IS - 11
ER -
ID: 251945394