Brown adipose tissue lipoprotein and glucose disposal is not determined by thermogenesis in uncoupling protein 1-deficient mice

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • Alexander W. Fischer
  • Janina Behrens
  • Sass, Frederike
  • Christian Schlein
  • Markus Heine
  • Paul Pertzborn
  • Ludger Scheja
  • Joerg Heeren

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.

TidsskriftJournal of Lipid Research
Udgave nummer11
Sider (fra-til)1377-1389
Antal sider13
StatusUdgivet - 2020
Eksternt udgivetJa

ID: 251945394