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Low-dose lithium supplementation promotes adipose tissue browning and sarco(endo)plasmic reticulum Ca2+ ATPase uncoupling in muscle.
Geromella, Mia S; Ryan, Chantal R; Braun, Jessica L; Finch, Michael S; Maddalena, Lucas A; Bagshaw, Olivia; Hockey, Briana L; Moradi, Fereshteh; Fenech, Rachel K; Ryoo, Jisook; Marko, Daniel M; Dhaliwal, Roopan; Sweezey-Munroe, Jake; Hamstra, Sophie I; Gardner, Georgina; Silvera, Sebastian; Vandenboom, Rene; Roy, Brian D; Stuart, Jeffrey A; MacPherson, Rebecca E K; Fajardo, Val A.
Afiliación
  • Geromella MS; Department of Kinesiology, Brock University, St. Catharines, Ontario, Canada; Centre for Bone and Muscle Health, Brock University, St. Catharines, Ontario, Canada.
  • Ryan CR; Department of Health Sciences, Brock University, St. Catharines, Ontario, Canada.
  • Braun JL; Department of Kinesiology, Brock University, St. Catharines, Ontario, Canada; Centre for Bone and Muscle Health, Brock University, St. Catharines, Ontario, Canada.
  • Finch MS; Department of Health Sciences, Brock University, St. Catharines, Ontario, Canada.
  • Maddalena LA; Department of Biological Sciences, Brock University, St. Catharines, Ontario, Canada.
  • Bagshaw O; Department of Biological Sciences, Brock University, St. Catharines, Ontario, Canada.
  • Hockey BL; Department of Kinesiology, Brock University, St. Catharines, Ontario, Canada; Centre for Bone and Muscle Health, Brock University, St. Catharines, Ontario, Canada.
  • Moradi F; Department of Biological Sciences, Brock University, St. Catharines, Ontario, Canada.
  • Fenech RK; Department of Health Sciences, Brock University, St. Catharines, Ontario, Canada.
  • Ryoo J; Department of Kinesiology, Brock University, St. Catharines, Ontario, Canada; Centre for Bone and Muscle Health, Brock University, St. Catharines, Ontario, Canada.
  • Marko DM; Department of Health Sciences, Brock University, St. Catharines, Ontario, Canada.
  • Dhaliwal R; Department of Health Sciences, Brock University, St. Catharines, Ontario, Canada.
  • Sweezey-Munroe J; Department of Health Sciences, Brock University, St. Catharines, Ontario, Canada.
  • Hamstra SI; Department of Kinesiology, Brock University, St. Catharines, Ontario, Canada; Centre for Bone and Muscle Health, Brock University, St. Catharines, Ontario, Canada.
  • Gardner G; Department of Biological Sciences, Brock University, St. Catharines, Ontario, Canada.
  • Silvera S; Department of Kinesiology, Brock University, St. Catharines, Ontario, Canada; Centre for Bone and Muscle Health, Brock University, St. Catharines, Ontario, Canada.
  • Vandenboom R; Department of Kinesiology, Brock University, St. Catharines, Ontario, Canada; Centre for Bone and Muscle Health, Brock University, St. Catharines, Ontario, Canada.
  • Roy BD; Department of Kinesiology, Brock University, St. Catharines, Ontario, Canada; Centre for Bone and Muscle Health, Brock University, St. Catharines, Ontario, Canada.
  • Stuart JA; Department of Biological Sciences, Brock University, St. Catharines, Ontario, Canada.
  • MacPherson REK; Department of Health Sciences, Brock University, St. Catharines, Ontario, Canada. Electronic address: rmacpherson@brocku.ca.
  • Fajardo VA; Department of Kinesiology, Brock University, St. Catharines, Ontario, Canada; Centre for Bone and Muscle Health, Brock University, St. Catharines, Ontario, Canada. Electronic address: vfajardo@brocku.ca.
J Biol Chem ; 298(11): 102568, 2022 11.
Article en En | MEDLINE | ID: mdl-36209826
Sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) uncoupling in skeletal muscle and mitochondrial uncoupling via uncoupling protein 1 (UCP1) in brown/beige adipose tissue are two mechanisms implicated in energy expenditure. Here, we investigated the effects of glycogen synthase kinase 3 (GSK3) inhibition via lithium chloride (LiCl) treatment on SERCA uncoupling in skeletal muscle and UCP1 expression in adipose. C2C12 and 3T3-L1 cells treated with LiCl had increased SERCA uncoupling and UCP1 protein levels, respectively, ultimately raising cellular respiration; however, this was only observed when LiCl treatment occurred throughout differentiation. In vivo, LiCl treatment (10 mg/kg/day) increased food intake in chow-fed diet and high-fat diet (HFD; 60% kcal)-fed male mice without increasing body mass-a result attributed to elevated daily energy expenditure. In soleus muscle, we determined that LiCl treatment promoted SERCA uncoupling via increased expression of SERCA uncouplers, sarcolipin and/or neuronatin, under chow-fed and HFD-fed conditions. We attribute these effects to the GSK3 inhibition observed with LiCl treatment as partial muscle-specific GSK3 knockdown produced similar effects. In adipose, LiCl treatment inhibited GSK3 in inguinal white adipose tissue (iWAT) but not in brown adipose tissue under chow-fed conditions, which led to an increase in UCP1 in iWAT and a beiging-like effect with a multilocular phenotype. We did not observe this beiging-like effect and increase in UCP1 in mice fed a HFD, as LiCl could not overcome the ensuing overactivation of GSK3. Nonetheless, our study establishes novel regulatory links between GSK3 and SERCA uncoupling in muscle and GSK3 and UCP1 and beiging in iWAT.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Adenosina Trifosfatasas / Litio Límite: Animals Idioma: En Revista: J Biol Chem Año: 2022 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Adenosina Trifosfatasas / Litio Límite: Animals Idioma: En Revista: J Biol Chem Año: 2022 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Estados Unidos