Leslie A Rowland1, Santosh K Maurya2, Naresh C Bal1,2, Leslie Kozak3, Muthu Periasamy1,2. 1. Department of Physiology and Cell Biology, The Ohio State University, College of Medicine, Columbus, Ohio, USA. 2. Sanford Burnham Prebys Medical Discovery Institute, Lake Nona, Orlando, Florida, USA. 3. Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Olsztyn, Poland.
Abstract
OBJECTIVE: It is well known that uncoupling protein 1 (UCP1) in brown adipose tissue plays an important role in diet-induced thermogenesis. In this study, whether sarcolipin (SLN), a regulator of sarco/endoplasmic reticulum Ca(2+) -ATPase pump in muscle, is also an important player of diet-induced thermogenesis was investigated, as well as whether loss of SLN could be compensated by increased UCP1 expression and vice versa. METHODS: Age- and sex-matched UCP1(-/-) , SLN(-/-) , and double knockout for both UCP1 and SLN mice maintained in C57Bl/6J background were challenged to high-fat diet for 12 weeks and then analyzed for weight gain, alterations in serum metabolites, and changes in thermogenic protein expression. RESULTS: Loss of either SLN or UCP1 alone was sufficient to cause diet-induced obesity. No compensatory upregulation of UCP1 in SLN(-/-) mice or vice versa was found. Paradoxically, loss of both mechanisms failed to exacerbate the obesity phenotype. CONCLUSIONS: Data suggest that both SLN- and UCP1-based adaptive thermogenic mechanisms were essential for achieving maximal diet-induced thermogenesis. When both mechanisms were absent, less efficient thermogenic mechanisms were activated to counter energy imbalance.
OBJECTIVE: It is well known that uncoupling protein 1 (UCP1) in brown adipose tissue plays an important role in diet-induced thermogenesis. In this study, whether sarcolipin (SLN), a regulator of sarco/endoplasmic reticulum Ca(2+) -ATPase pump in muscle, is also an important player of diet-induced thermogenesis was investigated, as well as whether loss of SLN could be compensated by increased UCP1 expression and vice versa. METHODS: Age- and sex-matched UCP1(-/-) , SLN(-/-) , and double knockout for both UCP1 and SLNmice maintained in C57Bl/6J background were challenged to high-fat diet for 12 weeks and then analyzed for weight gain, alterations in serum metabolites, and changes in thermogenic protein expression. RESULTS: Loss of either SLN or UCP1 alone was sufficient to cause diet-induced obesity. No compensatory upregulation of UCP1 in SLN(-/-) mice or vice versa was found. Paradoxically, loss of both mechanisms failed to exacerbate the obesity phenotype. CONCLUSIONS: Data suggest that both SLN- and UCP1-based adaptive thermogenic mechanisms were essential for achieving maximal diet-induced thermogenesis. When both mechanisms were absent, less efficient thermogenic mechanisms were activated to counter energy imbalance.
Authors: Pengxiang She; Tanya M Reid; Sarah K Bronson; Thomas C Vary; Andras Hajnal; Christopher J Lynch; Susan M Hutson Journal: Cell Metab Date: 2007-09 Impact factor: 27.287
Authors: Eric S Bachman; Harveen Dhillon; Chen-Yu Zhang; Saverio Cinti; Antonio C Bianco; Brian K Kobilka; Bradford B Lowell Journal: Science Date: 2002-08-02 Impact factor: 47.728
Authors: Lawrence Kazak; Edward T Chouchani; Mark P Jedrychowski; Brian K Erickson; Kosaku Shinoda; Paul Cohen; Ramalingam Vetrivelan; Gina Z Lu; Dina Laznik-Bogoslavski; Sebastian C Hasenfuss; Shingo Kajimura; Steve P Gygi; Bruce M Spiegelman Journal: Cell Date: 2015-10-22 Impact factor: 41.582
Authors: Naresh C Bal; Santosh K Maurya; Danesh H Sopariwala; Sanjaya K Sahoo; Subash C Gupta; Sana A Shaikh; Meghna Pant; Leslie A Rowland; Eric Bombardier; Sanjeewa A Goonasekera; A Russell Tupling; Jeffery D Molkentin; Muthu Periasamy Journal: Nat Med Date: 2012-09-09 Impact factor: 53.440
Authors: Lawrence Kazak; Edward T Chouchani; Gina Z Lu; Mark P Jedrychowski; Curtis J Bare; Amir I Mina; Manju Kumari; Song Zhang; Ivan Vuckovic; Dina Laznik-Bogoslavski; Petras Dzeja; Alexander S Banks; Evan D Rosen; Bruce M Spiegelman Journal: Cell Metab Date: 2017-08-24 Impact factor: 27.287
Authors: David M Presby; L Allyson Checkley; Matthew R Jackman; Janine A Higgins; Kenneth L Jones; Erin D Giles; Julie A Houck; Patricia G Webb; Amy J Steig; Ginger C Johnson; Michael C Rudolph; Paul S MacLean Journal: Am J Physiol Regul Integr Comp Physiol Date: 2019-09-25 Impact factor: 3.619
Authors: Nathan C Winn; Victoria J Vieira-Potter; Michelle L Gastecki; Rebecca J Welly; Rebecca J Scroggins; Terese M Zidon; T'Keaya L Gaines; Makenzie L Woodford; Natalia G Karasseva; Jill A Kanaley; Harold S Sacks; Jaume Padilla Journal: Am J Physiol Regul Integr Comp Physiol Date: 2016-11-23 Impact factor: 3.619
Authors: Alexander W Fischer; Janina Behrens; Frederike Sass; Christian Schlein; Markus Heine; Paul Pertzborn; Ludger Scheja; Joerg Heeren Journal: J Lipid Res Date: 2020-08-07 Impact factor: 5.922
Authors: Su Myung Jung; Chien-Min Hung; Samuel R Hildebrand; Joan Sanchez-Gurmaches; Barbara Martinez-Pastor; Jivani M Gengatharan; Martina Wallace; Dimpi Mukhopadhyay; Camila Martinez Calejman; Amelia K Luciano; Wen-Yu Hsiao; Yuefeng Tang; Huawei Li; Danette L Daniels; Raul Mostoslavsky; Christian M Metallo; David A Guertin Journal: Mol Cell Date: 2019-08-22 Impact factor: 17.970
Authors: E Matthew Morris; Roberto D Noland; Julie A Allen; Colin S McCoin; Qing Xia; Devin C Koestler; Robin P Shook; John R B Lighton; Julie A Christianson; John P Thyfault Journal: Obesity (Silver Spring) Date: 2020-08-28 Impact factor: 9.298