Sarcolipin and uncoupling protein 1 play distinct roles in diet-induced thermogenesis and do not compensate for one another

Obesity (Silver Spring). 2016 Jul;24(7):1430-3. doi: 10.1002/oby.21542. Epub 2016 May 30.


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.

MeSH terms

  • Adipose Tissue, Brown / metabolism
  • Animals
  • Diet*
  • Diet, High-Fat
  • Energy Metabolism
  • Ion Channels / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mitochondrial Proteins / genetics
  • Muscle Proteins / deficiency
  • Muscle Proteins / physiology*
  • Obesity / metabolism
  • Obesity / physiopathology
  • Proteolipids / deficiency
  • Proteolipids / physiology*
  • Thermogenesis / physiology*
  • Uncoupling Protein 1 / deficiency
  • Uncoupling Protein 1 / physiology*
  • Weight Gain


  • Ion Channels
  • Mitochondrial Proteins
  • Muscle Proteins
  • Proteolipids
  • Uncoupling Protein 1
  • sarcolipin