Periasamy 2017 MiP2017

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Targeting skeletal muscle energetics to control obesity and diabetes.

Link: MiP2017

Periasamy M (2017)

Event: MiP2017

COST Action MITOEAGLE
Obesity is taking the form of a pandemic and is increasing at an alarming rate throughout the globe. Obesity is a major contributing factor for Type 2 diabetes and cardiovascular diseases' increasing health care cost. Skeletal muscle constitutes ~40% of body mass and is a major consumer of metabolites, including glucose and fat. Increasing fuel utilization in muscle is an effective strategy to control obesity and Type 2 diabetes. Our research focuses on the role of sarcoplasmic reticulum (SR) Ca2+ cycling (ATP dependent) and its impact on mitochondrial energetics. We have identified a muscle protein, namely sarcolipin (SLN), that uncouples the SERCA pump from Ca2+ transport but increases ATP hydrolysis and heat production. By promoting futile cycling of SERCA pump; SLN regulates muscle thermogenesis and metabolism as shown in genetically altered mouse models of SLN. We reported that mice lacking SLN protein were poor in metabolizing fat and became obese, whereas mice overexpressing SLN in skeletal muscle were resistant to high-fat diet-induced obesity [1,2]. An important finding was that SLN overexpression in glycolytic muscle led to an increase in mitochondrial biogenesis and oxidative metabolism as assessed by the Oroboros system. In addition mice overexpressing SLN performed better during endurance running test, ran longer and were less fatigued compared to control mice. These mice also showed better functional recovery after prolonged running. Our data suggests that SLN is important for metabolic flexibility especially for increased fat oxidation during high-energy demand states. Our long-term goal is to develop novel therapies to control obesity by increasing energy expenditure in muscle.


Bioblast editor: Kandolf G O2k-Network Lab: US FL Orlando Periasamy M


Labels: MiParea: Respiration, mt-Biogenesis;mt-density, Exercise physiology;nutrition;life style  Pathology: Diabetes, Obesity 

Organism: Mouse 




HRR: Oxygraph-2k 


Affiliations

Sanford Burnham Prebys Medical Discovery Inst, Orlando, FL, USA. - mperiasamy@sbpdiscovery.org

References

  1. Bal NC, Maurya SK, Sopariwala DH, Sahoo SK, Gupta SC, Shaikh SA, Pant M, Rowland LA, Bombardier E, Goonasekera SA, Tupling AR, Molkentin JD, Periasamy M (2012) Sarcolipin is a newly identified regulator of muscle-based thermogenesis in mammals. Nature Medicine 18:1575-79.
  2. Maurya SK, Bal NC, Sopariwala DH, Pant M, Rowland LA, Shaikh SA, Periasamy M (2015) Sarcolipin is a key determinant of the basal metabolic rate, and its overexpression enhances energy expenditure and resistance against diet-induced obesity. J Biol Chem 290:10840-49.