Sarcolipin is a Newly Identified Regulator of Muscle-based Thermogenesis in Mammals

Overview

Journal Nat Med

Specialties General Medicine
Molecular Biology

Date 2012 Sep 11

PMID 22961106

Citations 275

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

Affiliations

Soon will be listed here.

Abstract

The role of skeletal muscle in nonshivering thermogenesis (NST) is not well understood. Here we show that sarcolipin (Sln), a newly identified regulator of the sarco/endoplasmic reticulum Ca(2+)-ATPase (Serca) pump, is necessary for muscle-based thermogenesis. When challenged to acute cold (4 °C), Sln(-/-) mice were not able to maintain their core body temperature (37 °C) and developed hypothermia. Surgical ablation of brown adipose tissue and functional knockdown of Ucp1 allowed us to highlight the role of muscle in NST. Overexpression of Sln in the Sln-null background fully restored muscle-based thermogenesis, suggesting that Sln is the basis for Serca-mediated heat production. We show that ryanodine receptor 1 (Ryr1)-mediated Ca(2+) leak is an important mechanism for Serca-activated heat generation. Here we present data to suggest that Sln can continue to interact with Serca in the presence of Ca(2+), which can promote uncoupling of the Serca pump and cause futile cycling. We further show that loss of Sln predisposes mice to diet-induced obesity, which suggests that Sln-mediated NST is recruited during metabolic overload. These data collectively suggest that SLN is an important mediator of muscle thermogenesis and whole-body energy metabolism.

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