A lot of attention has been paid to mechanisms of thermogenesis, but much of this work has focused on the role of brown/beige adipose tissue. Muscle tissue is an extremely important organ for thermogenesis, as the major determinant of metabolic rate (Zurlo et al., 1990 and Nelson, et al. 1992). Understanding the mechanisms by which regulate adaptive thermogenesis is central to establishing negative energy balance to reduce obesity.
In Bal et al., 2012, the authors describe the role of sarcolipin in mediating this process. Sarcolipin is an ER localized protein, which can uncouple the SERCA ATP-dependent calcium channels (see Figure). This paper describes mice lacking the gene encoding sarcolipin (Sln) and describe how they are prone to excessive weight gain, likely due to lowered energy expenditure. By reducing the inefficient wasting of ATP due to futile cycling of calcium, these mice store more nutrients, rather than dissipating calories as heat.
In the few years since this paper was published Muthu Periasamy's group, now at Sanford-Burnham-Prebys Florida has continued this line of investigation, showing that muscle-specific overexpression of Sln has the inverse phenotype, with increased energy expenditure, and a resistance to diet-induced obesity (published in Maurya et al. 2015). This is an interesting contrast to studies on exercise performance, because they highlight the idea that inefficient muscle energy production is actually beneficial metabolically. Understanding ways by which sarcolipin and futile calcium cycling are regulated in vivo should be very important going forward.
A lot of attention has been paid to mechanisms of thermogenesis, but much of this work has focused on the role of brown/beige adipose tissue. Muscle tissue is an extremely important organ for thermogenesis, as the major determinant of metabolic rate (Zurlo et al., 1990 and Nelson, et al. 1992). Understanding the mechanisms by which regulate adaptive thermogenesis is central to establishing negative energy balance to reduce obesity.
In Bal et al., 2012, the authors describe the role of sarcolipin in mediating this process. Sarcolipin is an ER localized protein, which can uncouple the SERCA ATP-dependent calcium channels (see Figure). This paper describes mice lacking the gene encoding sarcolipin (Sln) and describe how they are prone to excessive weight gain, likely due to lowered energy expenditure. By reducing the inefficient wasting of ATP due to futile cycling of calcium, these mice store more nutrients, rather than dissipating calories as heat.
In the few years since this paper was published Muthu Periasamy's group, now at Sanford-Burnham-Prebys Florida has continued this line of investigation, showing that muscle-specific overexpression of Sln has the inverse phenotype, with increased energy expenditure, and a resistance to diet-induced obesity (published in Maurya et al. 2015). This is an interesting contrast to studies on exercise performance, because they highlight the idea that inefficient muscle energy production is actually beneficial metabolically. Understanding ways by which sarcolipin and futile calcium cycling are regulated in vivo should be very important going forward.
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