Increased Reliance on Muscle-based Thermogenesis upon Acute Minimization of Brown Adipose Tissue Function.
Journal of Biological Chemistry 291(33):17247 (2016)
Skeletal muscle has been suggested as a site of nonshivering thermogenesis (NST) besides brown adipose tissue (BAT). Studies in birds, which do not contain BAT, have demonstrated the importance of skeletal muscle-based NST. However, muscle-based NST in mammals remains poorly characterized. We re...
Sarcolipin and uncoupling protein 1 play distinct roles in diet-induced thermogenesis and do not compensate for one another.
Obesity 24(7):1430 (2016)
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 thermoge...
Phospholamban and sarcolipin: Are they functionally redundant or distinct regulators of the Sarco(Endo)Plasmic Reticulum Calcium ATPase?
Journal of Molecular and Cellular Cardiology 91:81 (2016)
In muscle, the Sarco(Endo)plasmic Reticulum Calcium ATPase (SERCA) activity is regulated by two distinct proteins, PLB and SLN, which are highly conserved throughout vertebrate evolution. PLB is predominantly expressed in the cardiac muscle, while SLN is abundant in skeletal muscle. SLN is also ...
miR-155 Deletion in Female Mice Prevents Diet-Induced Obesity.
Scientific reports 6:22862 (2016)
Obesity is a growing epidemic in developed countries. Obese individuals are susceptible to comorbidities, including cardiovascular disease and metabolic disorder. Increasing the ability of adipose tissue to expend excess energy could improve protection from obesity. One promising target is micro...
Graded Maximal Exercise Testing to Assess Mouse Cardio-Metabolic Phenotypes.
PLoS ONE 11(2):e0148010 (2016)
Functional assessments of cardiovascular fitness (CVF) are needed to establish animal models of dysfunction, test the effects of novel therapeutics, and establish the cardio-metabolic phenotype of mice. In humans, the graded maximal exercise test (GXT) is a standardized diagnostic for assessing ...
Sarcolipin is a novel regulator of muscle metabolism and obesity.
Pharmacological Research 102:270 (2015)
Obesity is increasing at an alarming rate, both in adults and adolescents, across the globe due to increased consumption of caloric rich diet. Obesity and its associated complications appear to be major contributing factors not only to diabetes/heart disease but also to cancer, and neurological ...
The role of skeletal-muscle-based thermogenic mechanisms in vertebrate endothermy.
Biological Reviews of the Cambridge Philosophic... 90(4):1279 (2015)
Thermogenesis is one of the most important homeostatic mechanisms that evolved during vertebrate evolution. Despite its importance for the survival of the organism, the mechanistic details behind various thermogenic processes remain incompletely understood. Although heat production from muscle h...
Cold adaptation overrides developmental regulation of sarcolipin expression in mice skeletal muscle: SOS for muscle-based thermogenesis?
Journal of Experimental Biology 218(Pt 15):2321 (2015)
Neonatal mice have a greater thermogenic need than adult mice and may require additional means of heat production, other than the established mechanism of brown adipose tissue (BAT). We and others recently discovered a novel mediator of skeletal muscle-based thermogenesis called sarcolipin (SLN)...
The N Terminus of Sarcolipin Plays an Important Role in Uncoupling Sarco-endoplasmic Reticulum Ca2+-ATPase (SERCA) ATP Hydrolysis from Ca2+ Transport.
Journal of Biological Chemistry 290(22):14057 (2015)
The sarcoendoplasmic reticulum Ca(2+)-ATPase (SERCA) is responsible for intracellular Ca(2+) homeostasis. SERCA activity in muscle can be regulated by phospholamban (PLB), an affinity modulator, and sarcolipin (SLN), an uncoupler. Although PLB gets dislodged from Ca(2+)-bound SERCA, SLN continue...
Uncoupling Protein 1 and Sarcolipin Are Required to Maintain Optimal Thermogenesis, and Loss of Both Systems Compromises Survival of Mice under Cold Stress.
Journal of Biological Chemistry 290(19):12282 (2015)
The importance of brown adipose tissue as a site of nonshivering thermogenesis has been well documented. Emerging studies suggest that skeletal muscle is also an important site of thermogenesis especially when brown adipose tissue function is lacking. We recently showed that sarcolipin (SLN), an...
Sarcoplasmic reticulum Ca2+ ATPase pump is a major regulator of glucose transport in the healthy and diabetic heart.
Biochimica et Biophysica Acta 1852(5):873 (2015)
Despite intensive research, the pathways that mediate calcium (Ca(2+))-stimulated glucose transport in striated muscle remain elusive. Since the sarcoplasmic reticulum calcium ATPase (SERCA) pump tightly regulates cytosolic [Ca(2+)], we investigated whether the SERCA pump is a major regulator of...
Sarcolipin Is a Key Determinant of the Basal Metabolic Rate, and Its Overexpression Enhances Energy Expenditure and Resistance against Diet-induced Obesity.
Journal of Biological Chemistry 290(17):10840 (2015)
Sarcolipin (SLN) is a novel regulator of sarcoplasmic reticulum Ca(2+) ATPase (SERCA) in muscle. SLN binding to SERCA uncouples Ca(2+) transport from ATP hydrolysis. By this mechanism, SLN promotes the futile cycling of SERCA, contributing to muscle heat production. We recently showed that SLN p...
Sarcolipin overexpression improves muscle energetics and reduces fatigue.
Journal of Applied Physiology 118(8):1050 (2015)
Sarcolipin (SLN) is a regulator of sarcoendoplasmic reticulum calcium ATPase in skeletal muscle. Recent studies using SLN-null mice have identified SLN as a key player in muscle thermogenesis and metabolism. In this study, we exploited a SLN overexpression (Sln(OE)) mouse model to determine whet...
Obligatory role of neuronal nitric oxide synthase in the heart's antioxidant adaptation with exercise.
Journal of Molecular and Cellular Cardiology 81:54 (2015)
Excessive oxidative stress in the heart results in contractile dysfunction. While antioxidant therapies have been a disappointment clinically, exercise has shown beneficial results, in part by reducing oxidative stress. We have previously shown that neuronal nitric oxide synthase (nNOS) is essen...
Calsequestrin 2 deletion causes sinoatrial node dysfunction and atrial arrhythmias associated with altered sarcoplasmic reticulum calcium cycling and degenerative fibrosis within the mouse atrial pacemaker complex1.
European Heart Journal 36(11):686 (2015)
Loss-of-function mutations in Calsequestrin 2 (CASQ2) are associated with catecholaminergic polymorphic ventricular tachycardia (CPVT). CPVT patients also exhibit bradycardia and atrial arrhythmias for which the underlying mechanism remains unknown. We aimed to study the sinoatrial node (SAN) dy...
Metabolic dysfunction and altered mitochondrial dynamics in the utrophin-dystrophin deficient mouse model of duchenne muscular dystrophy.
PLoS ONE 10(4):e0123875 (2015)
The utrophin-dystrophin deficient (DKO) mouse model has been widely used to understand the progression of Duchenne muscular dystrophy (DMD). However, it is unclear as to what extent muscle pathology affects metabolism. Therefore, the present study was focused on understanding energy expenditure ...
The C-terminal calcium-sensitive disordered motifs regulate isoform-specific polymerization characteristics of calsequestrin.
Biopolymers 103(1):15 (2015)
Calsequestrin (CASQ) exists as two distinct isoforms CASQ1 and CASQ2 in all vertebrates. Although the isoforms exhibit unique functional characteristic, the structural basis for the same is yet to be fully defined. Interestingly, the C-terminal region of the two isoforms exhibit significant diff...
Acute dim light at night increases body mass, alters metabolism, and shifts core body temperature circadian rhythms.
Chronobiology International 31(8):917 (2014)
The circadian system is primarily entrained by the ambient light environment and is fundamentally linked to metabolism. Mounting evidence suggests a causal relationship among aberrant light exposure, shift work, and metabolic disease. Previous research has demonstrated deleterious metabolic phen...
Effects of insulin resistance on skeletal muscle growth and exercise capacity in type 2 diabetic mouse models.
American Journal of Physiology - Endocrinology ... 306(6):E592 (2014)
Type 2 diabetes mellitus is associated with an accelerated muscle loss during aging, decreased muscle function, and increased disability. To better understand the mechanisms causing this muscle deterioration in type 2 diabetes, we assessed muscle weight, exercise capacity, and biochemistry in db...
Sarcolipin Regulation of SERCA is Distinct from Phospholamban
Biophysical Journal 106(2):584a (2014)