Skeletal muscle action of estrogen receptor α is critical for the maintenance of mitochondrial function and metabolic homeostasis in females.
Science Translational Medicine 8(334):334ra54 (2016)
Impaired estrogen receptor α (ERα) action promotes obesity and metabolic dysfunction in humans and mice; however, the mechanisms underlying these phenotypes remain unknown. Considering that skeletal muscle is a primary tissue responsible for glucose disposal and oxidative metabolism, we establis...
p300 is not required for metabolic adaptation to endurance exercise training.
FASEB Journal 30(4):1623 (2016)
The acetyltransferase, E1a-binding protein (p300), is proposed to regulate various aspects of skeletal muscle development, metabolism, and mitochondrial function,viaits interaction with numerous transcriptional regulators and other proteins. Remarkably, however, the contribution of p300 to skele...
Perm1 enhances mitochondrial biogenesis, oxidative capacity, and fatigue resistance in adult skeletal muscle.
FASEB Journal 30(2):674 (2016)
Skeletal muscle mitochondrial content and oxidative capacity are important determinants of muscle function and whole-body health. Mitochondrial content and function are enhanced by endurance exercise and impaired in states or diseases where muscle function is compromised, such as myopathies, mus...
Rapamycin does not prevent increases in myofibrillar or mitochondrial protein synthesis following endurance exercise.
Journal of Physiology 593(18):4275 (2015)
The present study aimed to investigate the role of the mechanistic target of rapamycin complex 1 (mTORC1) in the regulation of myofibrillar (MyoPS) and mitochondrial (MitoPS) protein synthesis following endurance exercise. Forty-two female C57BL/6 mice performed 1 h of treadmill running (18 m mi...
Knockout of STAT3 in skeletal muscle does not prevent high-fat diet-induced insulin resistance.
Molecular Metabolism 4(8):569 (2015)
Increased signal transducer and activator of transcription 3 (STAT3) signaling has been implicated in the development of skeletal muscle insulin resistance, though its contribution, in vivo, remains to be fully defined. Therefore, the aim of this study was to determine whether knockout of skelet...
Is acetylation a metabolic rheostat that regulates skeletal muscle insulin action?
Molecules and Cells 38(4):297 (2015)
Skeletal muscle insulin resistance, which increases the risk for developing various metabolic diseases, including type 2 diabetes, is a common metabolic disorder in obesity and aging. If potential treatments are to be developed to treat insulin resistance, then it is important to fully understan...
High-fat diet-induced impairment of skeletal muscle insulin sensitivity is not prevented by SIRT1 overexpression.
American Journal of Physiology - Endocrinology ... 307(9):E764 (2014)
Skeletal muscle sirtuin 1 (SIRT1) expression is reduced under insulin-resistant conditions, such as those resulting from high-fat diet (HFD) feeding and obesity. Herein, we investigated whether constitutive activation of SIRT1 in skeletal muscle prevents HFD-induced muscle insulin resistance. To...
Understanding the acetylome: translating targeted proteomics into meaningful physiology.
American Journal of Physiology - Cell Physiology 307(9):C763 (2014)
It is well established that exercise elicits a finely tuned adaptive response in skeletal muscle, with contraction frequency, duration, and recovery shaping skeletal muscle plasticity. Given the power of physical activity to regulate metabolic health, numerous research groups have focused on the...
Muscle gene expression patterns in human rotator cuff pathology.
Journal of Bone and Joint Surgery (American) 96(18):1558 (2014)
Rotator cuff pathology is a common source of shoulder pain with variable etiology and pathoanatomical characteristics. Pathological processes of fatty infiltration, muscle atrophy, and fibrosis have all been invoked as causes for poor outcomes after rotator cuff tear repair. The aims of this stu...
Muscle Gene Expression Patterns in Human Rotator Cuff Pathology
Journal of Bone and Joint Surgery (American) 96(18):1558 (2014)
Rotator cuff pathology is a common source of shoulder pain with variable etiology and pathoanatomical characteristics. Pathological processes of fatty infiltration, muscle atrophy, and fibrosis have all been invoked as causes for poor outcomes after rotator cuff te...
Increased adipocyte O2 consumption triggers HIF-1α, causing inflammation and insulin resistance in obesity.
Cell 157(6):1339 (2014)
Adipose tissue hypoxia and inflammation have been causally implicated in obesity-induced insulin resistance. Here, we report that, early in the course of high-fat diet (HFD) feeding and obesity, adipocyte respiration becomes uncoupled, leading to increased oxygen consumption and a state of relat...
Application of the [γ-32P] ATP kinase assay to study anabolic signaling in human skeletal muscle.
Journal of Applied Physiology 116(5):504 (2014)
AMPK (AMP-dependant protein kinase)-mTORC1 (mechanistic target of rapamycin in complex 1)-p70S6K1 (ribosomal protein S6 kinase 1 of 70 kDa) signaling plays a crucial role in muscle protein synthesis (MPS). Understanding this pathway has been advanced by the application of the Western blot (WB) t...
Knock-down of IL-1Ra in obese mice decreases liver inflammation and improves insulin sensitivity.
PLoS ONE 9(9):e107487 (2014)
Interleukin 1 Receptor antagonist (IL-1Ra) is highly elevated in obesity and is widely recognized as an anti-inflammatory cytokine. While the anti-inflammatory role of IL-1Ra in the pancreas is well established, the role of IL-1Ra in other insulin target tissues and the contribution of systemic ...
Interaction between lipid availability,endurance exercise and insulin sensitivity.
This chapter summarizes current knowledge regarding the interaction between lipid availability, endurance exercise, and insulin sensitivity. We discuss the role of lipid availability as a key mediator of insulin resistance in obesity, the proposed cellular mechanisms underlying this relationship...
Unraveling the complexities of SIRT1-mediated mitochondrial regulation in skeletal muscle.
Exercise and Sport Sciences Reviews 41(3):174 (2013)
Sirtuin 1 (SIRT1) is a purported central regulator of skeletal muscle mitochondrial biogenesis. Herein, we discuss our recent work using conditional mouse models, which highlight the complexities of SIRT1 biology in vivo, and question the role of SIRT1 in regulating mitochondrial function and mi...
Role of the cytoskeleton in muscle transcriptional responses to altered use.
Physiological Genomics 45(8):321 (2013)
In this work, the interaction between the loss of a primary component of the skeletal muscle cytoskeleton, desmin, and two common physiological stressors, acute mechanical injury and aging, were investigated at the transcriptional, protein, and whole muscle levels. The transcriptional response o...
Ceramides contained in LDL are elevated in type 2 diabetes and promote inflammation and skeletal muscle insulin resistance.
Diabetes 62(2):401 (2013)
Dysregulated lipid metabolism and inflammation are linked to the development of insulin resistance in obesity, and the intracellular accumulation of the sphingolipid ceramide has been implicated in these processes. Here, we explored the role of circulating ceramide on the pathogenesis of insulin...
Skeletal muscle Nur77 expression enhances oxidative metabolism and substrate utilization.
Journal of Lipid Research 53(12):2610 (2012)
Mitochondrial dysfunction has been implicated in the pathogenesis of type 2 diabetes. Identifying novel regulators of mitochondrial bioenergetics will broaden our understanding of regulatory checkpoints that coordinate complex metabolic pathways. We previously showed that Nur77, an orphan nuclea...
Attenuated Pik3r1 expression prevents insulin resistance and adipose tissue macrophage accumulation in diet-induced obese mice.
Diabetes 61(10):2495 (2012)
Obese white adipose tissue (AT) is characterized by large-scale infiltration of proinflammatory macrophages, in parallel with systemic insulin resistance; however, the cellular stimulus that initiates this signaling cascade and chemokine release is still unknown. The objective of this study was ...
NAD(+)/NADH and skeletal muscle mitochondrial adaptations to exercise.
American Journal of Physiology - Endocrinology ... 303(3):E308 (2012)
The pyridine nucleotides, NAD(+) and NADH, are coenzymes that provide oxidoreductive power for the generation of ATP by mitochondria. In skeletal muscle, exercise perturbs the levels of NAD(+), NADH, and consequently, the NAD(+)/NADH ratio, and initial research in this area focused on the contri...