A5075998503- Adipose Tissue and Metabolism
- Metabolism, Diabetes, and Cancer
- Pancreatic function and diabetes
- Diet and metabolism studies
- Adipokines, Inflammation, and Metabolic Diseases
- Muscle metabolism and nutrition
- Metabolomics and Mass Spectrometry Studies
- Muscle Physiology and Disorders
- Sirtuins and Resveratrol in Medicine
- Biochemical effects in animals
- Liver Disease Diagnosis and Treatment
- Cardiovascular and exercise physiology
- PI3K/AKT/mTOR signaling in cancer
- Regulation of Appetite and Obesity
- Diet, Metabolism, and Disease
- Metabolism and Genetic Disorders
- Nitric Oxide and Endothelin Effects
- Cancer, Hypoxia, and Metabolism
- Glycogen Storage Diseases and Myoclonus
- Pharmacological Effects and Assays
- Hippo pathway signaling and YAP/TAZ
- Exercise and Physiological Responses
- Proteoglycans and glycosaminoglycans research
- Mitochondrial Function and Pathology
- Diabetes and associated disorders
Vanderbilt University
2016-2025
Vanderbilt University Medical Center
2015-2024
University of California, San Diego
2024
University of Fort Lauderdale
2023
John F. Kennedy Center for the Performing Arts
2021
Universitat Jaume I
2019
Nashville Oncology Associates
2019
Cornell University
2017
Inserm
2009-2014
Université Paris Cité
2009-2014
AMP-activated protein kinase (AMPK) is a sensor of cellular energy status that plays central role in skeletal muscle metabolism. We used muscle-specific AMPKα1α2 double-knockout (mdKO) mice to provide direct genetic evidence the physiological importance AMPK regulating exercise capacity, mitochondrial function, and contraction-stimulated glucose uptake. Exercise performance was significantly reduced mdKO mice, with reduction maximal force production fatigue resistance. An increase proportion...
Natriuretic regulation of extracellular fluid volume homeostasis includes suppression the renin-angiotensin-aldosterone system, pressure natriuresis, and reduced renal nerve activity, actions that concomitantly increase urinary Na+ excretion lead to increased urine volume. The resulting natriuresis-driven diuretic water loss is assumed control Here, we have demonstrated concentration, therefore conservation, an important system for formation in mice humans across various levels salt intake....
Interactions between lineage-determining and activity-dependent transcription factors determine single-cell identity function within multicellular tissues through incompletely known mechanisms. By assembling a atlas of chromatin state human islets, we identified β cell subtypes governed by either high or low activity the factor pancreatic duodenal homeobox-1 (PDX1). cells with reduced PDX1 displayed increased accessibility at latent nuclear κB (NF-κB) enhancers. Pdx1 hypomorphic mice...
The chronic inflammatory state that accompanies obesity is a major contributor to insulin resistance and other dysfunctional adaptations in adipose tissue. Cellular secreted factors promote the milieu of obesity, but transcriptional pathways drive these processes are not well described. Although canonical transcription factor NF-κB considered be driver adipocyte inflammation, members interferon regulatory (IRF) family may also play role this process. Here, we determined IRF3 expression...
Protein hyperacetylation is associated with glucose intolerance and insulin resistance, suggesting that the enzymes regulating acetylome play a role in this pathological process. Sirtuin 3 (SIRT3), primary mitochondrial deacetylase, has been linked to energy homeostasis. Thus, it hypothesized dysregulation of acetylation state, via genetic deletion SIRT3, will amplify deleterious effects high-fat diet (HFD). Hyperinsulinemic-euglycemic clamp experiments show, for first time, mice lacking...
An acute bout of exercise increases glucose uptake in skeletal muscle by an insulin-independent mechanism. In the period after exercise, insulin sensitivity to increased is enhanced. The molecular mechanisms underpinning this phenomenon are poorly understood but appear involve cell surface abundance GLUT4. While proximal signaling does not seem mediate effect, elevated phosphorylation TBC1D4, a downstream target both (Akt) and (AMPK) signaling, appears play role. main purpose study was...
Increased deposition of specific extracellular matrix (ECM) components is a characteristic insulin-resistant skeletal muscle. Hyaluronan (HA) major constituent the ECM. The hypotheses that 1) HA content increased in ECM muscle and 2) reduction by long-acting pegylated human recombinant PH20 hyaluronidase (PEGPH20) reverses high-fat (HF) diet-induced insulin resistance were tested. We show was HF obese (DIO) mice treatment PEGPH20, which dose-dependently reduced ECM, decreased fat mass,...
Mammals are protected from changes in environmental temperature by altering energetic processes that modify heat production. Insulin is the dominant stimulus of glucose uptake and metabolism, which fundamental for thermogenic processes. The purpose this work was to determine interaction ambient induced energy expenditure (EE) on insulin sensitivity fluxes. Short-term adaptive responses thermoneutral (TN, ∼28°C) room (laboratory) (RT, ∼22°C) were studied mice. This range does not cause...
Nearly half of adults have hypertension, a major risk factor for cardiovascular disease. Mitochondrial hyperacetylation is linked to but the role acetylation specific proteins not clear. We hypothesized that mitochondrial CypD (cyclophilin D) at K166 contributes endothelial dysfunction and hypertension.
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Muscle insulin resistance is associated with a reduction in vascular endothelial growth factor (VEGF) action and muscle capillary density. We tested the hypothesis that rarefaction critically contributes to etiology of chow-fed mice skeletal cardiac VEGF deletion (mVEGF−/−) wild-type littermates (mVEGF+/+) on C57BL/6 background. The mVEGF−/− had an ∼60% ∼50% decrease capillaries muscle, respectively. augmented fasting glucose turnover. Insulin-stimulated whole-body disappearance was blunted...
AMPK (AMP-activated protein kinase) is an attractive therapeutic drug target for treating metabolic disorders. We studied the effects of activator developed by Merck (ex229 from patent application WO2010036613), comparing chemical activation with contraction in intact incubated skeletal muscles. also compared ex229 those Abbott A769662 compound and AICAR (5-amino-4-imidazolecarboxamide riboside). In rat epitrochlearis muscle, dose-dependently increased activity α1-, α2-, β1- β2-containing...
The liver responds to an increase in blood glucose levels the postprandial state by uptake of and conversion glycogen. Liver glycogen synthase (GYS2), a key enzyme synthesis, is controlled complex interplay between allosteric activator glucose-6-phosphate (G6P) reversible phosphorylation through kinase-3 glycogen-associated form protein phosphatase 1. Here, we initially performed mutagenesis analysis identified residue (Arg582) required for activation GYS2 G6P. We then used Arg582Ala knockin...
Nutrition and physical activity have profound effects on skeletal muscle metabolism growth. Regulation of mass depends a thin balance between growth-promoting growth-suppressing factors. Over the past decade, mammalian target rapamycin (mTOR) kinase has emerged as an essential factor for growth by mediating anabolic response to nutrients, insulin, insulin-like factors resistance exercise. As opposed mTOR signaling pathway, AMP-activated protein (AMPK) is switched during starvation endurance...