A5076988758- Adipose Tissue and Metabolism
- Peroxisome Proliferator-Activated Receptors
- Metabolism, Diabetes, and Cancer
- Lipid metabolism and biosynthesis
- Caveolin-1 and cellular processes
- Pancreatic function and diabetes
- Liver Disease Diagnosis and Treatment
- Cancer, Hypoxia, and Metabolism
- Lipid metabolism and disorders
- Lymphatic System and Diseases
- Regulation of Appetite and Obesity
- Nuclear Structure and Function
- Muscle metabolism and nutrition
- Cancer-related Molecular Pathways
- Growth Hormone and Insulin-like Growth Factors
- Cellular transport and secretion
- Extracellular vesicles in disease
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Body Contouring and Surgery
- Ubiquitin and proteasome pathways
- Biochemical effects in animals
- Endoplasmic Reticulum Stress and Disease
- Diet and metabolism studies
- Neuroblastoma Research and Treatments
- Helicobacter pylori-related gastroenterology studies
Washington University in St. Louis
2012-2024
Center for Human Genetics
2014
Hebrew University of Jerusalem
2008-2009
Movement of circulating fatty acids (FAs) to parenchymal cells requires their transfer across the endothelial cell (EC) barrier. The multiligand receptor cluster differentiation 36 (CD36) facilitates tissue FA uptake and is expressed in ECs such as myocytes adipocytes. Whether FAs dependent on EC or CD36, both, unknown. Using a cell-specific deletion approach, we show that EC, but not cell, CD36 increased fasting plasma postprandial triglycerides. EC-Cd36–KO mice had reduced radiolabeled...
Increases in muscle energy needs activate AMPK and induce sarcolemmal recruitment of the fatty acid (FA) translocase CD36. The resulting rises FA uptake oxidation are tightly correlated, suggesting coordinated regulation. We explored possibility that membrane CD36 signaling might influence activation. show, using several cell types, including myocytes, expression suppresses AMPK, keeping it quiescent, while mediates activation by FA. These dual effects reflect presence a protein complex with...
BACKGROUND. Obesity is associated with insulin resistance and increased intrahepatic triglyceride (IHTG) content, both of which are key risk factors for diabetes cardiovascular disease. However, a subset obese people does not develop these metabolic complications. Here, we tested the hypothesis that defined by IHTG content sensitivity as "metabolically normal obese" (MNO), but those abnormal (MAO), protected from adverse effects weight gain. METHODS. Body composition, multiorgan sensitivity,...
The FA translocase cluster of differentiation 36 (CD36) facilitates uptake by the myocardium, and its surface recruitment in cardiomyocytes is induced insulin, AMP-dependent protein kinase (AMPK), or contraction. Dysfunction CD36 trafficking contributes to disordered cardiac utilization promotes progression disease. Akt substrate 160 (AS160) Rab GTPase-activating (GAP) a key regulator vesicular trafficking, activity modulated via phosphorylation. Our study documents that AS160 mediates...
Abstract Endothelial cell (EC) CD36 controls tissue fatty acid (FA) uptake. Here we examine how ECs transfer FAs. FA interaction with apical membrane induces Src phosphorylation of caveolin-1 tyrosine-14 (Cav-1Y14) and ceramide generation in caveolae. Ensuing fission caveolae yields vesicles containing FAs, that are secreted basolaterally as small (80–100 nm) exosome-like extracellular (sEVs). We visualize transwells EC FAs sEVs to underlying myotubes. In mice EC-expression the exosome...
CD36 has been linked to the etiology of insulin resistance and inflammation. We explored its function in regulating adipose tissue lipolysis, which influences fat accumulation by liver muscle overall metabolism. Knockdown differentiated 3T3-L1 adipocytes decreased lipolysis response 10 μM β-adrenergic agonist isoproterenol (by 42%), adenyl cyclase activator forskolin 32%), 500 phosphodiesterase (PDE) inhibitor isobutylmethylxanthine 33%). All three treatments knockdown were associated with...
During reduced energy intake, skeletal muscle maintains homeostasis by rapidly suppressing insulin-stimulated glucose utilization. Loss of this adaptation is observed with deficiency the fatty acid transporter CD36. A similar loss also characteristic insulin-resistant state where CD36 dysfunctional. To elucidate what links to utilization, we examined whether signaling might influence insulin action. First, show that deletion specific reduces expression and metabolism genes. It decreases...
<p dir="ltr"><b>Objective</b>: Weight loss improves insulin sensitivity in people with obesity and type 2 diabetes. However, the mechanisms responsible for this effect are unclear. We hypothesized that alterations adipose tissue biology tissue-related factors plasma involved mediating systemic metabolic benefits of weight loss.</p><p dir="ltr"><b>Research Design Methods</b>: evaluated blood samples obtained from ten adults diabetes before after...
<p dir="ltr"><b>Objective</b>: Weight loss improves insulin sensitivity in people with obesity and type 2 diabetes. However, the mechanisms responsible for this effect are unclear. We hypothesized that alterations adipose tissue biology tissue-related factors plasma involved mediating systemic metabolic benefits of weight loss.</p><p dir="ltr"><b>Research Design Methods</b>: evaluated blood samples obtained from ten adults diabetes before after...
OBJECTIVE Weight loss improves insulin sensitivity in people with obesity and type 2 diabetes. However, the mechanisms responsible for this effect are unclear. We hypothesized that alterations adipose tissue biology tissue-related factors plasma involved mediating systemic metabolic benefits of weight loss. RESEARCH DESIGN AND METHODS evaluated blood samples obtained from 10 adults diabetes before after marked (16–20%) &gt;50% increase whole-body sensitivity, assessed by using...
Insulin/IGF-1 signaling plays a pivotal role in the regulation of cellular homeostasis through its control glucose metabolism as well due to effects on cell proliferation. Aberrant insulin has been repeatedly implicated uncontrolled growth and malignant transformations. TBC1D3 is hominoid specific gene previously identified an oncogene breast prostate cancers. Our efforts identify molecular mechanisms TBC1D3-induced oncogenesis revealed insulin/IGF-1 pathway. We document here that...
The role played by long chain fatty acids (LCFA) in promoting energy expenditure is confounded their dual function as substrates for oxidation and putative classic uncouplers of mitochondrial oxidative phosphorylation. LCFA analogs the MEDICA (MEthyl-substituted DICarboxylic Acids) series are neither esterified into lipids nor beta-oxidized may thus simulate uncoupling activity natural vivo, independently substrate role. Treatment rats or cell lines with results low conductance gating...
Expression of the hominoid-specific TBC1D3 oncoprotein enhances growth factor receptor signaling and subsequently promotes cellular proliferation survival. Here we report that is degraded in response to signaling, suggesting expression regulated by a factor-driven negative feedback loop. To gain better understanding how regulated, studied effects on post-translational processing turnover. Using yeast two-hybrid screen, identified CUL7, scaffolding subunit CUL7 E3 ligase complex, as...
The gastric epithelium is often exposed to injurious elements and failure of appropriate healing predisposes ulcers, hemorrhage, ultimately cancer. We examined the function CD36, a protein linked disease homeostasis. used tamoxifen model injury in mice null for Cd36 (Cd36-/-), with deletion parietal cells (PC-Cd36-/-) or endothelial (EC-Cd36-/-). CD36 expresses on corpus ECs, PC basolateral membranes, gastrin ghrelin cells. Stomachs Cd36-/- have altered gland organization secretion, more...
Muscle sn-1,2-diacylglycerol (DAG) and C18:0 ceramide accumulation in sarcolemmal mitochondrial compartments have been proposed to regulate muscle insulin sensitivity. Here, we evaluated whether weight loss-induced improvements sensitivity were associated with changes sn-1,2-DAG content people obesity type 2 diabetes. We measured skeletal sensitivity, assessed by using the hyperinsulinemic-euglycemic clamp procedure conjunction stable isotopically labeled glucose tracer infusion, contents...
Dysfunction of endothelial insulin delivery to muscle associates with resistance. CD36, a fatty acid transporter and modulator signaling is abundant in cells, especially capillaries. Humans inherited 50% reduction CD36 expression have dysfunction but whether it associated resistance unclear. Using hyperinsulinemic/euglycemic clamps Cd36-/- wildtype mice, deficient humans matched controls we found that mice enhanced systemic glucose disposal despite unaltered transendothelial transfer...