A5040370626- Adipose Tissue and Metabolism
- Metabolism, Diabetes, and Cancer
- Adipokines, Inflammation, and Metabolic Diseases
- Diet and metabolism studies
- Pancreatic function and diabetes
- Muscle metabolism and nutrition
- Regulation of Appetite and Obesity
- PI3K/AKT/mTOR signaling in cancer
- Exercise and Physiological Responses
- Immune Cell Function and Interaction
- Endoplasmic Reticulum Stress and Disease
- Signaling Pathways in Disease
- Cancer, Hypoxia, and Metabolism
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Peptidase Inhibition and Analysis
- Lung Cancer Treatments and Mutations
- Sirtuins and Resveratrol in Medicine
- Blood properties and coagulation
- Skin Protection and Aging
- Parathyroid Disorders and Treatments
- Virus-based gene therapy research
- Cytokine Signaling Pathways and Interactions
- Genetics, Aging, and Longevity in Model Organisms
- Extracellular vesicles in disease
- Renal and related cancers
Roche (United States)
2015-2024
Roche (Switzerland)
2021
Ventana Research Corporation (United States)
2015-2018
University of Arizona
2007-2015
Yeshiva University
1996-2007
Whitehead Institute for Biomedical Research
2001-2006
Albert Einstein College of Medicine
1996-2005
Harvard University
2004
Massachusetts Institute of Technology
2001-2004
Boston University
2002
Adipocyte complement-related protein (30 kDa) (Acrp30), a secreted of unknown function, is exclusively expressed in differentiated adipocytes; its mRNA decreased obese humans and mice. Here we describe novel pharmacological properties the protease-generated globular head domain Acrp30 (gAcrp30). Acute treatment mice with gAcrp30 significantly elevated levels plasma free fatty acids caused either by administration high fat test meal or i.v. injection Intralipid. This effect was caused, at...
gACRP30, the globular subunit of adipocyte complement-related protein 30 kDa (ACRP30), improves insulin sensitivity and increases fatty acid oxidation. The mechanism by which gACRP30 exerts these effects is unknown. Here, we examined if activates AMP-activated kinase (AMPK), an enzyme that has been shown to increase muscle oxidation sensitivity. Incubation rat extensor digitorum longus (EDL), a predominantly fast twitch muscle, with (2.5 micro g/ml) for min led 2-fold in AMPK activity...
Acrp30/adiponectin is reduced in the serum of obese and diabetic individuals, genetic locus adiponectin linked to metabolic syndrome. Recombinant adiponectin, administered diet-induced mice, induced weight loss improved insulin sensitivity. In muscle liver, stimulates AMP-activated protein kinase activation fatty acid oxidation. To expression-clone molecules capable binding we transduced a C2C12 myoblast cDNA retroviral expression library into Ba/F3 cells panned infected on recombinant...
Biochemical, genetic, and animal studies in recent years have established a critical role for the adipokine Acrp30/adiponectin controlling whole-body metabolism, particularly by enhancing insulin sensitivity muscle liver, increasing fatty acid oxidation muscle. We describe widely expressed highly conserved family of adiponectin paralogs designated as C1q/tumor necrosis factor-α-related proteins (CTRPs) 1–7. In present study, we focus on mCTRP2, mouse paralog most similar to adiponectin. At...
Adipocyte complement-related protein of 30 kDa (Acrp30)/adiponectin is an adipocyte-derived hormone that affects lipid and glucose metabolism in muscle liver, but its physical biochemical properties are poorly characterized. Here we have used several approaches to show Acrp30 expressed purified from<i>Escherichia coli</i> human embryonic kidney 293T cells forms trimers hexamers; also produce a higher molecular weight species. Similar oligomers were found mouse serum as well 3T3-L1...
Thiazolidinediones (TZDs) are insulin-sensitizing agents used in the treatment of type 2 diabetes. A widely held view is that their action secondary to transcriptional events occur when TZDs bind nuclear receptor PPARgamma adipocyte and stimulate adipogenesis. It has been proposed this increases insulin sensitivity, at least part, by increasing expression release adiponectin, an adipokine activates fuel-sensing enzyme AMP-activated protein kinase (AMPK). In study, we report also acutely...
Dysregulation of GLUT4, the insulin-responsive glucose transporter, is associated with insulin resistance in skeletal muscle. Although muscle major target action, GLUT4 has not been linked causally to whole-body sensitivity and regulation homeostasis. To address this, we generated a line transgenic mice that overexpresses We demonstrate restricted overexpression fast-twitch muscles myosin light chain (MLC)–GLUT4 induces 2.5-fold increase insulin-stimulated 2-deoxyglucose uptake...
Introduction Fibroblast activation protein (FAP) is predominantly upregulated in various tumor microenvironments and scarcely expressed normal tissues. Methods We analyzed FAP across 1216 tissue samples covering 23 types 70 subtypes. Results Elevated levels were notable breast, pancreatic, esophageal, lung cancers. Using immunohistochemistry RNAseq, a correlation between gene expression was found. Evaluating FAP’s clinical significance, we assessed 29 cohorts from 12 trials, including both...
There is great interest in the structure of adiponectin as its oligomeric state may specify biological activities. It occurs a trimer, hexamer and high molecular weight complex. Epidemiological data indicate that form significant with low serum levels type 2 diabetics but to date, has not been well‐defined. To resolve this issue, characterization oligomer from bovine 3T3‐L1 adipocytes by sedimentation equilibrium centrifugation gel electrophoresis respectively, was carried out, revealing it...
OBJECTIVE Tankyrase (TNKS) is a Golgi-associated poly-ADP-ribose polymerase that implicated in the regulation of GLUT4 trafficking 3T3-L1 adipocytes. Its chromosomal locus 8p23.1 linked to monogenic forms diabetes certain kindred. We hypothesize TNKS involved energy homeostasis mammals. RESEARCH DESIGN AND METHODS Gene-trap techniques were used ablate expression mice. Homozygous and wild-type littermates maintained on standard chow compared. RESULTS Wild-type mice express protein abundantly...
Recent studies reported abnormal alpha-synuclein deposition in biopsy-accessible sites of the peripheral nervous system Parkinson's disease (PD). This has considerable implications for clinical diagnosis. Moreover, if occurs early, it may enable tissue diagnosis prodromal PD.
To understand the long-term metabolic and functional consequences of increased GLUT4 content, intracellular substrate utilization was investigated in isolated muscles transgenic mice overexpressing selectively fast-twitch skeletal muscles. Rates glycolysis, glycogen synthesis, glucose oxidation, free fatty acid (FFA) oxidation as well content were assessed EDL (fast-twitch) soleus (slow-twitch) from female male MLC-GLUT4 control mice. In EDL, influx predominantly led to glycolysis. contrast,...
Normal and pathological stressors engage the AMP-activated protein kinase (AMPK) signalling axis to protect cell from energetic pressures. Sex steroid hormones also play a critical role in energy metabolism significantly modify progression of cardiac disease, diabetes/obesity cancer. AMPK is targeted by 17β-oestradiol (E2), main circulating oestrogen, but mechanism which E2 activates currently unknown. Using an oestrogen receptor α/β (ERα/β) positive (T47D) breast cancer line, we validated...
The ability of muscles from Glut 4-null mice to take up and metabolize glucose has been studied in the isolated white EDL red soleus muscles. In male or female mice, basal deoxyglucose uptake was lower than control not stimulated by insulin. parallel, glycogen synthesis content were decreased. Soleus took twice more absence insulin muscles, but did respond females, measured hormone similar mice. This twofold threefold Basal increased 4- 2.2-fold null respectively, compared controls, had no...
We have taken the approach of introducing muscle-specific myosin light chain (MLC)-GLUT4 transgene into GLUT4-null background to assess relative role muscle and adipose tissue GLUT4 in etiology phenotype. The resulting MLC-GLUT4-null mice express predominantly fast-twitch extensor digitorum longus (EDL) muscle. is nearly absent female white (WAT) slow-twitch soleus both sexes mice. content male WAT 20% that control In transgenically complemented EDL muscle, 2-deoxyglucose (2-DOG) uptake was...
Impaired skeletal muscle glucose utilization under insulin action is a major defect in the etiology of type 2 diabetes. This underscored by new mouse model diabetes generated genetic disruption one allele transporter 4 (GLUT4+/-), insulin-responsive and adipose tissue. Male GLUT4+/- mice exhibited decreased GLUT4 expression uptake that accompanied impaired whole-body utilization, hyperinsulinemia, hyperglycemia, heart histopathology. To determine whether development diabetic phenotype can be...
Adiponectin is a circulating insulin-sensitizing hormone that homooligomerizes into trimers, hexamers, and higher molecular weight (HMW) species. Low levels of HMW adiponectin appear to increase the risk for insulin resistance. Currently, assembly oligomers and, consequently, mechanisms responsible decreased in resistance are not well understood. In work reported here, we analyzed reassembly most abundant species, octadecamer, following its collapse smaller vitro. Purified bovine serum...
Abstract Background Adiponectin is an adipocyte-secreted hormone with insulin-sensitizing and anti-inflammatory actions. The assembly of trimeric, hexameric, higher molecular weight (HMW) species adiponectin a topic significant interest because physiological actions are oligomer-specific. In addition, example oxidative oligomerization multi-subunit protein complexes in endoplasmic reticulum (ER). Results We previously reported that trimers assemble into HMW via intermediates stabilized by...