A5006982292- Adipokines, Inflammation, and Metabolic Diseases
- Adipose Tissue and Metabolism
- Peroxisome Proliferator-Activated Receptors
- Endoplasmic Reticulum Stress and Disease
- Pancreatic function and diabetes
- Regulation of Appetite and Obesity
- Liver Disease Diagnosis and Treatment
- Cholesterol and Lipid Metabolism
- Autophagy in Disease and Therapy
- Cancer, Lipids, and Metabolism
- Diet, Metabolism, and Disease
- Diet and metabolism studies
- Diabetes and associated disorders
- Metabolism, Diabetes, and Cancer
- Immune Cell Function and Interaction
- Lipid metabolism and biosynthesis
- Inflammatory mediators and NSAID effects
- Mitochondrial Function and Pathology
- Lipid metabolism and disorders
- Cardiovascular Disease and Adiposity
- Immune Response and Inflammation
- Fatty Acid Research and Health
- Eicosanoids and Hypertension Pharmacology
- Atherosclerosis and Cardiovascular Diseases
- Cytokine Signaling Pathways and Interactions
Broad Institute
2016-2025
Harvard University
2012-2024
Boston University
2022-2023
Vanderbilt University Medical Center
2002-2016
Massachusetts Institute of Technology
2010-2016
Oregon Health & Science University
2016
Bilkent University
2011-2016
Dana-Farber/Harvard Cancer Center
2014
Harvard University Press
2001-2014
MRC Epidemiology Unit
2014
Tumor necrosis factor-α (TNF-α) has been shown to have certain catabolic effects on fat cells and whole animals. An induction of TNF-α messenger RNA expression was observed in adipose tissue from four different rodent models obesity diabetes. protein also elevated locally systemically. Neutralization obese fa / rats caused a significant increase the peripheral uptake glucose response insulin. These results indicate role for particularly insulin resistance diabetes that often accompany obesity.
Obesity contributes to the development of type 2 diabetes, but underlying mechanisms are poorly understood. Using cell culture and mouse models, we show that obesity causes endoplasmic reticulum (ER) stress. This stress in turn leads suppression insulin receptor signaling through hyperactivation c-Jun N-terminal kinase (JNK) subsequent serine phosphorylation substrate-1 (IRS-1). Mice deficient X-box-binding protein-1 (XBP-1), a transcription factor modulates ER response, develop resistance....
Obesity is frequently associated with insulin resistance and abnormal glucose homeostasis. Recent studies in animal models have indicated that TNF-alpha plays an important role mediating the of obesity through its overexpression fat tissue. However, mechanisms linking to diabetes humans remain largely unknown. In this study we examined expression pattern mRNA adipose tissues from 18 control 19 obese premenopausal women by Northern blot analysis. protein concentrations plasma conditioned...
Tumor necrosis factor-α (TNF-α) is an important mediator of insulin resistance in obesity and diabetes through its ability to decrease the tyrosine kinase activity receptor (IR). Treatment cultured murine adipocytes with TNF-α was shown induce serine phosphorylation substrate 1 (IRS-1) convert IRS-1 into inhibitor IR vitro. Myeloid 32D cells, which lack endogenous IRS-1, were resistant TNF-α-mediated inhibition signaling, whereas transfected cells that express very sensitive this effect...
Endoplasmic reticulum (ER) stress is a key link between obesity, insulin resistance, and type 2 diabetes. Here, we provide evidence that this mechanistic can be exploited for therapeutic purposes with orally active chemical chaperones. 4-Phenyl butyric acid taurine-conjugated ursodeoxycholic alleviated ER in cells whole animals. Treatment of obese diabetic mice these compounds resulted normalization hyperglycemia, restoration systemic sensitivity, resolution fatty liver disease, enhancement...
Insulin resistance is a common problem associated with infections and cancer and, most importantly, the central component of non-insulin-dependent diabetes mellitus. We have recently shown that tumor necrosis factor (TNF) alpha key mediator insulin in animal models Here, we investigate how TNF-alpha interferes action. Chronic exposure adipocytes to low concentrations strongly inhibits insulin-stimulated glucose uptake. Concurrently, treatment causes moderate decrease autophosphorylation...
Fatty acid binding proteins (FABPs) are small cytoplasmic that expressed in a highly tissue-specific manner and bind to fatty acids such as oleic retinoic acid. Mice with null mutation aP2 , the gene encoding adipocyte FABP, were developmentally metabolically normal. The -deficient mice developed dietary obesity but, unlike control mice, they did not develop insulin resistance or diabetes. Also their obese wild-type counterparts, −/− animals failed express adipose tissue tumor necrosis...
Insulin resistance is an important metabolic abnormality often associated with infections, cancer, obesity, and especially non-insulin-dependent diabetes mellitus (NIDDM). We have previously demonstrated that tumor necrosis factor-alpha produced by adipose tissue a key mediator of insulin in animal models obesity-diabetes. However, the mechanism which TNF-alpha interferes action not known. Since defective receptor (IR) tyrosine kinase activity has been observed obesity NIDDM, we measured IR...