A5011853620- Adipose Tissue and Metabolism
- Metabolism, Diabetes, and Cancer
- Pancreatic function and diabetes
- Adipokines, Inflammation, and Metabolic Diseases
- Diet and metabolism studies
- Regulation of Appetite and Obesity
- Retinoids in leukemia and cellular processes
- Protein Tyrosine Phosphatases
- Peroxisome Proliferator-Activated Receptors
- Antioxidant Activity and Oxidative Stress
- Muscle metabolism and nutrition
- Fatty Acid Research and Health
- Muscle Physiology and Disorders
- Biochemical Analysis and Sensing Techniques
- Diet, Metabolism, and Disease
- Protein Kinase Regulation and GTPase Signaling
- Diabetes Treatment and Management
- Metabolomics and Mass Spectrometry Studies
- Diabetes and associated disorders
- Galectins and Cancer Biology
- Retinal Diseases and Treatments
- PI3K/AKT/mTOR signaling in cancer
- Lipid metabolism and biosynthesis
- Cholesterol and Lipid Metabolism
- Mitochondrial Function and Pathology
Beth Israel Deaconess Medical Center
2015-2024
Harvard University
2015-2024
Lemuel Shattuck Hospital
2024
College of the Atlantic
2024
Hadassah Medical Center
2004-2023
Broad Institute
2023
Yale University
2001-2020
National Institutes of Health
1985-2020
Brigham and Women's Hospital
1991-2020
Rockefeller University
2020
Caloric restriction has been shown to increase longevity in organisms ranging from yeast mammals. In some organisms, this associated with a decreased fat mass and alterations insulin/insulin-like growth factor 1 (IGF-1) pathways. To further explore these associations enhanced longevity, we studied mice fat-specific insulin receptor knockout (FIRKO). These animals have reduced are protected against age-related obesity its subsequent metabolic abnormalities, although their food intake is...
Insulin resistance has a causal role in type 2 diabetes. Serum levels of retinol-binding protein 4 (RBP4), secreted by adipocytes, are increased insulin-resistant states. Experiments mice suggest that elevated RBP4 cause insulin resistance. We sought to determine whether serum correlate with and change after an intervention improves sensitivity. also determined associated reduced expression glucose transporter (GLUT4) early pathological feature resistance.We measured RBP4, resistance,...
Protein-tyrosine phosphatase 1B (PTP-1B) is a major protein-tyrosine that has been implicated in the regulation of insulin action, as well other signal transduction pathways. To investigate role PTP-1B vivo, we generated homozygotic PTP-1B-null mice by targeted gene disruption. PTP-1B-deficient have remarkably low adiposity and are protected from diet-induced obesity. Decreased due to marked reduction fat cell mass without decrease adipocyte number. Leanness accompanied increased basal...
We examined the hypothesis that insulin resistance in skeletal muscle promotes development of atherogenic dyslipidemia, associated with metabolic syndrome, by altering distribution pattern postprandial energy storage. Following ingestion two high carbohydrate mixed meals, net glycogen synthesis was reduced approximately 60% young, lean, insulin-resistant subjects compared a similar cohort age-weight-body mass index-activity-matched, insulin-sensitive, control subjects. In contrast, hepatic...
The mutant gene responsible for obesity in the ob/ob mouse was recently identified by positional cloning (Zhang Y., R. Proenca, M. Maffel, Barone, L. Leopold, and J.M. Friedman. 1994. Nature (Lond.) 372:425). encoded protein to represent "adipostat" signal reflecting state of energy stores. We confirm that adipocyte is source ob mRNA predicted 16-kD present rodent serum as detected Western blot. To evaluate hypothesis it might an adipostat, we assessed levels expression adipose cells tissue...
To gain insight into the molecular pathogenesis of obesity and specifically role nutrient partitioning in development obesity, we overexpressed insulin-responsive glucose transporter (GLUT4) transgenic mice under control fat-specific aP2 fatty acid-binding protein promoterlenhancer.Two lines were generated, which GLUT4 6-9-fold white fat 3-5-fold brown with no overexpression other tissues.In vivo tolerance was enhanced mice.In isolated epididymal, parametrial, subcutaneous adipose cells from...
β3-Adrenergic receptors (β3-ARs) are expressed predominantly in white and brown adipose tissue, β3-selective agonists potential anti-obesity drugs. However, the role of β3-ARs normal physiology is unknown. To address this issue, homologous recombination was used to generate mice that lack β3-ARs. This accomplished by direct injection a DNA-targeting construct into mouse zygotes. Twenty-three transgenic were generated, which two had targeted disruption β3-AR gene. Mice homozygous for...