A5063152297- Adipose Tissue and Metabolism
- Adipokines, Inflammation, and Metabolic Diseases
- Cardiovascular Disease and Adiposity
- Lipid metabolism and biosynthesis
- Metabolism, Diabetes, and Cancer
- Peroxisome Proliferator-Activated Receptors
- RNA Interference and Gene Delivery
- Pancreatic function and diabetes
- 14-3-3 protein interactions
- Mitochondrial Function and Pathology
- Muscle Physiology and Disorders
- Protein Kinase Regulation and GTPase Signaling
- CRISPR and Genetic Engineering
- Diet, Metabolism, and Disease
- Cancer, Lipids, and Metabolism
- Microbial Metabolic Engineering and Bioproduction
- Lipid metabolism and disorders
- Sirtuins and Resveratrol in Medicine
- Regulation of Appetite and Obesity
- PI3K/AKT/mTOR signaling in cancer
- Diabetes and associated disorders
- Microtubule and mitosis dynamics
- Photosynthetic Processes and Mechanisms
- Circular RNAs in diseases
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
University of Massachusetts Chan Medical School
2014-2025
UMass Memorial Medical Center
2025
Institute of Molecular Medicine
2003-2004
Adipose tissue plays a central role in the control of energy homeostasis through storage and turnover triglycerides secretion factors that affect satiety fuel utilization. Agents enhance insulin sensitivity, such as rosiglitazone, appear to exert their therapeutic effect adipose tissue, but precise mechanisms actions are unclear. Rosiglitazone changes morphological features protein profiles mitochondria 3T3-L1 adipocytes. To examine relevance these effects vivo, we studied white adipocytes...
White adipose tissue is an important endocrine organ involved in the control of whole-body metabolism, insulin sensitivity, and food intake. To better understand these functions, 3T3-L1 cell differentiation was studied by using combined proteomic genomic strategies. The proteomics approach developed here exploits velocity gradient centrifugation as alternative to isoelectric focusing for protein separation first dimension. A 20- 30-fold increase concentration numerous mitochondrial proteins...
Storage of energy as triglyceride in large adipose-specific lipid droplets is a fundamental need all mammals. Efficient sequestration fat adipocytes also prevents fatty acid overload skeletal muscle and liver, which can impair insulin signaling. Here we report that the Cide domain-containing protein Cidea, previously thought to be mitochondrial protein, colocalizes around with perilipin, regulator lipolysis. Cidea-GFP greatly enhances droplet size when ectopically expressed preadipocytes or...
Background— Adipose tissue expands in response to excess caloric intake, but individuals prone deposit visceral instead of subcutaneous adipose have higher risk metabolic disease. The role angiogenesis the expandability human depots is unknown. objective this study was measure and establish whether there a relationship between obesity, status, angiogenic properties these depots. Methods Results— Angiogenic capacity determined by quantifying capillary branch formation from explants embedded...
Using an siRNA-based screen, we identified the transcriptional corepressor RIP140 as a negative regulator of insulin-responsive hexose uptake and oxidative metabolism in 3T3-L1 adipocytes. Affymetrix GeneChip profiling revealed that depletion upregulates expression clusters genes pathways glucose uptake, glycolysis, TCA cycle, fatty acid oxidation, mitochondrial biogenesis, phosphorylation these cells. Conversely, show reexpression mouse embryonic fibroblasts derived from RIP140-null mice...
PPARgamma activators such as rosiglitazone (RSG) stimulate adipocyte differentiation and increase subcutaneous adipose tissue mass. However, in addition to preadipocyte differentiation, expansion requires neovascularization support increased numbers. Paradoxically, endothelial cell growth is potently inhibited by RSG vitro, raising the question of how this drug can induce an mass while inhibiting angiogenesis. We find that from mice treated with have capillary density. To determine whether...
The insulin-regulated glucose transporter GLUT4 is a key modulator of whole body homeostasis, and its selective loss in adipose tissue or skeletal muscle causes insulin resistance diabetes. Here we report an RNA interference-based screen protein kinases expressed adipocytes identify four negative regulators insulin-responsive transport: the PCTAIRE-1 (PCTK1), PFTAIRE-1 (PFTK1), IκB kinase α, MAP4K4/NIK. Integrin-linked was identified as positive regulator this process. We characterized one...
Adipose tissue (AT) inflammation and infiltration by macrophages is associated with insulin resistance type 2 diabetes in obese humans, offering a potential target for therapeutics. However, whether AT (ATMs) directly contribute to systemic glucose intolerance has not been determined. The reason the lack of methods ablate inflammatory genes expressed specifically localized within depots, leaving other tissues unaffected. Here we report that i.p. administration siRNA encapsulated glucan...
Adipose tissue (AT) inflammation is associated with systemic insulin resistance and hyperinsulinemia in obese rodents humans. A longstanding concept that may promote through downregulation of its receptor on target tissues. Here we tested the novel hypothesis also impairs sensitivity by specifically enhancing adipose inflammation.Circulating levels were reduced about 50% diet-induced genetically mice treatments diazoxide or streptozotocin, respectively. We then examined AT crown-like...
Abstract Obesity and type 2 diabetes are associated with disturbances in insulin-regulated glucose lipid fluxes severe comorbidities including cardiovascular disease steatohepatitis. Whole body metabolism is regulated by lipid-storing white adipocytes as well “brown” “brite/beige” that express thermogenic uncoupling protein 1 (UCP1) secrete factors favorable to metabolic health. Implantation of brown fat into obese mice improves tolerance, but translation humans has been stymied low...
Adipose tissue plays a central role in the control of energy homeostasis through storage and turnover triglycerides secretion factors that affect satiety fuel utilization. Agents enhance insulin sensitivity, such as rosiglitazone, appear to exert their therapeutic effect adipose tissue, but precise mechanisms actions are unclear. Rosiglitazone changes morphological features protein profiles mitochondria 3T3-L1 adipocytes. To examine relevance these effects vivo, we studied white adipocytes...
Phagocytic macrophages and dendritic cells are desirable targets for potential RNAi (RNA interference) therapeutics because they often mediate pathogenic inflammation autoimmune responses. We recently engineered a complex 5 component glucan-based encapsulation system siRNA (small interfering RNA) delivery to phagocytes. In experiments designed simplify this original formulation, we discovered that the amphipathic peptide Endo-Porter forms stable nanocomplexes with can potent gene silencing...
Proinflammatory pathways in adipose tissue macrophages (ATMs) can impair glucose tolerance obesity, but ATMs may also be beneficial as repositories for excess lipid that adipocytes are unable to store. To test this hypothesis, we selectively targeted visceral obese mice with siRNA against lipoprotein lipase (LPL), leaving within other organs unaffected. Selective silencing of ATM LPL decreased foam cell formation mice, consistent a reduced supply fatty acids from VLDL hydrolysis....
Here, we show that β adrenergic signaling coordinately upregulates de novo lipogenesis (DNL) and thermogenesis in subcutaneous white adipose tissue (sWAT), both effects are blocked mice lacking the cAMP-generating G protein-coupled receptor Gs (Adipo-GsαKO) adipocytes. However, UCP1 expression but not DNL activation requires rapamycin-sensitive mTORC1. Furthermore, β3-adrenergic agonist CL316243 readily thermogenic lipogenic genes cultured adipocytes, indicating additional regulators must...
Based on recent evidence that fatty acid synthase and endogenously produced derivatives are required for adipogenesis in 3T3-L1 adipocytes, we conducted a small interfering RNA-based screen to identify other acid-metabolizing enzymes may mediate this effect. Of 24 screened, stearoyl-CoA desaturase 2 (SCD2) was found be uniquely absolutely adipogenesis. Remarkably, SCD2 also controls the maintenance of adipocyte-specific gene expression fully differentiated including SCD1. Despite high...
Obesity promotes insulin resistance associated with liver inflammation, elevated glucose production, and type 2 diabetes. Although is attenuated in genetic mouse models that suppress systemic it not clear whether local resident macrophages liver, denoted Kupffer cells (KCs), directly contribute to this syndrome. We addressed question by selectively silencing the expression of master regulator NF-κB, KCs obese mice. used glucan-encapsulated small interfering RNA particles (GeRPs) silence gene...
Proper regulation of energy storage in adipose tissue is crucial for maintaining insulin sensitivity and molecules contributing to this process have not been fully revealed. Here we show that type II transmembrane protein tenomodulin (TNMD) upregulated insulin-resistant versus insulin-sensitive individuals, who were matched body mass index (BMI). TNMD expression increases human preadipocytes during differentiation, whereas silencing blocks adipogenesis. Upon high-fat diet feeding, transgenic...