A5018793445- Adipose Tissue and Metabolism
- Adipokines, Inflammation, and Metabolic Diseases
- Regulation of Appetite and Obesity
- Stress Responses and Cortisol
- Pancreatic function and diabetes
- Peroxisome Proliferator-Activated Receptors
- Mitochondrial Function and Pathology
- Diet and metabolism studies
- Diabetes Management and Research
- Diabetes and associated disorders
- Inflammasome and immune disorders
- Lipid metabolism and biosynthesis
- Immune Cell Function and Interaction
- Endoplasmic Reticulum Stress and Disease
- Neuroendocrine regulation and behavior
- Adrenal Hormones and Disorders
- Advanced Glycation End Products research
- Cytokine Signaling Pathways and Interactions
- Adenosine and Purinergic Signaling
- Diet, Metabolism, and Disease
- Metabolism, Diabetes, and Cancer
- S100 Proteins and Annexins
- Sirtuins and Resveratrol in Medicine
- DNA Repair Mechanisms
- Apelin-related biomedical research
Harvard University
2007-2024
Boston University
2022-2023
Harvard University Press
2012
University of Toronto
2001-2008
Canada Research Chairs
2004-2008
Beth Israel Deaconess Medical Center
2006-2007
University of New Brunswick
2004
Czech Academy of Sciences, Institute of Physiology
2001-2002
TLR4 is the receptor for LPS and plays a critical role in innate immunity. Stimulation of activates proinflammatory pathways induces cytokine expression variety cell types. Inflammatory are activated tissues obese animals humans play an important obesity-associated insulin resistance. Here we show that nutritional fatty acids, whose circulating levels often increased obesity, activate signaling adipocytes macrophages capacity acids to induce inflammatory adipose cells or tissue blunted...
Propionate activates the insulin counter-regulatory hormonal response in mice, resulting resistance and weight gain.
Macrophage recruitment to adipose tissue in obesity contributes enhanced inflammatory activity and thus may underlie obesity-associated metabolic dysfunction. Obese exhibits increases CC chemokine ligand 2 (CCL2, or monocyte chemoattractant protein-1), an important macrophage-recruiting factor. We therefore hypothesized that elevated CCL2 contribute macrophage recruitment. Male 6-week-old CCL2(-/-) wild-type mice (n = 11-14 per group) were fed standard high-fat diets until 34 weeks of age....
Hyperglycemia is a result of impaired insulin action on glucose production and disposal, major target antidiabetic therapies. The study insulin-independent regulatory mechanisms metabolism may identify new strategies to lower blood sugar levels. Here we demonstrate an unexpected metabolic function for IL-13 in the control hepatic production. Th2 cytokine known mediate macrophage alternative activation. Genetic ablation Il-13 mice (Il-13–/–) resulted hyperglycemia, which progressed resistance...
Accumulation of DNA damage is intricately linked to aging, aging-related diseases and progeroid syndromes such as Cockayne syndrome (CS). Free radicals from endogenous oxidative energy metabolism can DNA, however the potential acute or chronic modulate cellular and/or organismal remains largely unexplored. We modeled genotoxic stress using a repair-deficient Csa-/-|Xpa-/- mouse model CS. Exogenous was in mice vivo primary cells vitro treated with different genotoxins giving rise diverse...
In adipocytes, suppressor of cytokine signaling (SOCS)3 deficiency increases insulin-stimulated insulin receptor substrate (IRS)-1 and -2 phosphorylation, IRS-associated phosphatidylinositol 3 kinase activity, glucose uptake. Moreover, SOCS3 is required for tumor necrosis factor-α full inhibition IRS-1 Whether also inhibits adipocyte in vivo whether this action further affects systemic sensitivity not clear. We therefore generated a transgenic mouse (aP2-SOCS3 mouse) overexpressing adipose...
A monoclonal antibody to fatty acid–binding protein aP2 has antidiabetic effects on glucose output and utilization.
The adipocyte is central to organismal metabolism and exhibits significant functional morphological plasticity during its formation lifespan. Remarkable transformations of this cell occur obesity lactation, thus it essential gain a better understanding function in these two metabolic processes. Considering the critical importance cellular organelle endoplasmic reticulum (ER) adapting fluctuations synthetic processes, we explored role XBP1, regulator ER adaptive responses, function....
Abstract Aims Obesity is a risk factor of abdominal aortic aneurysm (AAA). Inflammatory cytokine interleukin-18 (IL18) has two receptors: IL18 receptor (IL18r) and Na-Cl co-transporter (NCC). In human mouse AAA lesions, colocalizes to its receptors at regions rich in adipocytes, suggesting role adipocytes promoting actions development. Methods results We localized both IL18r NCC lesions. Murine development required receptors. binding these increased enriched or adjacent perivascular adipose...
Although increased hypothalamo-pituitary-adrenocortical (HPA) activity has been reported in diabetic patients, the mechanisms underlying hyperactivation are still unclear. We investigated whether alterations pituitary, adrenal and/or glucocorticoid negative feedback sensitivity diabetes responsible for 1) impaired HPA response to stress and 2) basal of axis. Normal control, untreated streptozotocin-diabetic insulin-treated rats were chronically catheterized. Eight days following surgery,...
Increased hypothalamo-pituitary-adrenocortical (HPA) activity in diabetes is likely important the development of some pathologies associated with disorder. We hypothesized that central regulation HPA differs among normal, streptozotocin (STZ)-diabetic, and insulin-treated diabetic rats. Blood glucose, ACTH, corticosterone were elevated, 8 d after inducing diabetes. Insulin treatment normalized these parameters. Plasma norepinephrine was similar all groups, but epinephrine lower STZ-diabetic...
We recently established that in addition to plasma adrenocorticotrophic hormone (ACTH) and corticosterone, hypothalamic corticotrophin-releasing (CRH) mRNA hippocampal type 1 glucocorticoid receptor (GR1) were also upregulated uncontrolled streptozotocin-induced diabetes. In the current study, control, diabetic, insulin-treated diabetic rats underwent a hyperinsulinemic-hypoglycemic glucose clamp evaluate central mechanisms of hypothalamo-pituitary-adrenal (HPA) counterregulatory responses...
Diabetes is associated with increased basal hypothalamo-pituitary-adrenal (HPA) activity and impaired stress responsiveness. Previously, we demonstrated that the HPA response to hypoglycemia significantly in diabetic rats. In this study our goals were 1) differentiate between effects of hyperinsulinemia those per se, 2) establish whether diabetes lowers peak responses. Normal streptozotocin-diabetic rats subjected hyperinsulinemic-euglycemic glucose clamps evaluate central peripheral These...
Deterioration of metabolic health is a hallmark aging and generally assumed to be detrimental longevity. Exposure high-calorie diet impairs metabolism accelerates aging; conversely, calorie restriction (CR) prevents age-related diseases extends lifespan. However, it unclear whether preservation sufficient extend We utilized genetic mouse model lacking Fabp4/5 that confers protection against shares molecular lipidomic features with CR address this question. Fabp-deficient mice exhibit...
Summary Mammalian tissues feed on nutrients in the blood circulation. At organism-level, mammalian energy metabolism comprises of oxidation, storage, interconverting, and releasing circulating nutrients. Though much is known about individual processes nutrients, a holistic quantitative model describing these for all major lacking. Here, by integrating isotope tracer infusion, mass spectrometry, gas analyzer measurement, we developed framework to systematically quantify fluxes through...
This study aimed to differentiate the effects of repeated antecedent hypoglycemia, marked hyperinsulinemia, and increases in corticosterone on counterregulation subsequent hypoglycemia normal rats. Specifically, we examined whether exposure hyperinsulinemia or elevated per se could impair counterregulation. Four groups male Sprague-Dawley rats were used: 1) controls (N) had 4 days sham treatment; 2) an group (AH) 7 episodes hyperinsulinemic over days; 3) (AE) euglycemia; 4) (AC) intravenous...