A5037751053- Adipose Tissue and Metabolism
- Birth, Development, and Health
- Health, Medicine and Society
- Adipokines, Inflammation, and Metabolic Diseases
- Psychoanalysis and Psychopathology Research
- GDF15 and Related Biomarkers
- Nutrition and Health in Aging
- Social Policies and Family
- Nutrition, Genetics, and Disease
- Nuclear Structure and Function
- Palliative Care and End-of-Life Issues
- Aging, Elder Care, and Social Issues
- Healthcare Systems and Practices
- Macrophage Migration Inhibitory Factor
- Metabolism, Diabetes, and Cancer
- Diet and metabolism studies
- Family Support in Illness
- Pancreatic function and diabetes
- Endoplasmic Reticulum Stress and Disease
- Childhood Cancer Survivors' Quality of Life
- Lipoproteins and Cardiovascular Health
- Cancer-related cognitive impairment studies
- Mitochondrial Function and Pathology
- Stress Responses and Cortisol
- Hormonal Regulation and Hypertension
Pfizer (United States)
2012-2024
University of Pennsylvania
2023
Joslin Diabetes Center
2007-2018
Centre Jean Perrin
2006-2016
Harvard University
2007-2015
Centre Hospitalier Universitaire de Clermont-Ferrand
2000-2013
Hôpital Saint-Jacques
2013
Brigham and Women's Hospital
2010
Centre National de la Recherche Scientifique
2003-2005
Centre Antoine Lacassagne
2003
Obesity, diabetes, and metabolic syndrome result from complex interactions between genetic environmental factors, including the gut microbiota. To dissect these interactions, we utilized three commonly used inbred strains of mice—obesity/diabetes-prone C57Bl/6J mice, obesity/diabetes-resistant 129S1/SvImJ Jackson Laboratory, obesity-prone but diabetes-resistant 129S6/SvEvTac Taconic—plus derivative lines generated by breeding in a new, common environment. Analysis parameters microbiota all...
Mitochondrial dysfunction in adipose tissue occurs obesity, type 2 diabetes, and some forms of lipodystrophy, but whether this contributes to or is the result these disorders unknown. To investigate physiological consequences severe mitochondrial impairment tissue, we generated mice deficient transcription factor A (TFAM) adipocytes by using carrying adiponectin-Cre TFAM floxed alleles. These adiponectin TFAM-knockout (adipo-TFAM-KO) had a 75–81% reduction subcutaneous intra-abdominal white...
C57BL/6J and 129S6/Sv (B6 129) mice differ dramatically in their susceptibility to developing diabetes response diet- or genetically induced insulin resistance. A major locus contributing this difference has been mapped a region on mouse chromosome 14 that contains the gene encoding PKCδ. Here, we found PKCδ expression liver was 2-fold higher B6 versus 129 from birth further increased but not high-fat diet. PRKCD also elevated obese humans positively correlated with fasting glucose...
Exposure of preadipocytes to long-chain fatty acids induces the expression several markers adipocyte differentiation. In an attempt identify novel genes and proteins that are regulated by in preadipocytes, we performed a substractive hybridization screening identified PTX3, protein pentraxin family. PTX3 mRNA is transient during differentiation clonal cell lines absent fully differentiated cells. Stable overexpression has no effect on line with this, expressed stromal-vascular fraction...
Obesity, especially visceral obesity, is associated with insulin resistance and metabolic syndrome. We previously identified the cell surface proteoglycan glypican-4 as differentially expressed in subcutaneous versus white fat depots. Here we show that released from cells adipose tissue explants of mice, circulating levels correlate BMI sensitivity humans. Furthermore, interacts receptor, enhances receptor signaling, adipocyte differentiation. Conversely, depletion results reduced activation...
Increased intraabdominal (visceral) fat is associated with a high risk of diabetes and metabolic syndrome. We have previously shown that the mesodermal developmental transcription factor Tbx15 highly differentially expressed between visceral subcutaneous (s.c.) in both humans rodents, expression decreased obesity. Here we show that, mice, 260-fold more s.c. preadipocytes than epididymal preadipocytes. Overexpression 3T3-L1 impairs adipocyte differentiation decreases triglyceride content....
TRB3 has been implicated in the regulation of several biological processes mammalian cells through its ability to influence Akt and other signaling pathways. In this study, we investigated role regulating adipogenesis activity adipogenic transcription factors. We find that is expressed 3T3-L1 preadipocytes, expression transiently suppressed during initial days differentiation concomitant with induction C/EBPbeta. This event appears be a prerequisite for adipogenesis. Overexpression blocks at...
Cells lacking both insulin and IGF-1 receptors are resistant to apoptosis.
OBJECTIVE Type 2 diabetes and obesity are increasingly affecting human populations around the world. Our goal was to identify early molecular signatures predicting genetic risk these metabolic diseases using two strains of mice that differ greatly in disease susceptibility. RESEARCH DESIGN AND METHODS We integrated characterization, gene expression, protein-protein interaction networks, RT-PCR, flow cytometry analyses adipose, skeletal muscle, liver tissue diabetes-prone C57BL/6NTac (B6)...
Protein kinase C (PKC)δ has been shown to be increased in liver obesity and plays an important role the development of hepatic insulin resistance both mice humans. In current study, we explored PKCδ skeletal muscle control sensitivity glucose metabolism by generating which was deleted specifically using Cre-lox recombination. Deletion improved signaling young mice, especially at low doses; however, this did not change tolerance or tests done with pharmacological levels insulin. Likewise,...
Growth differentiation factor 15 (GDF15) causes anorexia and weight loss in animal models, higher circulating levels are associated with cachexia reduced survival cancer other chronic diseases such as sepsis. To investigate the role of sepsis-induced GDF15, we examined whether GDF15 neutralization via a validated highly potent monoclonal antibody, mAB2, modulates lipopolysaccharide (LPS)-induced anorexia, loss, mortality rodents. LPS injection transiently increased wild-type mice, decreased...
Abstract GDF15 is a distant TGF-β family member that induces anorexia and weight loss. Due to its function, has attracted attention as potential therapeutic for the treatment of obesity associated metabolic diseases. However, pharmacokinetic physicochemical properties present several challenges development therapeutic, including short half-life, high aggregation propensity, protease susceptibility in serum. Here, we report design, characterization optimization an Fc-fusion protein format...
Growth differentiation factor 15 (GDF15), a TGFβ superfamily cytokine, acts through its receptor, cell line-derived neurotrophic factorfamily receptor α-like (GFRAL), to suppress food intake and promote nausea. GDF15 is broadly expressed at low levels but increases in states of disease such as cancer, cachexia, sepsis. Whether necessary for inducing sepsis-associated anorexia body weight loss currently unclear. To test this we used model moderate systemic infection GDF15KO GFRALKO mice with...
Abstract Urocortin 2 (UCN2) acts as a ligand for the G protein-coupled receptor corticotropin-releasing hormone (CRHR2). UCN2 has been reported to improve or worsen insulin sensitivity and glucose tolerance in vivo. Here we show that acute dosing of induces systemic resistance male mice skeletal muscle. Inversely, chronic elevation by injection with adenovirus encoding resolves metabolic complications, improving tolerance. CRHR2 recruits Gs response low concentrations UCN2, well Gi...