A5060003528- Adipose Tissue and Metabolism
- Adipokines, Inflammation, and Metabolic Diseases
- Metabolism, Diabetes, and Cancer
- Cytokine Signaling Pathways and Interactions
- Pancreatic function and diabetes
- Diet, Metabolism, and Disease
- Sirtuins and Resveratrol in Medicine
- Epigenetics and DNA Methylation
- Lipid metabolism and biosynthesis
- Retinoids in leukemia and cellular processes
- Fibroblast Growth Factor Research
- Peroxisome Proliferator-Activated Receptors
- Cardiovascular Disease and Adiposity
- Diet and metabolism studies
- Protein Tyrosine Phosphatases
- Mitochondrial Function and Pathology
- Exercise and Physiological Responses
- Kruppel-like factors research
- Muscle metabolism and nutrition
- Cancer, Hypoxia, and Metabolism
- Endoplasmic Reticulum Stress and Disease
- Growth Hormone and Insulin-like Growth Factors
- Regulation of Appetite and Obesity
- Chemokine receptors and signaling
- PI3K/AKT/mTOR signaling in cancer
Novo Nordisk Foundation
2017-2025
University of Copenhagen
2017-2025
Joslin Diabetes Center
2008-2014
Harvard University
2008-2012
Harvard University Press
2006-2010
Inserm
2000-2004
Walter and Eliza Hall Institute of Medical Research
2000
SOCS (suppressor of cytokine signaling) proteins are inhibitors signaling involved in negative feedback loops. We have recently shown that insulin increases SOCS-3 mRNA expression 3T3-L1 adipocytes. When expressed, binds to phosphorylated Tyr960 the receptor and prevents Stat 5B activation by insulin. Here we show COS-7 cells decreases insulin-induced substrate 1 (IRS-1) tyrosine phosphorylation its association with p85, a regulatory subunit phosphatidylinositol-3 kinase. This mechanism...
Sirt3 is a member of the sirtuin family protein deacetylases that localized in mitochondria and regulates mitochondrial function. expression skeletal muscle decreased models type 1 2 diabetes regulated by feeding, fasting, caloric restriction. knockout mice exhibit oxygen consumption develop oxidative stress muscle, leading to JNK activation impaired insulin signaling. This effect mimicked knockdown cultured myoblasts, which reduced oxidation, increased reactive species, JNK, serine tyrosine...
Obesity and body fat distribution are important risk factors for the development of type 2 diabetes metabolic syndrome. Evidence has accumulated that this is related to intrinsic differences in behavior adipocytes different depots. In current study, we demonstrate adipocyte precursor cells (APCs) isolated from visceral subcutaneous white adipose depots mice have distinct patterns gene expression, differentiation potential, response environmental genetic influences. APCs derived differentiate...
Environmental factors, such as the macronutrient composition of diet, can have a profound impact on risk diabetes and metabolic syndrome. In present study we demonstrate how single, simple dietary factor—leucine—can modify insulin resistance by acting multiple tissues at levels metabolism. Mice were placed normal or high fat diet (HFD). Dietary leucine was doubled addition to drinking water. mRNA, protein complete metabolomic profiles assessed in major sensitive serum, correlated with...
The hormone FGF21 regulates carbohydrate and lipid homeostasis as well body weight, increasing improves metabolic abnormalities associated with obesity diabetes. is thought to act on its target tissues, including liver adipose tissue, improve insulin sensitivity reduce adiposity. Here, we used mice selective hepatic inactivation of the IR (LIRKO) determine whether sensitization in mediates actions. Remarkably, hyperglycemia was completely normalized following treatment LIRKO mice, even...
Activation of energy expenditure in thermogenic fat is a promising strategy to improve metabolic health, yet the dynamic processes that evoke this response are poorly understood. Here we show synthesis mitochondrial phospholipid cardiolipin indispensable for stimulating and sustaining function. Cardiolipin biosynthesis robustly induced brown beige adipose upon cold exposure. Mimicking through overexpression synthase (Crls1) enhances consumption mouse human adipocytes. Crls1 deficiency...
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...
Human white adipocytes engineered to express UCP1 activate endogenous BAT and protect against diet-induced obesity when transplanted into mice.
Uncoupling protein-1 (UCP1) plays a central role in energy dissipation brown adipose tissue (BAT). Using high-throughput library screening of secreted peptides, we identify two fibroblast growth factors (FGF), FGF6 and FGF9, as potent inducers UCP1 expression adipocytes preadipocytes. Surprisingly, this occurs through mechanism independent adipogenesis involves FGF receptor-3 (FGFR3), prostaglandin-E2 interaction between estrogen receptor-related alpha, flightless-1 (FLII)...
Insulin resistance, a hallmark of type 2 diabetes and obesity, is associated with increased activity MAP stress-activated protein (SAP) kinases, which results in decreased insulin signaling. Our goal was to investigate the role kinase phosphatase-4 (MKP-4) modulating this process. We found that MKP-4 expression up-regulated during adipocyte myocyte differentiation vitro fasting white adipose tissue vivo. Overexpression 3T3-L1 cells inhibited ERK JNK phosphorylation and, lesser extent,...
Disturbed Wnt signaling has been implicated in numerous diseases, including type 2 diabetes and the metabolic syndrome. In present study, we have investigated cross-talk between insulin pathways using preadipocytes with without knockdown of co-receptors LRP5 LRP6 knock-out IGF-1 receptors. We find that stimulation leads to phosphorylation key mediators, Akt, GSK3β, ERK1/2, although a lower fold slower time course than observed for insulin. These effects are insulin/IGF-1 receptor-dependent...
Besides its thermogenic capacity, brown adipose tissue (BAT) performs important secretory functions that regulate metabolism. However, the BAT microenvironment and factors involved in homeostasis adaptation to cold remain poorly characterized. We therefore aimed study adipocyte-derived secreted may be adipocyte function and/or orchestrate intercellular communications. For this, mRNA levels mature adipocytes from mouse depots were assessed using RNA sequencing upon chronic acclimation,...
Both insulin and bone morphogenetic protein (BMP) signaling systems are important for adipocyte differentiation. Analysis of gene expression in BMP7-treated fibroblasts revealed a coordinated change components by BMP7. To further investigate the cross talk between BMP brown adipogenesis, we examined effect BMP7 receptor substrate 1 (IRS-1)-deficient preadipocytes, which exhibit severe defect Treatment these cells with 3 days prior to adipogenic induction restored differentiation markers. The...
Functional investigation of novel gene/protein targets associated with adipocyte differentiation or function heavily relies on efficient and accessible tools to manipulate gene expression in adipocytes vitro. Recent advances gene-editing technologies such as CRISPR-Cas9 have not only eased editing but also greatly facilitated modulation without altering the genome. Here, we aimed develop validate a competent vitro model controllable functionality well multiplexed manipulation adipocytes,...
Significance Aerobic exercise elicits an integrated metabolic response that involves multiple tissues and confers beneficial effects to health. Here we found this integrative energy-sensing pathways in muscle fat circulating factors lead the upregulation of type III endoribonuclease DICER adipose tissue consequent increase microRNAs. Upon upregulation, microRNA-203-3p inhibit glucose utilization by cells favor oxidative metabolism. In turn, supports exercised with adequate substrate...
Neurons in the arcuate nucleus of hypothalamus are involved regulation food intake and energy expenditure, dysregulation signalling these neurons promotes development obesity. The role rate-limiting enzyme NAD+ salvage pathway, nicotinamide phosphoribosyltransferase (NAMPT), for homeostasis by has not been extensively studied.We determined whether Nampt mRNA or protein levels mice were affected diet-induced obesity, fasting re-feeding, leptin ghrelin treatment. Primary hypothalamic treated...