TRAIL (TNF-related apoptosis-inducing ligand) regulates adipocyte metabolism by caspase-mediated cleavage of PPARgamma. 2013

M Keuper, and I Wernstedt Asterholm, and P E Scherer, and M-A Westhoff, and P Möller, and K-M Debatin, and G Strauss, and M Wabitsch, and P Fischer-Posovszky
Division of Pediatric Endocrinology, Diabetes and Obesity Unit, Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany.

Tumor necrosis factor α (TNFα) and other members of the TNF family affect adipose tissue metabolism and contribute to the obesity-related inflammation of adipose tissue. Here, we sought to identify the effects of TRAIL (TNF-related apoptosis-inducing ligand) on fat cell biology. TRAIL-receptor 2 (TRAIL-R2) and its mouse homolog DR5 were regulated upon acute and chronic energy imbalance in murine and human adipose tissue. TRAIL inhibited insulin-stimulated glucose uptake and de novo lipogenesis in human adipocytes. Interestingly, TRAIL did not interfere with the phosphorylation of insulin-stimulated kinases such as Akt or Erk and did not activate the NF-κB pathway. Instead, TRAIL activated cleavage of caspase-8 and caspase-3. The subsequent cleavage of PPARγ led to its inactivation and resulted in reduced expression of lipogenic genes, such as Glut-4, FASN, and ACC. Taken together, we discovered a so far unknown function of the death ligand TRAIL in regulating adipocyte metabolism. Our results imply that TRAIL/TRAIL-R system might provide a new target for the prevention and treatment of obesity and its co-morbidities.

UI MeSH Term Description Entries
D007328 Insulin A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1). Iletin,Insulin A Chain,Insulin B Chain,Insulin, Regular,Novolin,Sodium Insulin,Soluble Insulin,Chain, Insulin B,Insulin, Sodium,Insulin, Soluble,Regular Insulin
D010766 Phosphorylation The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. Phosphorylations
D011994 Recombinant Proteins Proteins prepared by recombinant DNA technology. Biosynthetic Protein,Biosynthetic Proteins,DNA Recombinant Proteins,Recombinant Protein,Proteins, Biosynthetic,Proteins, Recombinant DNA,DNA Proteins, Recombinant,Protein, Biosynthetic,Protein, Recombinant,Proteins, DNA Recombinant,Proteins, Recombinant,Recombinant DNA Proteins,Recombinant Proteins, DNA
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D005947 Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Dextrose,Anhydrous Dextrose,D-Glucose,Glucose Monohydrate,Glucose, (DL)-Isomer,Glucose, (alpha-D)-Isomer,Glucose, (beta-D)-Isomer,D Glucose,Dextrose, Anhydrous,Monohydrate, Glucose
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D016328 NF-kappa B Ubiquitous, inducible, nuclear transcriptional activator that binds to enhancer elements in many different cell types and is activated by pathogenic stimuli. The NF-kappa B complex is a heterodimer composed of two DNA-binding subunits: NF-kappa B1 and relA. Immunoglobulin Enhancer-Binding Protein,NF-kappa B Complex,Nuclear Factor kappa B,Transcription Factor NF-kB,kappa B Enhancer Binding Protein,Ig-EBP-1,NF-kB,NF-kappaB,Nuclear Factor-Kappab,Complex, NF-kappa B,Enhancer-Binding Protein, Immunoglobulin,Factor NF-kB, Transcription,Factor-Kappab, Nuclear,Ig EBP 1,Immunoglobulin Enhancer Binding Protein,NF kB,NF kappa B Complex,NF kappaB,NF-kB, Transcription Factor,Nuclear Factor Kappab,Transcription Factor NF kB
D017209 Apoptosis A regulated cell death mechanism characterized by distinctive morphologic changes in the nucleus and cytoplasm, including the endonucleolytic cleavage of genomic DNA, at regularly spaced, internucleosomal sites, i.e., DNA FRAGMENTATION. It is genetically programmed and serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. Apoptosis, Extrinsic Pathway,Apoptosis, Intrinsic Pathway,Caspase-Dependent Apoptosis,Classic Apoptosis,Classical Apoptosis,Programmed Cell Death,Programmed Cell Death, Type I,Apoptoses, Extrinsic Pathway,Apoptoses, Intrinsic Pathway,Apoptosis, Caspase-Dependent,Apoptosis, Classic,Apoptosis, Classical,Caspase Dependent Apoptosis,Cell Death, Programmed,Classic Apoptoses,Extrinsic Pathway Apoptoses,Extrinsic Pathway Apoptosis,Intrinsic Pathway Apoptoses,Intrinsic Pathway Apoptosis
D017667 Adipocytes Cells in the body that store FATS, usually in the form of TRIGLYCERIDES. WHITE ADIPOCYTES are the predominant type and found mostly in the abdominal cavity and subcutaneous tissue. BROWN ADIPOCYTES are thermogenic cells that can be found in newborns of some species and hibernating mammals. Fat Cells,Lipocytes,Adipocyte,Cell, Fat,Cells, Fat,Fat Cell,Lipocyte

Related Publications

M Keuper, and I Wernstedt Asterholm, and P E Scherer, and M-A Westhoff, and P Möller, and K-M Debatin, and G Strauss, and M Wabitsch, and P Fischer-Posovszky
October 2016, Cell death & disease,
M Keuper, and I Wernstedt Asterholm, and P E Scherer, and M-A Westhoff, and P Möller, and K-M Debatin, and G Strauss, and M Wabitsch, and P Fischer-Posovszky
February 2014, Clinical endocrinology,
M Keuper, and I Wernstedt Asterholm, and P E Scherer, and M-A Westhoff, and P Möller, and K-M Debatin, and G Strauss, and M Wabitsch, and P Fischer-Posovszky
October 2002, Cellular immunology,
M Keuper, and I Wernstedt Asterholm, and P E Scherer, and M-A Westhoff, and P Möller, and K-M Debatin, and G Strauss, and M Wabitsch, and P Fischer-Posovszky
November 2011, Journal of leukocyte biology,
M Keuper, and I Wernstedt Asterholm, and P E Scherer, and M-A Westhoff, and P Möller, and K-M Debatin, and G Strauss, and M Wabitsch, and P Fischer-Posovszky
January 2011, Experimental cell research,
M Keuper, and I Wernstedt Asterholm, and P E Scherer, and M-A Westhoff, and P Möller, and K-M Debatin, and G Strauss, and M Wabitsch, and P Fischer-Posovszky
March 2003, Journal of medical and dental sciences,
M Keuper, and I Wernstedt Asterholm, and P E Scherer, and M-A Westhoff, and P Möller, and K-M Debatin, and G Strauss, and M Wabitsch, and P Fischer-Posovszky
September 2004, Experimental hematology,
M Keuper, and I Wernstedt Asterholm, and P E Scherer, and M-A Westhoff, and P Möller, and K-M Debatin, and G Strauss, and M Wabitsch, and P Fischer-Posovszky
December 1997, British journal of haematology,
M Keuper, and I Wernstedt Asterholm, and P E Scherer, and M-A Westhoff, and P Möller, and K-M Debatin, and G Strauss, and M Wabitsch, and P Fischer-Posovszky
January 2015, Iranian journal of pharmaceutical research : IJPR,
M Keuper, and I Wernstedt Asterholm, and P E Scherer, and M-A Westhoff, and P Möller, and K-M Debatin, and G Strauss, and M Wabitsch, and P Fischer-Posovszky
May 2014, Clinical and experimental medicine,
Copied contents to your clipboard!