title: Tenomodulin promotes human adipocyte differentiation and beneficial visceral adipose tissue expansion.
abstract: 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) is upregulated in adipose tissue of insulin-resistant versus insulin-sensitive individuals, who were matched for body mass index (BMI). TNMD expression increases in human preadipocytes during differentiation, whereas silencing TNMD blocks adipogenesis. Upon high-fat diet feeding, transgenic mice overexpressing Tnmd develop increased epididymal white adipose tissue (eWAT) mass, and preadipocytes derived from Tnmd transgenic mice display greater proliferation, consistent with elevated adipogenesis. In Tnmd transgenic mice, lipogenic genes are upregulated in eWAT, as is Ucp1 in brown fat, while liver triglyceride accumulation is attenuated. Despite expanded eWAT, transgenic animals display improved systemic insulin sensitivity, decreased collagen deposition and inflammation in eWAT, and increased insulin stimulation of Akt phosphorylation. Our data suggest that TNMD acts as a protective factor in visceral adipose tissue to alleviate insulin resistance in obesity.
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
authors.forename: Ozlem
authors.initials: O
authors.lastname: Senol-Cosar
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
authors.forename: Rachel J Roth
authors.initials: RJ
authors.lastname: Flach
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
authors.forename: Marina
authors.initials: M
authors.lastname: DiStefano
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
authors.forename: Anil
authors.initials: A
authors.lastname: Chawla
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Nicoloro
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
authors.forename: Juerg
authors.initials: J
authors.lastname: Straubhaar
authors.affiliation: Department of Internal Medicine, Touchstone Diabetes Center, The University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
authors.forename: Olga T
authors.initials: OT
authors.lastname: Hardy
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.|Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
authors.forename: Hye Lim
authors.initials: HL
authors.lastname: Noh
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.|Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
authors.forename: Jason K
authors.initials: JK
authors.lastname: Kim
authors.affiliation: Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm 89075, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Wabitsch
authors.affiliation: Department of Internal Medicine, Touchstone Diabetes Center, The University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
authors.forename: Philipp E
authors.identifier: http://orcid.org/0000-0003-0680-3392
authors.initials: PE
authors.lastname: Scherer
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Czech
mesh_terms: D017667:Adipocytes / Q000378:metabolism*; D002001:Adipose Tissue, Brown / Q000378:metabolism* / Q000473:pathology; D052436:Adipose Tissue, White / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000378:metabolism; D004822:Epididymis; D005260:Female; D005455:Fluorescent Antibody Technique; D015309:Glucose Clamp Technique; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D050152:Intra-Abdominal Fat / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D007473:Ion Channels / Q000378:metabolism*; D050155:Lipogenesis / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000378:metabolism*; D009767:Obesity, Morbid / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000378:metabolism; D000071256:Uncoupling Protein 1
chemical_list: D004268:DNA-Binding Proteins; D007473:Ion Channels; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; C521133:Prdm16 protein, mouse; C422444:TNMD protein, human; C486026:Tnmd protein, mouse; D014157:Transcription Factors; C000604371:UCP1 protein, human; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1; D051057:Proto-Oncogene Proteins c-akt