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  • Carobbio, StefaniaMetabolic Research Laboratories, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom (author)

Adaptive changes of the Insig1/SREBP1/SCD1 set point help adipose tissue to cope with increased storage demands of obesity

  • Article/chapterEnglish2013

Publisher, publication year, extent ...

  • 2013-10-18
  • Cell Press,2013
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:oru-63685
  • https://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-63685URI
  • https://doi.org/10.2337/db12-1748DOI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • Funding agencies:MRC Biotechnology and Biological Sciences Research CouncilEuropean Foundation for the Study of DiabetesIntegrative Pharmacology FundFritz Thyssen Foundation fellowship (Germany)National Institute for Health Research
  • The epidemic of obesity imposes unprecedented challenges on human adipose tissue (WAT) storage capacity that may benefit from adaptive mechanisms to maintain adipocyte functionality. Here, we demonstrate that changes in the regulatory feedback set point control of Insig1/SREBP1 represent an adaptive response that preserves WAT lipid homeostasis in obese and insulin-resistant states. In our experiments, we show that Insig1 mRNA expression decreases in WAT from mice with obesity-associated insulin resistance and from morbidly obese humans and in in vitro models of adipocyte insulin resistance. Insig1 downregulation is part of an adaptive response that promotes the maintenance of SREBP1 maturation and facilitates lipogenesis and availability of appropriate levels of fatty acid unsaturation, partially compensating the antilipogenic effect associated with insulin resistance. We describe for the first time the existence of this adaptive mechanism in WAT, which involves Insig1/SREBP1 and preserves the degree of lipid unsaturation under conditions of obesity-induced insulin resistance. These adaptive mechanisms contribute to maintain lipid desaturation through preferential SCD1 regulation and facilitate fat storage in WAT, despite on-going metabolic stress.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Hagen, Rachel M.Metabolic Research Laboratories, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom (author)
  • Lelliott, Christopher J.Department of Biosciences, CVGI IMED, AstraZeneca Research and Development, Mölndal, Sweden (author)
  • Slawik, MarcMetabolic Research Laboratories, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom; Endocrine Research Unit, Medizinische Klinik-Innenstadt, Ludwig-Maximilians University, Munich, Germany (author)
  • Medina-Gomez, GemaMetabolic Research Laboratories, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom; Departamento de Bioquímica, Fisiología y Genética Molecular, Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos, , Madrid, Spain (author)
  • Tan, Chong-YewMetabolic Research Laboratories, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom (author)
  • Sicard, AudreyLaboratory of Obesity, Institute of Metabolic and Cardiovascular Diseases (I2MC), Paul Sabatier University, Toulouse, France (author)
  • Atherton, Helen J.MRC Human Nutrition Research, Elsie Widdowson Laboratory, University of Cambridge, Cambridge, United Kingdom (author)
  • Barbarroja, NuriaMetabolic Research Laboratories, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom; Hospital Virgen de la Victoria, CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Malaga, Spain (author)
  • Bjursell, MikaelDepartment of Biosciences, CVGI IMED, AstraZeneca Research and Development, Mölndal, Sweden (author)
  • Bohlooly-Y, MohammadDepartment of Biosciences, CVGI IMED, AstraZeneca Research and Development, Mölndal, Sweden (author)
  • Virtue, SamMetabolic Research Laboratories, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom (author)
  • Tuthill, AntoinetteMetabolic Research Laboratories, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom (author)
  • Lefai, EtienneLyon CarMeN Laboratory, Human Nutrition Research Center, Lyon1 University, Lyon, France (author)
  • Laville, MartineLyon CarMeN Laboratory, Human Nutrition Research Center, Lyon1 University, Lyon, France (author)
  • Wu, TingtingDepartment of Biosciences, CVGI IMED, AstraZeneca Research and Development, Mölndal, Sweden (author)
  • Considine, Robert V.Division of Endocrinology and Metabolism, School of Medicine, Indiana University, Indianapolis IN, United States (author)
  • Vidal, HubertLyon CarMeN Laboratory, Human Nutrition Research Center, Lyon1 University, Lyon, France (author)
  • Langin, DominiqueLaboratory of Obesity, Institute of Metabolic and Cardiovascular Diseases (I2MC), Paul Sabatier University, Toulouse, France; Laboratory of Clinical Biochemistry, Toulouse, France (author)
  • Oresic, Matej,1967-Örebro universitet,Institutionen för medicinska vetenskaper,Department of Medicine, Obesity Research Unit, Helsinki University Central Hospital, Helsinki, Finland(Swepub:oru)moc (author)
  • Tinahones, Francisco J.Departamento de Bioquímica, Fisiología y Genética Molecular, Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos, Madrid, Spain (author)
  • Fernandez-Real, Jose ManuelDepartment of Diabetes, Endocrinology and Nutrition, Institut d'Investigació Biomédica de Girona, CIBERobn Fisiopatología de la Obesidad y Nutrición, Girona, Spain (author)
  • Griffin, Julian L.MRC Human Nutrition Research, Elsie Widdowson Laboratory, University of Cambridge, Cambridge, United Kingdom (author)
  • Sethi, Jaswinder K.Metabolic Research Laboratories, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom (author)
  • López, MiguelMetabolic Research Laboratories, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom; Department of Physiology, CIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, Spain (author)
  • Vidal-Puig, AntonioMetabolic Research Laboratories, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom; Wellcome Trust Sanger Institute, Hinxton, United Kingdom (author)
  • Metabolic Research Laboratories, Addenbrooke's Hospital, University of Cambridge, Cambridge, United KingdomDepartment of Biosciences, CVGI IMED, AstraZeneca Research and Development, Mölndal, Sweden (creator_code:org_t)

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  • In:Diabetes: Cell Press62:11, s. 3697-37080012-17971939-327X

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