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

Carobbio, Stefania (författare)
Metabolic Research Laboratories, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom
Hagen, Rachel M. (författare)
Metabolic Research Laboratories, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom
Lelliott, Christopher J. (författare)
Department of Biosciences, CVGI IMED, AstraZeneca Research and Development, Mölndal, Sweden
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Slawik, Marc (författare)
Metabolic Research Laboratories, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom; Endocrine Research Unit, Medizinische Klinik-Innenstadt, Ludwig-Maximilians University, Munich, Germany
Medina-Gomez, Gema (författare)
Metabolic 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
Tan, Chong-Yew (författare)
Metabolic Research Laboratories, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom
Sicard, Audrey (författare)
Laboratory of Obesity, Institute of Metabolic and Cardiovascular Diseases (I2MC), Paul Sabatier University, Toulouse, France
Atherton, Helen J. (författare)
MRC Human Nutrition Research, Elsie Widdowson Laboratory, University of Cambridge, Cambridge, United Kingdom
Barbarroja, Nuria (författare)
Metabolic 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
Bjursell, Mikael (författare)
Department of Biosciences, CVGI IMED, AstraZeneca Research and Development, Mölndal, Sweden
Bohlooly-Y, Mohammad (författare)
Department of Biosciences, CVGI IMED, AstraZeneca Research and Development, Mölndal, Sweden
Virtue, Sam (författare)
Metabolic Research Laboratories, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom
Tuthill, Antoinette (författare)
Metabolic Research Laboratories, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom
Lefai, Etienne (författare)
Lyon CarMeN Laboratory, Human Nutrition Research Center, Lyon1 University, Lyon, France
Laville, Martine (författare)
Lyon CarMeN Laboratory, Human Nutrition Research Center, Lyon1 University, Lyon, France
Wu, Tingting (författare)
Department of Biosciences, CVGI IMED, AstraZeneca Research and Development, Mölndal, Sweden
Considine, Robert V. (författare)
Division of Endocrinology and Metabolism, School of Medicine, Indiana University, Indianapolis IN, United States
Vidal, Hubert (författare)
Lyon CarMeN Laboratory, Human Nutrition Research Center, Lyon1 University, Lyon, France
Langin, Dominique (författare)
Laboratory of Obesity, Institute of Metabolic and Cardiovascular Diseases (I2MC), Paul Sabatier University, Toulouse, France; Laboratory of Clinical Biochemistry, Toulouse, France
Oresic, Matej, 1967- (författare)
Örebro universitet,Institutionen för medicinska vetenskaper,Department of Medicine, Obesity Research Unit, Helsinki University Central Hospital, Helsinki, Finland
Tinahones, Francisco J. (författare)
Departamento de Bioquímica, Fisiología y Genética Molecular, Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos, Madrid, Spain
Fernandez-Real, Jose Manuel (författare)
Department of Diabetes, Endocrinology and Nutrition, Institut d'Investigació Biomédica de Girona, CIBERobn Fisiopatología de la Obesidad y Nutrición, Girona, Spain
Griffin, Julian L. (författare)
MRC Human Nutrition Research, Elsie Widdowson Laboratory, University of Cambridge, Cambridge, United Kingdom
Sethi, Jaswinder K. (författare)
Metabolic Research Laboratories, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom
López, Miguel (författare)
Metabolic 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
Vidal-Puig, Antonio (författare)
Metabolic Research Laboratories, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom; Wellcome Trust Sanger Institute, Hinxton, United Kingdom
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 (creator_code:org_t)
Cell Press, 2013
2013
Engelska.
Ingår i: ; 62:11, s. 3697-3708
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
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  • 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.

Ämnesord

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine (hsv//eng)

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