Adaptive Changes of the Insig1/SREBP1/SCD1 Set Point Help Adipose Tissue to Cope With Increased Storage Demands of Obesity
| العنوان: | Adaptive Changes of the Insig1/SREBP1/SCD1 Set Point Help Adipose Tissue to Cope With Increased Storage Demands of Obesity |
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| المؤلفون: | Hubert Vidal, Tingting Wu, Jaswinder K. Sethi, Martine Laville, Gema Medina-Gómez, Francisco J. Tinahones, Chong Yew Tan, Mikael Bjursell, Miguel López, Rachel M. Hagen, Antoinette Tuthill, Christopher J. Lelliott, Antonio Vidal-Puig, Helen J. Atherton, Julian L. Griffin, Audrey Sicard, Etienne Lefai, Matej Orešič, Mohammad Bohlooly-Y, Robert V. Considine, Sam Virtue, José Manuel Fernández-Real, Stefania Carobbio, Dominique Langin, Nuria Barbarroja, Marc Slawik |
| المساهمون: | ProdInra, Migration, University of Cambridge [UK] (CAM), AstraZeneca, Ludwig-Maximilians University [Munich] (LMU), Universidad Rey Juan Carlos [Madrid] (URJC), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Instituto de Salud Carlos III [Madrid] (ISC), Mécanisme Moléculaire du Diabète (MMD), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Indiana University, Indiana University System, Université Fédérale Toulouse Midi-Pyrénées, Laboratoire de Biochimie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Universidade de Santiago de Compostela [Spain] (USC ), The Wellcome Trust Sanger Institute [Cambridge], Lelliott, Christopher [0000-0001-8087-4530], Griffin, Julian [0000-0003-1336-7744], Vidal-Puig, Antonio [0000-0003-4220-9577], Apollo - University of Cambridge Repository, Ludwig Maximilians University of Munich, Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Laboratoire de biochimie clinique, CHU Toulouse [Toulouse], University of Helsinki |
| المصدر: | Diabetes RUNA. Repositorio da Consellería de Sanidade e Sergas Servizo Galego de Saúde (SERGAS) Diabetes, 2013, 62 (11), pp.3697-3708. ⟨10.2337/db12-1748⟩ Diabetes, American Diabetes Association, 2013, 62 (11), pp.3697-3708. ⟨10.2337/db12-1748⟩ |
| بيانات النشر: | American Diabetes Association, 2013. |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | [SDV]Life Sciences [q-bio], Endocrinology, Diabetes and Metabolism, Adipose tissue, chemistry.chemical_compound, Mice, sterol, 0302 clinical medicine, Adipocyte, element binding protein, 11 Medical and Health Sciences, Original Research, Mice, Knockout, 0303 health sciences, Adaptive response, Adaptation, Physiological, responsive gene, 3. Good health, Obesity, Morbid, [SDV] Life Sciences [q-bio], Endokrinologi och diabetes, Lipogenesis, lipids (amino acids, peptides, and proteins), Sterol Regulatory Element Binding Protein 1, Stearoyl-CoA Desaturase, medicine.medical_specialty, Adipose Tissue, White, Down-Regulation, 030209 endocrinology & metabolism, activated receptor gamma, Endocrinology and Diabetes, Biology, liver, 03 medical and health sciences, Endocrinology & Metabolism, Insulin resistance, Downregulation and upregulation, Internal medicine, Diabetes mellitus, 3T3-L1 Cells, Internal Medicine, medicine, Animals, Humans, Obesity, RNA, Messenger, fatty acid synthesis, 030304 developmental biology, Membrane Proteins, medicine.disease, Lipid Metabolism, Sterol regulatory element-binding protein, Endocrinology, Metabolism, chemistry, gene expression, identification, Insulin Resistance |
| الوصف: | 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. 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 |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1939-327X 0012-1797 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2f1b1c4a967559f56361109a5510ce68Test http://europepmc.org/articles/PMC3806615Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....2f1b1c4a967559f56361109a5510ce68 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1939327X 00121797 |
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