FGF21 Improves the Adipocyte Dysfunction Related to Seipin Deficiency
| العنوان: | FGF21 Improves the Adipocyte Dysfunction Related to Seipin Deficiency |
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| المؤلفون: | Audrey Ayer, Soazig Le Lay, Cédric Le May, Tamer Coskun, Xavier Prieur, Jocelyne Magré, L. Dollet, Quentin Venara, Ruth E. Gimeno, Bertrand Cariou, Clara Levrel, Andrew C. Adams |
| المساهمون: | unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Stress Oxydant et Pathologies Métaboliques (SOPAM), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN) |
| المصدر: | Diabetes Diabetes, 2016, Equipe 5, 65 (11), pp.3410--3417. ⟨10.2337/db16-0327⟩ Diabetes, American Diabetes Association, 2016, 65 (11), pp.3410-3417. ⟨10.2337/db16-0327⟩ |
| بيانات النشر: | HAL CCSD, 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | 0301 basic medicine, medicine.medical_specialty, FGF21, Endocrinology, Diabetes and Metabolism, [SDV]Life Sciences [q-bio], Adipocytes, White, Blotting, Western, White adipose tissue, Biology, Seipin, Mice, 03 medical and health sciences, chemistry.chemical_compound, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, 3T3-L1 Cells, GTP-Binding Protein gamma Subunits, Adipocyte, Internal medicine, Internal Medicine, medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Animals, Homeostasis, Adiponectin secretion, RNA, Messenger, ComputingMilieux_MISCELLANEOUS, Mice, Knockout, Gene knockdown, Adiponectin, Adipose tissue loss, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Heterotrimeric GTP-Binding Proteins, 3. Good health, Fibroblast Growth Factors, 030104 developmental biology, Endocrinology, Adipose Tissue, chemistry |
| الوصف: | International audience; Fibroblast growth factor 21 (FGF21) was shown to improve metabolic homeostasis, at least partly by controlling white adipocyte profile and adiponectin secretion. Here, we studied its effect on adipocyte dysfunction in the context of Berardinelli-Seip congenital lipodystrophy (BSCL) linked to seipin deficiency. Bscl2(-/-) mice displayed a progressive adipose tissue loss with aging as evidenced by the altered profile of residual fat pads and the decrease in adiponectin plasma levels in 12- vs. 4-week-old animals. Aiming to prevent this impairment, we treated 6-week-old Bscl2(-/-) mice with an FGF21 analog (LY2405319) for a period of 28 days. FGF21 treatment increased adiponectin plasma levels and normalized insulin sensitivity in Bscl2(-/-) mice by improving the white adipose tissue gene expression pattern. To further decipher the molecular pathways altered by seipin deficiency in mature adipocytes, we developed a unique inducible seipin knockdown cell line (SKD). SKD showed chronic activation of the p38 MAPK pathway associated with apoptotic cell death. Interestingly, FGF21 treatment exerted an antistress effect on SKD cells, reducing p38 MAPK phosphorylation and limiting mature adipocyte loss. Our data demonstrate that FGF21 treatment improves the metabolic profile of Bscl2(-/-) lipodystrophic mice, partly by improving mature adipocyte maintenance through suppression of cellular stress via inhibition of p38 MAPK activity. |
| اللغة: | English |
| تدمد: | 0012-1797 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::bc7641d61bcbaab81e84bf97c38a83bbTest https://hal.archives-ouvertes.fr/hal-01831750Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....bc7641d61bcbaab81e84bf97c38a83bb |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 00121797 |
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