دورية أكاديمية
Normal human adipose tissue functions and differentiation in patients with biallelic LPIN1 inactivating mutations
العنوان: | Normal human adipose tissue functions and differentiation in patients with biallelic LPIN1 inactivating mutations |
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المؤلفون: | Pelosi M., Testet E., Le Lay S., Dugail I., Tang X., Mabilleau G., Hamel Y., Madrange M., Blanc T., Odent T., McMullen T. P. W., Alfo' M., Brindley D. N., De Lonlay P. |
المساهمون: | Pelosi, M., Testet, E., Le Lay, S., Dugail, I., Tang, X., Mabilleau, G., Hamel, Y., Madrange, M., Blanc, T., Odent, T., Mcmullen, T. P. W., Alfo', M., Brindley, D. N., De Lonlay, P. |
بيانات النشر: | American Society for Biochemistry and Molecular Biology Inc. Bethesda |
سنة النشر: | 2017 |
المجموعة: | Sapienza Università di Roma: CINECA IRIS |
مصطلحات موضوعية: | adipocyte, adipogenic differentiation, gene expression, human fat lipid analysi, human lipid, Inborn errors of metabolism, lipodystrophie, phosphatases/lipid, adipose tissue, adolescent, allele, body fat distribution, body weight, case-control studie, cell differentiation, child, preschool, female, gene expression regulation, human, male, middle aged, PPAR gamma, peroxisome proliferator-activated receptor gamma coactivator 1-alpha, phosphatidate phosphatase, rhabdomyolysi, sterol regulatory element binding protein 1, mutation |
الوصف: | Lipin-1 is a Mg2+-dependent phosphatidic acid phosphatase (PAP) that in mice is necessary for normal glycerolipid biosynthesis, controlling adipocyte metabolism, and adipogenic differentiation. Mice carrying inactivating mutations in the Lpin1 gene display the characteristic features of human familial lipodystrophy. Very little is known about the roles of lipin-1 in human adipocyte physiology. Apparently, fat distribution and weight is normal in humans carrying LPIN1 inactivating mutations, but a detailed analysis of adipose tissue appearance and functions in these patients has not been available so far. In this study, we performed a systematic histopathological, biochemical, and gene expression analysis of adipose tissue biopsies from human patients harboring LPIN1 biallelic inactivating mutations and affected by recurrent episodes of severe rhabdomyolysis. We also explored the adipogenic differentiation potential of human mesenchymal cell populations derived from lipin-1 defective patients. White adipose tissue from human LPIN1 mutant patients displayed a dramatic decrease in lipin-1 protein levels and PAP activity, with a concomitant moderate reduction of adipocyte size. Nevertheless, the adipose tissue develops without obvious histological signs of lipodystrophy and with normal qualitative composition of storage lipids. The increased expression of key adipogenic determinants such as SREBP1, PPARG, and PGC1A shows that specific compensatory phenomena can be activated in vivo in human adipocytes with deficiency of functional lipin-1.—Pelosi, M., E. Testet, S. Le Lay, I. Dugail, X. Tang, G. Mabilleau, Y. Hamel, M. Madrange, T. Blanc, T. Odent, T. P. W. McMullen, M. Alfò, D. N. Brindley, and P. de Lonlay. Normal human adipose tissue functions and differentiation in patients with biallelic LPIN1 inactivating mutations. |
نوع الوثيقة: | article in journal/newspaper |
اللغة: | English |
العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/28986436; info:eu-repo/semantics/altIdentifier/wos/WOS:000416963900010; volume:58; issue:12; firstpage:2348; lastpage:2364; numberofpages:17; journal:JOURNAL OF LIPID RESEARCH; http://hdl.handle.net/11573/1553278Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85036582052 |
DOI: | 10.1194/jlr.P075440 |
الإتاحة: | https://doi.org/10.1194/jlr.P075440Test http://hdl.handle.net/11573/1553278Test |
حقوق: | info:eu-repo/semantics/openAccess |
رقم الانضمام: | edsbas.A0AB896 |
قاعدة البيانات: | BASE |
DOI: | 10.1194/jlr.P075440 |
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