Geberhiwot, Tarekegn, Baig, Shanat, Obringer, Cathy, Girard, Dorothée, Dawson, Charlotte, Manolopoulos, Konstantinos, Messaddeq, Nadia, Bel Lassen, Pierre, Clement, Karine, Tomlinson, Jeremy W, Steeds, Richard Paul, Dollfus, Hélène, Petrovsky, Nikolai and Marion, Vincent (2021) Relative Adipose Tissue Failure in Alström Syndrome Drives Obesity-Induced Insulin Resistance. Diabetes, 70 (2). pp. 364-376. ISSN 1939-327X. This article is available to all UHB staff and students login using a UHB Athens Account. Register for Athens here - https://openathens.nice.org.uk/
Full text not available from this repository.Abstract
Obesity is a major risk factor for insulin resistance (IR) and its attendant complications. The pathogenic mechanisms linking them remain poorly understood, partly due to a lack of intermediary monogenic human phenotypes. Here, we report on a monogenic form of IR-prone obesity, Alström syndrome (ALMS). Twenty-three subjects with monogenic or polygenic obesity underwent hyperinsulinemic-euglycemic clamping with concomitant adipose tissue (AT) microdialysis and an in-depth analysis of subcutaneous AT histology. We have shown a relative AT failure in a monogenic obese cohort, a finding supported by observations in a novel conditional mouse model ( ) and ALMS1-silenced human primary adipocytes, whereas selective reactivation of ALMS1 gene in AT of an ALMS conditional knockdown mouse model ( ) restores systemic insulin sensitivity and glucose tolerance. Hence, we show for the first time the relative AT failure in human obese cohorts to be a major determinant of accelerated IR without evidence of lipodystrophy. These new insights into adipocyte-driven IR may assist development of AT-targeted therapeutic strategies for diabetes.
Item Type: | Article |
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Additional Information: | This article is available to all UHB staff and students login using a UHB Athens Account. Register for Athens here - https://openathens.nice.org.uk/ |
Subjects: | WD Diseases and disorders of systemic, metabolic or environmental origin WD Diseases and disorders of systemic, metabolic or environmental origin > WD250 Metabolic diseases WG Cardiovascular system. Cardiology WK Endocrine system. Endocrinology |
Divisions: | Ambulatory Care > Diabetes |
Related URLs: | |
Depositing User: | Jamie Edgar |
Date Deposited: | 17 May 2021 12:34 |
Last Modified: | 05 May 2022 07:26 |
URI: | http://www.repository.uhblibrary.co.uk/id/eprint/4324 |
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