scholarly journals Relative Adipose Tissue Failure in Alström Syndrome Drives Obesity-Induced Insulin Resistance

Diabetes ◽  
2020 ◽  
pp. db200647
Author(s):  
Tarekegn Geberhiwot ◽  
Shanat Baig ◽  
Cathy Obringer ◽  
Dorothée Girard ◽  
Charlotte Dawson ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Alström Syndrome ◽  
Alstrom Syndrome

scholarly journals Relative adipose tissue failure in Alström syndrome drives obesity-induced insulin resistance

2020 ◽  
Author(s):  
Ada Admin ◽  
Tarekegn Geberhiwot ◽  
Shanat Baig ◽  
Cathy Obringer ◽  
Dorothée Girard ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Therapeutic Strategies ◽  
Mice Model ◽  
Alström Syndrome ◽  
Monogenic Form ◽  
Depth Analysis ◽  
Alstrom Syndrome ◽  
Polygenic Obesity ◽  
First Time

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 hyperinsulinaemic-euglycemic clamping with concomitant adipose tissue (AT) microdialysis and an in-depth analysis of subcutaneous AT histology. We have shown a relative adipose tissue failure in monogenic obese cohort; a finding supported by observations in a novel conditional mouse model (<i>Alms<sup>flin/flin</sup></i>) and ALMS1-silenced human primary adipocytes. Whereas, selective reactivation of ALMS1 gene in adipose tissue of an ALMS conditional knockdown mice model (<i>Alms<sup>flin/flin</sup>;Adipo-Cre<sup>+/-</sup></i>) restores systemic insulin sensitivity and glucose tolerance. Hence, we show for the first time the relative adipose tissue failure in human obese cohorts to be a major determinant of accelerated IR without evidence of lipodystrophy. These new insights into adipocyte driven insulin resistance may assist development of adipose tissue targeted therapeutic strategies for diabetes.

scholarly journals Advanced non-alcoholic fatty liver disease and adipose tissue fibrosis in patients with Alström syndrome

2016 ◽  
Vol 36 (11) ◽  
pp. 1704-1712 ◽  
Author(s):  
Laura L. Gathercole ◽  
Jonathan M. Hazlehurst ◽  
Matthew J. Armstrong ◽  
Rachel Crowley ◽  
Sarah Boocock ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Alcoholic Fatty Liver ◽  
Tissue Fibrosis ◽  
Alström Syndrome ◽  
Alstrom Syndrome ◽  
Alcoholic Fatty Liver Disease

scholarly journals Alström syndrome: A rare association of retinitis pigmentosa with insulin resistance syndrome

2013 ◽  
Vol 17 (5) ◽  
pp. 949
Author(s):  
IrfanYousuf Wani ◽  
Ashraf Ganie ◽  
Iqra Mehraj ◽  
YasserYousuf Wani ◽  
Muzafar Naik
Keyword(s):  
Insulin Resistance ◽  
Retinitis Pigmentosa ◽  
Insulin Resistance Syndrome ◽  
Rare Association ◽  
Alström Syndrome ◽  
Alstrom Syndrome
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