Relative Adipose Tissue Failure in Alstrom Syndrome Drives Obesity-Induced Insulin Resistance.

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 (Alms ^flin/flin ) and ALMS1-silenced human primary adipocytes, whereas selective reactivation of ALMS1 gene in AT of an ALMS

SUBMITTER: Geberhiwot T 

PROVIDER: S-EPMC7881858 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature