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Human White Adipose Tissue Displays Selective Insulin Resistance in the Obese State
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posted on 2021-04-16, 17:37 authored by Enrichetta Mileti, Kelvin HM. Kwok, Daniel P. Andersson, Anthony Mathelier, Amitha Raman, Jesper Bäckdahl, Jutta Jalkanen, Lucas Massier, Anders Thorell, Hui Gao, Peter Arner, Niklas Mejhert, Carsten O. Daub, Mikael RydénSelective
hepatic insulin resistance is a feature of obesity and type 2 diabetes. Whether
similar mechanisms operate in white adipose tissue (WAT) of obese subjects and
to what extent these are normalized by weight loss is unknown. We determined
insulin sensitivity by hyperinsulinemic euglycemic clamp and the insulin
response in subcutaneous WAT by RNA-sequencing in 23 women with obesity before
and two years after bariatric surgery. To control for effects of surgery, women
post-surgery were matched to never-obese subjects. Multidimensional analyses of
138 samples allowed us to classify the effects of insulin into three distinct
expression responses: a common set was present in all three groups and
included genes encoding several lipid/cholesterol biosynthesis enzymes; a set of
obesity-attenuated genes linked to tissue remodelling and protein
translation was selectively regulated in the two non-obese states and several post
obesity-enriched genes encoding proteins involved in e.g. one carbon
metabolism were only responsive to insulin in the women who had lost weight. Altogether,
human WAT displays a selective insulin response in the obese state where
most genes are normalized by weight loss. This comprehensive atlas provides insights
into the transcriptional effects of insulin in WAT and may identify targets to improve insulin action.