Interaction between hormone-sensitive lipase and ChREBP in fat cells controls insulin sensitivity

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11120%2F19%3A43919417" target="_blank" >RIV/00216208:11120/19:43919417 - isvavai.cz</a>

Výsledek na webu

<a href="https://doi.org/10.1038/s42255-018-0007-6" target="_blank" >https://doi.org/10.1038/s42255-018-0007-6</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s42255-018-0007-6" target="_blank" >10.1038/s42255-018-0007-6</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Interaction between hormone-sensitive lipase and ChREBP in fat cells controls insulin sensitivity

Popis výsledku v původním jazyce

Impaired adipose tissue insulin signalling is a critical feature of insulin resistance. Here we identify a pathway linking the lipolytic enzyme hormone-sensitive lipase (HSL) to insulin action via the glucose-responsive transcription factor ChREBP and its target, the fatty acid elongase ELOVL6. Genetic inhibition of HSL in human adipocytes and mouse adipose tissue results in enhanced insulin sensitivity and induction of ELOVL6. ELOVL6 promotes an increase in phospholipid oleic acid, which modifies plasma membrane fluidity and enhances insulin signalling. HSL deficiency-mediated effects are suppressed by gene silencing of ChREBP and ELOVL6. Mechanistically, physical interaction between HSL, independent of lipase activity, and the isoform activated by glucose metabolism ChREBP alpha impairs ChREBP alpha translocation into the nucleus and induction of ChREBP beta, the isoform with high transcriptional activity that is strongly associated with whole-body insulin sensitivity. Targeting the HSL-ChREBP interaction may allow therapeutic strategies for the restoration of insulin sensitivity.

Název v anglickém jazyce

Interaction between hormone-sensitive lipase and ChREBP in fat cells controls insulin sensitivity

Popis výsledku anglicky

Impaired adipose tissue insulin signalling is a critical feature of insulin resistance. Here we identify a pathway linking the lipolytic enzyme hormone-sensitive lipase (HSL) to insulin action via the glucose-responsive transcription factor ChREBP and its target, the fatty acid elongase ELOVL6. Genetic inhibition of HSL in human adipocytes and mouse adipose tissue results in enhanced insulin sensitivity and induction of ELOVL6. ELOVL6 promotes an increase in phospholipid oleic acid, which modifies plasma membrane fluidity and enhances insulin signalling. HSL deficiency-mediated effects are suppressed by gene silencing of ChREBP and ELOVL6. Mechanistically, physical interaction between HSL, independent of lipase activity, and the isoform activated by glucose metabolism ChREBP alpha impairs ChREBP alpha translocation into the nucleus and induction of ChREBP beta, the isoform with high transcriptional activity that is strongly associated with whole-body insulin sensitivity. Targeting the HSL-ChREBP interaction may allow therapeutic strategies for the restoration of insulin sensitivity.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30202 - Endocrinology and metabolism (including diabetes, hormones)

Projekt

—

Návaznosti

N - Vyzkumna aktivita podporovana z neverejnych zdroju

Rok uplatnění

2019

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Nature Metabolism

ISSN

2522-5812

e-ISSN

—

Svazek periodika

1

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

14

Strana od-do

133-146

Kód UT WoS článku

000500725600017

EID výsledku v databázi Scopus

2-s2.0-85058842115