Carbon monoxide-induced metabolic switch in adipocytes improves insulin resistance in obese mice
Identifikátory výsledku
Kód výsledku v IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F18%3A10383532" target="_blank" >RIV/00216208:11110/18:10383532 - isvavai.cz</a>
Výsledek na webu
<a href="https://doi.org/10.1172/jci.insight.123485" target="_blank" >https://doi.org/10.1172/jci.insight.123485</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1172/jci.insight.123485" target="_blank" >10.1172/jci.insight.123485</a>
Alternativní jazyky
Jazyk výsledku
angličtina
Název v původním jazyce
Carbon monoxide-induced metabolic switch in adipocytes improves insulin resistance in obese mice
Popis výsledku v původním jazyce
Obesity is characterized by accumulation of adipose tissue and is one the most important risk factors in the development of insulin resistance. Carbon monoxide-releasing (CO-releasing) molecules (CO-RMs) have been reported to improve the metabolic profile of obese mice, but the underlying mechanism remains poorly defined. Here, we show that oral administration of CORM-401 to obese mice fed a high-fat diet (HFD) resulted in a significant reduction in body weight gain, accompanied by a marked improvement in glucose homeostasis. We further unmasked an action we believe to be novel, by which CO accumulates in visceral adipose tissue and uncouples mitochondrial respiration in adipocytes, ultimately leading to a concomitant switch toward glycolysis. This was accompanied by enhanced systemic and adipose tissue insulin sensitivity, as indicated by a lower blood glucose and increased Akt phosphorylation. Our findings indicate that the transient uncoupling activity of CO elicited by repetitive administration of CORM-401 is associated with lower weight gain and increased insulin sensitivity during HFD. Thus, prototypic compounds that release CO could be investigated for developing promising insulin-sensitizing agents.
Název v anglickém jazyce
Carbon monoxide-induced metabolic switch in adipocytes improves insulin resistance in obese mice
Popis výsledku anglicky
Obesity is characterized by accumulation of adipose tissue and is one the most important risk factors in the development of insulin resistance. Carbon monoxide-releasing (CO-releasing) molecules (CO-RMs) have been reported to improve the metabolic profile of obese mice, but the underlying mechanism remains poorly defined. Here, we show that oral administration of CORM-401 to obese mice fed a high-fat diet (HFD) resulted in a significant reduction in body weight gain, accompanied by a marked improvement in glucose homeostasis. We further unmasked an action we believe to be novel, by which CO accumulates in visceral adipose tissue and uncouples mitochondrial respiration in adipocytes, ultimately leading to a concomitant switch toward glycolysis. This was accompanied by enhanced systemic and adipose tissue insulin sensitivity, as indicated by a lower blood glucose and increased Akt phosphorylation. Our findings indicate that the transient uncoupling activity of CO elicited by repetitive administration of CORM-401 is associated with lower weight gain and increased insulin sensitivity during HFD. Thus, prototypic compounds that release CO could be investigated for developing promising insulin-sensitizing agents.
Klasifikace
Druh
J<sub>imp</sub> - Článek v periodiku v databázi Web of Science
CEP obor
—
OECD FORD obor
30202 - Endocrinology and metabolism (including diabetes, hormones)
Návaznosti výsledku
Projekt
—
Návaznosti
V - Vyzkumna aktivita podporovana z jinych verejnych zdroju
Ostatní
Rok uplatnění
2018
Kód důvěrnosti údajů
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Údaje specifické pro druh výsledku
Název periodika
JCI Insight [online]
ISSN
2379-3708
e-ISSN
—
Svazek periodika
3
Číslo periodika v rámci svazku
22
Stát vydavatele periodika
US - Spojené státy americké
Počet stran výsledku
14
Strana od-do
—
Kód UT WoS článku
000450338900011
EID výsledku v databázi Scopus
2-s2.0-85063243749