Downregulation of the Glo1 Gene Is Associated with Reduced Adiposity and Ectopic Fat Accumulation in Spontaneously Hypertensive Rats

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985823%3A_____%2F20%3A00535655" target="_blank" >RIV/67985823:_____/20:00535655 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11110/20:10419717 RIV/00216208:11310/20:10419717 RIV/00023001:_____/20:00080552 RIV/00064165:_____/20:10419717

Výsledek na webu

<a href="https://www.mdpi.com/2076-3921/9/12/1179" target="_blank" >https://www.mdpi.com/2076-3921/9/12/1179</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/antiox9121179" target="_blank" >10.3390/antiox9121179</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Downregulation of the Glo1 Gene Is Associated with Reduced Adiposity and Ectopic Fat Accumulation in Spontaneously Hypertensive Rats

Popis výsledku v původním jazyce

Methylglyoxal (MG), a potent precursor of advanced glycation end-products (AGE), is increased in metabolic disorders such as diabetes and obesity. MG and other dicarbonyl metabolites are detoxified by the glyoxalase system in which glyoxalase 1, coded by the Glo1 gene, serves as the rate-limiting enzyme. In this study, we analyzed the effects of Glo1 downregulation on glucose and lipid metabolism parameters in spontaneously hypertensive rats (SHR) by targeting the Glo1 gene (SHR-Glo1+/− heterozygotes). Compared to SHR wild-type animals, SHR-Glo1+/− rats showed significantly reduced Glo1 expression and lower GLO1 activity in tissues associated with increased MG levels. In contrast to SHR controls, SHR-Glo1+/− rats exhibited lower relative weight of epididymal fat, reduced ectopic fat accumulation in the liver and heart, and decreased serum triglycerides. In addition, compared to controls, SHR-Glo1+/− rats showed reduced serum insulin and increased basal and insulin stimulated incorporation of glucose into white adipose tissue lipids (lipogenesis). Reduced ectopic fat accumulation in the heart was associated with significantly increased pAMPK/AMPK ratio and GLUT4 activity. These results provide evidence that Glo1 downregulation in SHR is associated with reduced adiposity and ectopic fat accumulation, most likely mediated by AMPK activation in the heart.

Název v anglickém jazyce

Downregulation of the Glo1 Gene Is Associated with Reduced Adiposity and Ectopic Fat Accumulation in Spontaneously Hypertensive Rats

Popis výsledku anglicky

Methylglyoxal (MG), a potent precursor of advanced glycation end-products (AGE), is increased in metabolic disorders such as diabetes and obesity. MG and other dicarbonyl metabolites are detoxified by the glyoxalase system in which glyoxalase 1, coded by the Glo1 gene, serves as the rate-limiting enzyme. In this study, we analyzed the effects of Glo1 downregulation on glucose and lipid metabolism parameters in spontaneously hypertensive rats (SHR) by targeting the Glo1 gene (SHR-Glo1+/− heterozygotes). Compared to SHR wild-type animals, SHR-Glo1+/− rats showed significantly reduced Glo1 expression and lower GLO1 activity in tissues associated with increased MG levels. In contrast to SHR controls, SHR-Glo1+/− rats exhibited lower relative weight of epididymal fat, reduced ectopic fat accumulation in the liver and heart, and decreased serum triglycerides. In addition, compared to controls, SHR-Glo1+/− rats showed reduced serum insulin and increased basal and insulin stimulated incorporation of glucose into white adipose tissue lipids (lipogenesis). Reduced ectopic fat accumulation in the heart was associated with significantly increased pAMPK/AMPK ratio and GLUT4 activity. These results provide evidence that Glo1 downregulation in SHR is associated with reduced adiposity and ectopic fat accumulation, most likely mediated by AMPK activation in the heart.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30201 - Cardiac and Cardiovascular systems

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2020

Kód důvěrnosti údajů

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

Název periodika

ANTIOXIDANTS

ISSN

2076-3921

e-ISSN

—

Svazek periodika

9

Číslo periodika v rámci svazku

12

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

14

Strana od-do

1179

Kód UT WoS článku

000601827500001

EID výsledku v databázi Scopus

2-s2.0-85096861578