Inhibition of Lipolysis With Acipimox Attenuates Postburn White Adipose Tissue Browning and Hepatic Fat Infiltration.
Adipose Tissue
/ drug effects
Adipose Tissue, White
/ drug effects
Animals
Blotting, Western
Burns
/ metabolism
Fatty Acids, Nonesterified
/ metabolism
Immunohistochemistry
Lipolysis
/ drug effects
Liver
/ drug effects
Male
Mice
Mice, Inbred C57BL
Pyrazines
/ pharmacology
Sterol Esterase
/ metabolism
Weight Loss
/ drug effects
Journal
Shock (Augusta, Ga.)
ISSN: 1540-0514
Titre abrégé: Shock
Pays: United States
ID NLM: 9421564
Informations de publication
Date de publication:
02 2020
02 2020
Historique:
pubmed:
20
8
2019
medline:
2
2
2021
entrez:
20
8
2019
Statut:
ppublish
Résumé
Extensive burn injuries promote an increase in the lipolysis of white adipose tissue (WAT), a complication that enhances postburn hypermetabolism contributing to hyperlipidemia and hepatic steatosis. The systemic increase of free fatty acids (FFAs) due to burn-induced lipolysis and subsequent organ fatty infiltration may culminate in multiple organ dysfunction and, ultimately, death. Thus, reducing WAT lipolysis to diminish the mobilization of FFAs may render an effective means to improve outcomes postburn. Here, we investigated the metabolic effects of Acipimox, a clinically approved drug that suppresses lipolysis via inhibition of hormone-sensitive lipase (HSL). Using a murine model of thermal injury, we show that specific inhibition of HSL with Acipimox effectively suppresses burn-induced lipolysis in the inguinal WAT leading to lower levels of circulating FFAs at 7 days postburn (P < 0.05). The FFA substrate shortage indirectly repressed the thermogenic activation of adipose tissue after injury, reflected by the decrease in protein expression of key browning markers, UCP-1 (P < 0.001) and PGC-1α (P < 0.01). Importantly, reduction of FFA mobilization by Acipimox significantly decreased liver weight and intracellular fat accumulation (P < 0.05), suggesting that it may also improve organ function postburn. Our data validate the pharmacological inhibition of lipolysis as a potentially powerful therapeutic strategy to counteract the detrimental metabolic effects induced by burn.
Identifiants
pubmed: 31425403
doi: 10.1097/SHK.0000000000001439
pii: 00024382-202002000-00002
doi:
Substances chimiques
Fatty Acids, Nonesterified
0
Pyrazines
0
Sterol Esterase
EC 3.1.1.13
acipimox
K9AY9IR2SD
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
137-145Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM087285
Pays : United States
Organisme : CIHR
ID : 123336
Pays : Canada
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