Inhibition of Lipolysis With Acipimox Attenuates Postburn White Adipose Tissue Browning and Hepatic Fat Infiltration

被引:18
|
作者
Barayan, Dalia [4 ]
Vinaik, Roohi [4 ]
Auger, Christopher [2 ,3 ]
Knuth, Carly M. [4 ]
Abdullahi, Abdikarim [2 ,3 ]
Jeschke, Marc G. [1 ,2 ,3 ,4 ]
机构
[1] Univ Toronto, Dept Surg, Div Plast Surg, Toronto, ON, Canada
[2] Sunnybrook Hlth Sci Ctr, Ross Tilley Burn Ctr, 2075 Bayview Ave,Rm D704, Toronto, ON M4N 3M5, Canada
[3] Sunnybrook Res Inst, 2075 Bayview Ave,Rm D704, Toronto, ON M4N 3M5, Canada
[4] Univ Toronto, Inst Med Sci, Toronto, ON, Canada
来源
SHOCK | 2020年 / 53卷 / 02期
基金
美国国家卫生研究院; 加拿大健康研究院; 加拿大创新基金会;
关键词
Adipose tissue; hormone sensitive lipase; lipogenesis; liver; thermal injury; thermogenesis; HORMONE-SENSITIVE LIPASE; INSULIN-RESISTANCE; ACID OXIDATION; MICE; INFLAMMATION; DEFICIENCY; MECHANISM; MUSCLE; DIET;
D O I
10.1097/SHK.0000000000001439
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
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-1 alpha (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.
引用
收藏
页码:137 / 145
页数:9
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