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Hemistepsin A inhibits T0901317-induced lipogenesis in the liver

BMB Reports 2021년 54권 2호 p.106 ~ 111
김재광, 조일제, 김은옥, Lee Dae-Geon, 정대화, 기성환, 구새광, 김상찬,
소속 상세정보
김재광 ( Kim Jae-Kwang ) - Daegu Haany University College of Korean Medicine
조일제 ( Cho Il-Je ) - Daegu Haany University College of Korean Medicine
김은옥 ( Kim Eun-Ok ) - Daegu Haany University College of Korean Medicine
 ( Lee Dae-Geon ) - Daegu Haany University College of Korean Medicine
정대화 ( Jung Dae-Hwa ) - Daegu Haany University College of Korean Medicine
기성환 ( Ki Sung-Hwan ) - Chosun University College of Pharmacy
구새광 ( Ku Sae-Kwang ) - Daegu Haany University College of Korean Medicine
김상찬 ( Kim Sang-Chan ) - Daegu Haany University College of Korean Medicine

Abstract


Hemistepsin A (HsA) is a guaianolide sesquiterpene lactone that inhibits hepatitis and liver fibrosis. We evaluated the effects of HsA on liver X receptor (LXR)-mediated hepatic lipogenesis in vitro and in vivo. Up to 10 μM, HsA did not affect the viability of HepG2 and Huh7 cells. Pretreatment with 5-10 μM HsA significantly decreased the luciferase activity of the LXR response element, which was transactivated by T0901317, GW 3965, and LXRα/retinoid X receptor α overexpression. In addition, it significantly inhibited the mRNA expression of LXRα in HepG2 and Huh7 cells. It also suppressed the expression of sterol regulatory element-binding protein-1c and lipogenic genes and reduced the triglyceride accumulation triggered by T0901317. Intraperitoneal injection of HsA (5 and 10 mg/kg) in mice significantly alleviated the T0901317-mediated increases in hepatocyte diameter and the percentage of regions in hepatic parenchyma occupied by lipid droplets. Furthermore, HsA significantly attenuated hepatic triglyceride accumulation by restoring the impaired expression of LXRα-dependent lipogenic genes caused by T0901317. Therefore, based on its inhibition of the LXRα-dependent signaling pathway, HsA has prophylactic potential for steatosis.

키워드

Fatty liver; Hemistepsin A (HsA); Liver X receptor; Sterol regulatory element-binding protein-1c; T0901317

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