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Sennoside A Protects Mitochondrial Structure and Function to Improve High-Fat Diet-Induced Hepatic Steatosis by Targeting VDAC1

Sennoside A Protects Mitochondrial Structure and Function to Improve High-Fat Diet-Induced Hepatic Steatosis by Targeting VDAC1

Jiamei Le, Weiping Jia, Yongning Sun

Biochem Biophys Res Commun. 2018 Jun 2;500(2):484-489.

PMID: 29673597

Abstract:

Mitochondrial dysfunction is mainly associated with high-fat-diet (HFD)-induced hepatic steatosis. Sennoside A (SA), a commonly used clinical stimulant laxative, is reported to improve energy metabolism and insulin resistance. However, the effect and mechanism of SA on HFD-induced hepatic steatosis remain largely unknown. The aim of this study was to determine the effect and mechanism of SA on HFD-induced hepatic steatosis in mice. We examined the liver and body weight of mice to evaluate the physical changes in the liver. Hematoxylin and eosin (H&E) and oil red O staining were used to detect the lipid accumulation. The mitochondrial structure and function were tested by transmission electron microscopy and the Seahorse XF24 Analyzer. Furthermore, mitochondrial complexes I, II, and IV and voltage-dependent anion channel 1 (VDAC1) protein activity were detected to understand the mechanism of the protective effect on mitochondria. As a result, damage to the structure and function in the hepatic mitochondria of HFD-induced hepatic steatosis was observed in mice. The structural damage was in the form of loss of cristae, mitochondrial swelling, vacuolization and even rupturing of the outer mitochondrial membrane (OMM). Functional alterations were found by activation of complex I and deficiency in complexes II and IV. The VDAC1 activity and the total ATP in the liver tissue was increased under hepatic steatosis conditions. The above effects were reversed by SA. These data suggest that inhibition of VDAC1 may be an underlying mechanism of SA for protecting mitochondria in HFD-induced hepatic steatosis in mice. Thus, VDAC1 may be a promising target for treating fatty liver disease.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP81276-A	Sennoside A		81-27-6	Price

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