SUMO-specific protease 3 is a key regulator for hepatic lipid metabolism in non-alcoholic fatty liver disease

Abstract

Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive lipid accumulation in hepatocytes. The role of SENP3 in lipid metabolism, particularly NAFLD, is unclear. Our results showed that hepatic SENP3 was up-regulated in NAFLD patients and an animal model in vivo and after loading hepatocytes with free fatty acids (FFA) in vitro. Intracellular lipid accumulation was determined in SENP3 silenced or overexpressed hepatocytes with/without FFA in vitro. Confirming a role for SENP3, gene silencing was associated in vitro with amelioration of lipid accumulation and overexpression with enhancement of lipid accumulation. SENP3 related genes in NAFLD were determined in vitro using RNA-Seq. Eleven unique genes closely associated with lipid metabolism were generated using bioinformatics. Three selected genes (apoe, a2m and tnfrsf11b) were verified in vitro, showing apoe, a2m and tnfrsf11b were regulated by SENP3 with FFA stimulation. Intrahepatic and circulating APOE, A2M and TNFRSF11B were elevated in NAFLD compared with controls. These data demonstrate the important role of SENP3 in lipid metabolism during the development of NAFLD via downstream genes, which may be useful information in the development of NAFLD. The precise role of SENP3 in NAFLD will be investigated using liver-specific conditional knockout mice in future studies.

Berberine ameliorates blockade of autophagic flux in the liver by regulating cholesterol metabolism and inhibiting COX2-prostaglandin synthesis

“…The corresponding cDNA libraries were constructed using the TruSeq Stranded Total RNA LT Sample Prep Kit (Illumina, Santiago, CA, USA) by Genergy Biological Technology Limited Co. (Shanghai, China) and sequenced with Illumina Hiseq3000. RNA-Seq reads were aligned to the reference data downloaded from UCSC (version hg19), and the RPKM method was utilized to normalize the reads that exclusively mapped to a gene, to quantify the transcript levels 50 , 51 .…”

Not So Slim Anymore—Evidence for the Role of SUMO in the Regulation of Lipid Metabolism

“…The SUMO protease SENP3 was upregulated in the liver of NAFLD patients and rats fed on a high-fat diet. Importantly, following free fatty acid treatment, lipid accumulation in human hepatocytes was markedly reduced by a SENP3-siRNA and increased by SENP3 overexpression [109]. This functional link between de-SUMOylation and the accumulation of lipids was further supported by the finding that SENP3 positively regulates the expression of several proteins that are involved in the transport of lipids to the cell, such as Apolipoprotein E [109].…”

“…Importantly, following free fatty acid treatment, lipid accumulation in human hepatocytes was markedly reduced by a SENP3-siRNA and increased by SENP3 overexpression [109]. This functional link between de-SUMOylation and the accumulation of lipids was further supported by the finding that SENP3 positively regulates the expression of several proteins that are involved in the transport of lipids to the cell, such as Apolipoprotein E [109]. Although the exact mechanistic basis of the function of SENP3 in NAFLD is yet to be characterized, this finding draws a causal link between SUMOylation, dysregulated lipid metabolism, and NAFLD.…”

“…A recent study has highlighted a possible connection between SUMO and Nonalcoholic Fatty Liver Disease (NAFLD), which is characterized by an excessive accumulation of lipids in hepatocytes [109]. The SUMO protease SENP3 was upregulated in the liver of NAFLD patients and rats fed on a high-fat diet.…”

Correlation between hepatic human males absent on the first (hMOF) and viral persistence in chronic hepatitis B patients

“…Every test was coupled with a negative control in which the antibody was substituted by the primary rabbit negative control. Immunohistochemical assay and computer-assisted genuine color image analysis system (ImagePro-plus 7.0) was used to quantify objectively the integrated optional density of hepatic hMOF [ 18 , 19 ].…”