Abstract
Hyperlipidemia is a chronic disorder that plays an important role in the development of cardiovascular diseases, type II diabetes, atherosclerosis, hypertension, and non-alcoholic fatty liver disease. Hyperlipidemias have created a worldwide health crisis and impose a substantial burden not only on personal health but also on societies and economies. Transcription factors in the sterol regulatory element binding protein (SREBP) family are key regulators of the lipogenic genes in the liver. SREBPs regulate lipid homeostasis by controlling the expression of a range of enzymes required for the synthesis of endogenous cholesterol, fatty acids, triacylglycerol, and phospholipids. Thereby, SREBPs have been considered as targets for the treatment of metabolic diseases. The aim of this study was to investigate the beneficial functions and the possible underlying molecular mechanisms of SREBP decoy ODN, which is a novel inhibitor of SREBPs, in high-fat diet (HFD)-fed hyperlipidemic mice. Our studies using HFD-induced hyperlipidemia animal model revealed that SREBB decoy ODN inhibited the increased expression of fatty acid synthetic pathway, such as SREBP-1c, FAS, SCD-1, ACC1, and HMGCR. In addition, SREBP decoy ODN decreased pro-inflammatory cytokines, including TNF-α, IL-1β, IL-8, and IL-6 expression. These results suggest that SREBP decoy ODN exerts its anti-hyperlipidemia effects in HFD-induced hyperlipidemia mice by regulating their lipid metabolism and inhibiting lipogenesis through inactivation of the SREPB pathway.
Highlights
Non-alcoholic fatty liver disease (NAFLD) is a medical condition characterized by the deposition of fat in the liver [1]
The mature sterol regulatory element binding protein (SREBP)-1 is translocated into the nucleus where it can bind to the sterol regulated element-1 (SRE-1)
We investigated the inhibition of SREBP activity by the SREBP decoy ODN in high-fat diet (HFD)-fed hyperlipidemic mice
Summary
Non-alcoholic fatty liver disease (NAFLD) is a medical condition characterized by the deposition of fat in the liver [1]. NAFLD is used to describe a range of conditions from a simple deposition of triglycerides in hepatocytes to a condition involving hepatitis, fibrosis, and cirrhosis [2]. This pathogenesis of NAFLD is complex and strongly associated to be a hepatic expression of the metabolic syndrome, arising together with type II diabetes, insulin resistance, and obesity [3]. Hyperlipidemia is a chronic disorder that plays a major role in the progression of cardiovascular diseases, type II diabetes, hypertension, atherosclerosis, and NAFLD [4]. Beneficial and secure pharmacological interventions for hyperlipidemia are urgently needed
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