Abstract
BackgroundNon-alcoholic fatty liver disease (NAFLD) caused by liver lipid dysregulation is linked to obesity. Somatostatin (SST) and its analogs have been used to treat pediatric hypothalamic obesity. However, the application of such drugs for the treatment of NAFLD has not been evaluated.ObjectiveThis study aimed to investigate the expression levels of important regulators of hepatic lipid metabolism and the possible effect of the SST analog octreotide on these regulators.MethodsSD rats were assigned to a control group and a high-fat diet group. Obese rats from the high-fat diet group were further divided into the obese and octreotide-treated groups. The body weight, plasma SST, fasting plasma glucose (FPG), insulin, triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and free fatty acid (FFA) levels were measured. Hepatic steatosis was evaluated based on the liver TG content, HE staining and oil red O staining. The SREBP-1c, ACC1, FAS, MTP, apoB and ADRP expression levels in the liver were also determined by RT-PCR, qRT-PCR, western blot or ELISA.ResultsThe obese rats induced by high-fat diet expressed more SREBP-1c, FAS and ADRP but less MTP protein in the liver than those of control rats, whereas octreotide intervention reversed these changes and increased the level of apoB protein. Compared to the control group, obese rats showed increased liver ACC1, SREBP-1c and apoB mRNA levels, whereas octreotide-treated rats showed decreased mRNA levels of apoB and SREBP-1c. This was accompanied by increased body weight, liver TG contents, FPG, TG, TC, LDL-C, FFA, insulin and derived homeostatic model assessment (HOMA) values. Octreotide intervention significantly decreased these parameters. Compared to the control group, the obese group showed a decreasing trend on plasma SST levels, which were significantly increased by the octreotide intervention.ConclusionOctreotide can ameliorate hepatic steatosis in obese rats, possibly by decreasing hepatic lipogenesis and increasing TG export from hepatocytes.
Highlights
Non-alcoholic fatty liver disease (NAFLD) is closely related to diabetes and obesity [1, 2] and has become a primary disease endangering public health
The SREBP1c, ACC1, fatty acid synthase (FAS), Microsomal triglyceride transfer protein (MTP), apolipoprotein B (apoB) and adipose differentiation-related protein (ADRP) expression levels in the liver were determined by reverse transcription (RT)-polymerase chain reaction (PCR), Quantitative real-time PCR (qRT-PCR), western blot or Enzyme-linked immunosorbent assay (ELISA)
The obese rats induced by high-fat diet expressed more SREBP-1c, FAS and ADRP but less MTP protein in the liver than those of control rats, whereas octreotide intervention reversed these changes and increased the level of apoB protein
Summary
Non-alcoholic fatty liver disease (NAFLD) is closely related to diabetes and obesity [1, 2] and has become a primary disease endangering public health. NAFLD is manifested by the accumulation of lipids in the liver in the absence of excess alcohol consumption, caused by the imbalance between lipid input (fatty acid uptake and de novo lipogenesis) and output (VLDL export and fatty acid β-oxidation) [4]. Acetyl-CoA carboxylase (ACC1) and fatty acid synthase (FAS) are the regulatory enzymes for hepatic lipid synthesis. Insulin regulates the transcription and activation of liver sterol regulatory element binding protein-1c (SREBP-1c), which participates in liver fatty acid synthesis by stimulating the expression of ACC1 and FAS. Non-alcoholic fatty liver disease (NAFLD) caused by liver lipid dysregulation is linked to obesity. The application of such drugs for the treatment of NAFLD has not been evaluated
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
