Dataset Information

Effect of Octreotide on Hepatic Steatosis in Diet-Induced Obesity in Rats.

ABSTRACT: BACKGROUND:Non-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. OBJECTIVE:This 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. METHODS:SD 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. RESULTS: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. 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. CONCLUSION:Octreotide can ameliorate hepatic steatosis in obese rats, possibly by decreasing hepatic lipogenesis and increasing TG export from hepatocytes.

SUBMITTER: Li M

PROVIDER: S-EPMC4803296 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Effect of Octreotide on Hepatic Steatosis in Diet-Induced Obesity in Rats.

Li Mao M Ye Ting T Wang Xiao-Xia XX Li Xian X Qiang Ou O Yu Tao T Tang Cheng-Wei CW Liu Rui R

PloS one 20160322 3

<h4>Background</h4>Non-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.<h4>Objective</h4>This 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.<h4> ...[more]

PMID: 27002331

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Project description:Reduced hepatic glycogenesis is one of the most important causes of metabolic abnormalities in non‑alcoholic fatty liver disease. Octreotide, a somatostatin analogue, has been demonstrated to promote weight loss and improve metabolic disorders in mice with high fat diet (HFD)‑induced obesity. However, whether octreotide affects hepatic glycogenesis is unknown. The aim of the present study was to verify the effects of octreotide on hepatic glycogenesis in rats with HFD‑induced obesity. Male Sprague‑Dawley rats were fed a standard diet or a HFD for 24 weeks. Obese rats from the HFD group were further divided into a HFD‑control group and an octreotide‑administered group. Rats in the latter group were injected with octreotide for 8 days. Glucose and insulin tolerance tests were performed, and the area under the curve (AUC) was calculated. Following sacrifice, their body weights and lengths, fasting plasma glucose (FPG), fasting insulin (FINS), serum triglyceride (TG), total cholesterol (TC), free fatty acid (FFA), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured. In addition, Lee's index and the homeostatic model assessment index were calculated. Hepatic TG, FFA levels and glycogen content were first determined. Hepatic steatosis in the obese rats was assessed based on hematoxylin and eosin and Oil Red O staining. Human hepatoblastoma HepG2 cells were divided into a control group, a palmitate (PA)‑treated group and a PA + octreotide‑treated group. Establishment of the in vitro fatty liver model using HepG2 cells was confirmed by Oil Red O staining. The expression of phosphorylated Akt and glycogen synthase kinase 3β (GSK3β) was detected by western blotting, and glycogen synthase (GS) mRNA levels were detected by reverse transcription‑quantitative polymerase chain reaction. Compared with the control group, the body weight, Lee's index, AUC of the intraperitoneal glucose tolerance test and intraperitoneal insulin tolerance test, levels of FPG, FINS, TG, TC, FFA, ALT and AST, and HOMA index values were significantly increased in the obese rats. The body weight, levels of FPG and FINS, and the HOMA index were significantly reduced following octreotide treatment, whereas the decrease in Lee's index, the blood levels of ALT, AST, TC, TG and FFA, and the AUC did not reach statistical significance. Hepatic TG and FFA levels were significantly increased and hepatic glycogen content was significantly decreased in rats with HFD‑induced obesity when compared with those in the control group. Octreotide intervention restored these alterations. The expression levels of phosphorylated Akt and GSK3β protein expression, as well as GS mRNA levels in the HFD group were lower when compared with those in the control group, whereas octreotide treatment reversed these reductions. The in vitro experiments demonstrated that the reduced levels of phosphorylated Akt and GSK3β protein, and GS mRNA in the PA‑treated group were significantly reversed by octreotide treatment. In conclusion, the results indicate that octreotide improved hepatic glycogenesis and decreased FPG concentration in rats with HFD‑induced obesity. These mechanisms may be associated with increased GS activity via the promotion of GSK3β phosphorylation. Therefore, octreotide may be regarded as a novel therapeutic strategy for HFD‑induced obesity and obesity‑associated metabolic disorders.

Dataset Information

Effect of Octreotide on Hepatic Steatosis in Diet-Induced Obesity in Rats.

Publications

Effect of Octreotide on Hepatic Steatosis in Diet-Induced Obesity in Rats.

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