Effects of Sitagliptin on Nonalcoholic Fatty Liver Disease in Diet-Induced Obese Rats

Akaslan, S.; Değertekin, Ceyla Konca; Yılmaz, Güldal; Çakır, Nuri; Arslan, Metin; Törüner, Füsun Baloş

doi:10.1089/met.2012.0128

Cited by 32 publications

(24 citation statements)

References 37 publications

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“…DPP-4 is a peptidase which acts as inhibiting peptides, such as GLP-1, inducing glucose intolerance and hepatic steatosis. In animal models, DPP-4 inhibitors (i.e., sitagliptin, vildagliptin and saxagliptin) improve hepatic steatosis by ameliorating insulin sensitivity and hepatic triglyceride content [81]. Similar results have been reported in studies conducted in rats with GLP-1 analogs resistant to DPP-4 activity (i.e., exenatide, liraglutide) [82].…”

Section: Promising Future Agentssupporting

confidence: 69%

Current pharmacotherapy for treating pediatric nonalcoholic fatty liver disease

Corte

Liccardo

Ferrari

et al. 2014

Expert Opinion on Pharmacotherapy

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Section: Promising Future Agentssupporting

confidence: 69%

Current pharmacotherapy for treating pediatric nonalcoholic fatty liver disease

Corte

Liccardo

Ferrari

et al. 2014

Expert Opinion on Pharmacotherapy

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“…Studies have suggested that sitagliptin reduces hepatic lipid accumulation [26, 27]. However, the specific mechanism has not been fully elucidated.…”

Section: Resultsmentioning

confidence: 99%

Reduced miR-200b and miR-200c expression contributes to abnormal hepatic lipid accumulation by stimulating JUN expression and activating the transcription ofsrebp1

et al. 2016

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Previous studies indicated that miR-200s participated in IL-6-induced hepatic insulin resistance. However, the role of miR-200s in hepatic lipid accumulation has not been elucidated. Here we found that miR-200b and miR-200c were reduced in the steatotic livers of mice fed a high-fat diet (HFD) and patients with nonalcoholic fatty liver disease. This down-regulation was accompanied by an increase in the expression of lipogenic proteins such as sterol regulatory element-binding protein 1 (SREBP1) and fatty acid synthase (FAS). The suppression of miR-200b and miR-200c in Hep1-6 and NCTC1469 hepatocytes enhanced intracellular triglyceride levels, which were associated with increased SREBP-1 and FAS protein levels. In contrast, the over-expression of miR-200b and miR-200c suppressed lipid accumulation and reduced the expression of SREBP1 and FAS in Hep1-6 and NCTC1469 cells transfected with miR-200b or miR-200c mimics. Importantly, the up-regulation of miR-200b and miR-200c could reverse oleic acid/palmitic acid-induced lipid accumulation in hepatocytes. A luciferase reporter assay identified that miR-200b and miR-200c could directly bind the 3′UTR of jun. JUN activated the transcription of srebp1 to increase lipid accumulation. The data also demonstrated that increased miR-200b and miR-200c expression might be associated with sitagliptin-reduced hepatic lipid accumulation in mice fed a HFD. These findings suggest, for the first time, that reduced miR-200b and miR-200c expression contributes to abnormal hepatic lipid accumulation by stimulating JUN expression and activating the transcription of srebp1.

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“…In rat models, DPP-4 inhibitors improve hepatic steatosis by increasing insulin sensitivity and decreasing hepatic triglyceride levels [66,67] . To date, there is no published controlled trial with these agents in humans.…”

Section: Dipeptidyl Peptidase 4 Inhibitorsmentioning

confidence: 99%

Insulin sensitizers for the treatment of non-alcoholic fatty liver disease

Öztürk

Kadayıfçı

2014

WJH

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Non-alcoholic fatty liver disease (NAFLD) is the leading cause of liver disease in the Western world and is closely associated with metabolic syndrome, which includes hypertension, central obesity, dyslipidemia and insulin resistance. NAFLD includes a wide spectrum of liver alterations, ranging from simple hepatic steatosis to variable degrees of fibrosis, cirrhosis and even hepatocellular carcinoma. Although the etiology and progression of the disorder remain poorly understood, insulin resistance is considered to play a pivotal role in the pathogenesis. Insulin sensitizers such as biguanides, thiazolidinediones (TZDs), glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase 4 inhibitors have been studied as therapeutic approaches for NAFLD in recent years. Metformin improves insulin sensitivity and serum alanine transaminase and aspartate transaminase (ALT/AST) levels in the majority of subjects; however, it has no significant effect on liver histology. TZDs improve insulin sensitivity, serum ALT/AST levels and histology in some cases, but there are some concerns about the safety of long-term therapy. Selection of appropriate patients for avoiding side effects and the treatment of underlying disease are the main points. These drugs are the best choice for the treatment of NAFLD in patients with type 2 DM who are also candidates for treatment with an insulin sensitizer. The present review provides an overview of insulin sensitizers in the treatment of NAFLD.

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Effects of Sitagliptin on Nonalcoholic Fatty Liver Disease in Diet-Induced Obese Rats

Abstract: Sitagliptin may improve hepatic steatosis by increasing insulin sensitivity and improving lipid profiles in rats.

Cited by 32 publications

References 37 publications

Current pharmacotherapy for treating pediatric nonalcoholic fatty liver disease

Current pharmacotherapy for treating pediatric nonalcoholic fatty liver disease

Reduced miR-200b and miR-200c expression contributes to abnormal hepatic lipid accumulation by stimulating JUN expression and activating the transcription ofsrebp1

Insulin sensitizers for the treatment of non-alcoholic fatty liver disease

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