Pentoxifylline ameliorates non-alcoholic fatty liver disease in hyperglycaemic and dyslipidaemic mice by upregulating fatty acid β-oxidation.

Abstract

Nonalcoholic fatty liver disease (NAFLD), which includes simple steatosis, steatohepatitis, fibrosis, and cirrhosis, is characterised by abnormal fat accumulation in the liver in the absence of excessive alcohol intake. In patients with type 2 diabetes (T2D), concurrent NAFLD might increase the risk of chronic kidney disease and the mortality rate. Although several studies have examined the effectiveness of pentoxifylline (PTX) in NAFLD treatment, no results are available to verify the effectiveness of PTX in treating T2D associated with NAFLD. In this study, we developed a combined high-fat diet-induced obesity and low-dose streptozocin-induced hyperglycaemia mouse model to mimic the concurrent NAFLD and T2D pathological condition. By combining physiological assessments, pathological examinations, metabolomics studies on blood, urine, and liver, and measurements of gene and protein expression, we elucidated the effectiveness and the underlying mechanism of action of PTX in the hyperglycaemic and dyslipidaemic mice. Our results revealed that PTX ameliorated NAFLD in the hyperglycaemic and dyslipidaemic mice by upregulating fatty acid β-oxidation. Furthermore, the glycolysis pathway and branched-chain amino acid-related pathways in these mice were restored by PTX.

• Authors: Jia-Hung Ye, Jung Chao, Ming-Ling Chang, Wen-Huang Peng, Hao-Yuan Cheng, Jiunn-Wang Liao, Li-Heng Pao
• Journal: Scientific reports (Sci Rep) Vol. 6 Pg. 33102 (09 09 2016) ISSN: 2045-2322 [Electronic] England
• PMID: 27612024 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Dietary Fats
• Fatty Acids
• Pentoxifylline

Topics

• Animals
• Diabetes Mellitus, Experimental (drug therapy, metabolism, pathology)
• Diabetes Mellitus, Type 2 (chemically induced, drug therapy, metabolism, pathology)
• Dietary Fats (adverse effects, pharmacology)
• Dyslipidemias (chemically induced, diet therapy, metabolism, pathology)
• Fatty Acids (metabolism)
• Hyperglycemia (chemically induced, drug therapy, metabolism, pathology)
• Male
• Mice
• Non-alcoholic Fatty Liver Disease (chemically induced, drug therapy, metabolism, pathology)
• Oxidation-Reduction (drug effects)
• Pentoxifylline (pharmacology)
• Up-Regulation (drug effects)