Pentoxifylline ameliorates non-alcoholic fatty liver disease in hyperglycaemic and dyslipidaemic mice by upregulating fatty acid β-oxidation.
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.
Research Center for Industry of Human Ecology, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, Taiwan.
Jia-Hung
JH
Ye
Institute of Pharmacology, College of Medicine, National Yang-Ming University, Taipei, Taiwan.
Jung
J
Chao
Liver Research Center, Division of Hepatology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linko, Taiwan.
Ming-Ling
ML
Chang
Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, College of Pharmacy, China Medical University, Taichung, Taiwan.
Wen-Huang
WH
Peng
Department of Nursing, Chung Jen College of Nursing, Health Sciences and Management, Chia-Yi, Taiwan.
Hao-Yuan
HY
Cheng
Graduate Institute of Veterinary Pathology, National Chung Hsing University, Taichung, Taiwan.
Jiunn-Wang
JW
Liao
Research Center for Industry of Human Ecology, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, Taiwan.|Graduate Institute of Health-Industry Technology, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, Taiwan.|Department of Nutrition and Health Sciences, Chang Gung University of Science and Technology, Kweishan, Taoyuan, Taiwan.
Li-Heng
LH
Pao
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D004041:Dietary Fats / Q000009:adverse effects / Q000494:pharmacology; D050171:Dyslipidemias / Q000139:chemically induced / Q000178:diet therapy / Q000378:metabolism / Q000473:pathology; D005227:Fatty Acids / Q000378:metabolism*; D006943:Hyperglycemia / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D065626:Non-alcoholic Fatty Liver Disease / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D010084:Oxidation-Reduction / Q000187:drug effects; D010431:Pentoxifylline / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects*
D004041:Dietary Fats; D005227:Fatty Acids; D010431:Pentoxifylline