Abstract
Nonalcoholic fatty liver disease (NAFLD) is increasingly common among patients with type 2 diabetes mellitus (T2DM). The two conditions can act synergistically to produce adverse outcomes. However, the therapeutic options for patients with NAFLD and T2DM are currently limited. Human umbilical cord-derived mesenchymal stem cells (UC-MSCs) have shown therapeutic potential for diabetes and hepatic disorders such as liver cirrhosis and fulminant hepatic failure. The present study is aimed at investigating the effect of human UC-MSCs on a mouse model of NAFLD and T2DM, characterized by obesity-induced hyperglycaemia, dyslipidaemia, hepatic steatosis, and liver dysfunction. Thirty-week-old male C57BL/6 db/db mice were infused with human UC-MSCs or phosphate-buffered saline (PBS) via the tail vein once a week for six weeks. Age-matched male C57BL/6 wild-type db/+ mice were used as controls. Body weight and random blood glucose were measured every week. One week after the sixth infusion, intraperitoneal glucose tolerance tests and insulin tolerance tests were performed and the blood and liver were harvested for biochemical and histopathological examinations. Quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR), immunofluorescence staining, and western blot were performed to monitor the expression of the lipid metabolism- and regulatory pathway-related genes. UC-MSC infusions significantly ameliorated hyperglycaemia, attenuated the elevation of hepatic transaminases, and decreased lipid contents, including triglyceride, total cholesterol, and low-density lipoprotein cholesterol. Moreover, histological lesions in the liver diminished markedly, as evidenced by reduced lipid accumulation and attenuated hepatic steatosis. Mechanistically, UC-MSCs were found to regulate lipid metabolism by increasing the expression of fatty acid oxidation-related genes and inhibiting the expression of lipogenesis-related genes, which were associated with the upregulation of the HNF4α-CES2 pathway. Our results demonstrate that human UC-MSCs can ameliorate NAFLD and reverse metabolic syndrome in db/db mice. Thus, UC-MSCs may serve as a novel therapeutic agent for T2DM patients with NAFLD.
Highlights
With the changes in diet and lifestyle, obesity has become an alarming health crisis of the 21st century
These results indicated that umbilical cord-derived mesenchymal stem cells (UC-Mesenchymal stem cells (MSCs)) infusions can regulate lipid metabolism by promoting fatty acid β-oxidation and suppressing lipogenesis, which accounted for the amelioration of nonalcoholic fatty liver disease (NAFLD)
The results showed that UC-MSC treatment alleviated hepatic functional injury, attenuated hepatic steatosis, and reduced hepatic lipid accumulation, as evidenced by markedly decreased serum levels of alanine transaminase (ALT) and AST, lowered AST to ALT (AST/ALT) ratio, Relative mRNA expression Relative mRNA expression
Summary
With the changes in diet and lifestyle, obesity has become an alarming health crisis of the 21st century. Global estimates indicate that about 500 million people have obesity and are at risk of significant obesity-related morbidity [1]. Type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD) are both obesity-associated metabolic diseases, and they often coexist. The prevalence of NAFLD among T2DM patients is nearly 70%, which is at least 2fold higher than that in the general population [2, 3]. In T2DM patients with NAFLD, extra lipid accumulation in the liver leads to hepatocyte dysfunction, which adversely affects the glycaemic control and increases the likelihood of developing diabetic complications. The presence of T2DM worsens the course of
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
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 call
