Abstract
BackgroundHepatic steatosis is a big hurdle to treat type 2 diabetes (T2D). Fasting-mimicking diet (FMD) has been shown to be an effective intervention in dyslipidemia of T2D. However, fasting may impair the normal glucose metabolism. Human umbilical cord-derived mesenchymal stem cell (UC-MSC) transplantation has been discovered to regulate immune reactions and reduce hyperglycemia in diabetes. However, the effect of UC-MSCs on improving the lipid metabolism disorder is not quite satisfactory. We have investigated the efficacy comparison and interaction between FMD and UC-MSC infusion, aiming to establish effective T2D therapies and explore its mechanism.MethodsC57/BL6 mice were fed with high-fat diet (HFD) to induce a diet-induced obese (DIO) mouse model. Leptin receptor-deficient (db/db) mice were used for follow-up experiments. DIO or db/db mice were divided into 4 groups: phosphate buffer saline (PBS), UC-MSCs, FMD, and UC-MSCs + FMD. At the end of the study period, mice were fasted and sacrificed, with the measurement of physiological and biochemical indexes. In addition, the fresh liver, skin, and white adipose tissue were analyzed by histology.ResultsFMD restored the lipid metabolism in DIO mice, whereas its capacity to rescue hyperglycemia was uncertain. Infusion of UC-MSCs was effective in T2D glycemic control but the impact on dyslipidemia was insufficient. Furthermore, both the glucose and the lipid alterations of DIO and db/db mice recovered after UC-MSCs combined with FMD. It was proved that UC-MSCs promoted FMD effects on ameliorating hyperglycemia and restoring the lipid metabolism in T2D mice, while FMD had little promotion effect on UC-MSCs. Mechanistically, we discovered that UC-MSC infusion significantly modulated systematic inflammatory microenvironment, which contributed to concerted actions with FMD.ConclusionsWe established a strategy that combined UC-MSC infusion and FMD and was effective in treating T2D, which provided potential approaches for developing novel clinical T2D therapies.
Highlights
It is estimated that 415 million people worldwide are currently living with diabetes [1], resulting in plenty of patients with complications in the liver, kidney, the cardiovascular system, and so on
Infusion of umbilical cord-derived mesenchymal stem cell (UC-Mesenchymal stem cells (MSCs)) was effective in type 2 diabetes (T2D) glycemic control but the impact on dyslipidemia was insufficient
It was proved that UC-MSCs promoted Fasting-mimicking diet (FMD) effects on ameliorating hyperglycemia and restoring the lipid metabolism in T2D mice, while FMD had little promotion effect on UC-MSCs
Summary
It is estimated that 415 million people worldwide are currently living with diabetes [1], resulting in plenty of patients with complications in the liver, kidney, the cardiovascular system, and so on. High-fat diet (HFD) results in the development of obesity which is a major risk factor for type 2 diabetes (T2D) [2, 3]. Noteworthy is that almost all patients with T2D display lipid accumulation in the liver causing hepatic steatosis, which represents a big hurdle to cure T2D [4, 5]. Fasting-mimicking diet (FMD), a kind of caloric restriction which represents a dietary mode low in calories, sugars, and proteins but high in unsaturated fats, can dramatically reduce triglycerides (TG) and total and low-density lipoprotein cholesterol, resulting in a loss of total body fat and a reduction of liver fat accumulation [6, 7]. Hepatic steatosis is a big hurdle to treat type 2 diabetes (T2D). We have investigated the efficacy comparison and interaction between FMD and UC-MSC infusion, aiming to establish effective T2D therapies and explore its mechanism
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
