Abstract

Obesity is a global public health concern associated with increased risk of several comorbidities. Due to the limited effectiveness of current therapies, new treatment strategies are needed. Our aim was to examine the effect of adipose-derived mesenchymal stem cells (AD-MSCs) on obesity and its associated diseases in a diet-induced obese (DIO) animal model. C57BL6 mice were fed with either high fat diet (HFD) or CHOW diet for 15 weeks. Obese and lean mice were then subjected to two doses of AD-MSCs intraperitoneally. Mice body weight and composition; food intake; blood glucose levels; glycated hemoglobin (HbA1c), intraperitoneal glucose tolerance test and atherogenic index of plasma (AIP) were measured. Pro-inflammatory cytokines, tumor necrosis factor-α and interleukin-6, were also determined. AD-MSCs treatment reduced blood glucose levels, HbA1c and AIP as well as improved glucose tolerance in DIO mice. In addition, MSCs caused significant attenuation in the levels of inflammatory mediators in HFD-fed mice. Taken together, AD-MSCs were effective in treating obesity-associated diabetes in an animal model as well as protective against cardiovascular diseases as shown by AIP, which might be partly due to the attenuation of inflammatory mediators. Thus, AD-MSCs may offer a promising therapeutic potential in counteracting obesity-related diseases in patients.

Highlights

  • Of collection, rapid expansion and high proliferation ­capacity[11]

  • Mice were fed for 15 weeks with either a high-fat diet (HFD) to generate diet-induced obese (DIO) mice or a standard CHOW diet to produce lean mice (Fig. 1a)

  • Obesity is a serious public health concern that increases the chances of developing numerous diseases such as diabetes, cardiovascular diseases and other ­comorbidities[4]

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Summary

Introduction

Of collection, rapid expansion and high proliferation ­capacity[11]. studies have confirmed that they can maintain the basic phenotype of MSCs over long-term culture up to Passage 1­ 011. Stem cell therapy in obesity and its related diseases has been suggested by several animal studies but results seem to be unclear, making it far and difficult to move into clinical s­ ettings[12,13,14]. Well-designed studies are needed to determine efficacy in the animal model before proceeding to humans. The purpose of this study was to investigate the effect of AD-MSCs on body weight, body composition, glycaemic control and dyslipidaemia in an in vivo animal model. An experimental model of obesity was established in mice under chronic high-fat diet (HFD) feeding for 15 weeks. The therapeutic potential of intraperitoneal AD-MSC infusion to treat dietary-induced obesity and its associated disorders such as diabetes and CVD in a mouse model of HFD–induced obesity was elucidated in this study. The mechanism by which AD-MSCs produce their therapeutic effects was explored

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