| BackgroundObesity is a chronic metabolic disease caused by the more caloric intake than consumption,the symptom of which are the abnormal increase of body fat and overweight.The lack of exercise in daily life and the excessive intake of high-calorie food lead to the rising obesity rate in recent years,which severely threatens human health.The browning of white adipose tissue refers to the appearance of brown fat-like changes in white fat,which promotes energy consumption and alleviates obesity.Myeloid-derived growth factor(MYDGF)is a kind of secreted protein mainly derived from bone marrow cells,which has been proved to promote cardiac repair and angiogenesis after myocardial infarction,improve metabolism in diabetic mice,relieve diabetic nephropathy and atherosclerosis.However,the effects of MYDGF on the browning of white adipose tissue remains unclear.AimsThis study aimed to explore the effects of MYDGF on browning of white adipose tissue and obesity,as well as its possible regulatory mechanism.MethodsIn vivo experiments,the effects of MYDGF deficiency on obesity were firstly investigated:myeloid cell specific MYDGF gene knockout mice(KO)and wild type mice(WT)were fed a high-fat-diet to construct obesity models,and the changes of body weight were recorded,Lee’s index was calculated,the heat production and serum lipid levels were measured.The visceral white adipose,subcutaneous white adipose tissue and interscapular brown adipose tissue of mice were dissected and weighed,and the proportions of adipose tissue were calculated.In subcutaneous adipose tissue,HE staining was used to observe the morphology of subcutaneous adipocytes,immunohistochemistry was used to investigate the expression of uncoupling protein 1(UCP1),and quantitative real-time polymerase chain reaction was used to detect the mRNA relative expression levels of browning-related genes.In addition,the effect of MYDGF replenishment on the browning of white adipose tissue in obese mice was investigated by injection of adeno-associated virus AAV-MYDGF in bone marrow cavity in situ,and the above indexes were detected.Besides,transmission electron microscopy was used to observe the mitochondria in subcutaneous adipose tissue,and immunofluorescence was used to detect the mitochondria and vessels of subcutaneous adipose tissue.In vitro experiments,mouse 3T3-L1 preadipocytes were cultured and induced to differentiate and mature,and the observation of lipid droplets were carried out by oil red O staining.Recombinant MYDGF(rMYDGF)was used for intervention.MTT was used to detect the effects of different concentrations of rMYDGF on cell activity at different times,while qRT-PCR and western blot were used to measure the changes of mRNA and protein relative expression levels of browning-related genes after rMYDGF intervention.ResultsThe results of in vivo experiments showed that the deficiency of MYDGF increased the body weight and Lee’s index of obese mice induced by high-fat-diet,aggravated dyslipidemia,increased the visceral adipose tissue weight and proportion,decreased thermogenesis,increased the size of subcutaneous adipocytes and decreased the expression level of some browning-related genes in subcutaneous adipose tissue.After MYDGF replenishment,obesity of mice fed a high-fat-diet was alleviated,the body weight and Lee’s index were decreased,lipid metabolism was improved,visceral adipose tissue weight and proportion were decreased,thermogenesis was increased,the size of subcutaneous adipocytes was decreased,while the expression of browningrelated genes,the number of mitochondria and vascular distribution were increased in subcutaneous adipose tissue.The results of in vitro experiments showed that rMYDGF intervention increased the expression level of browning-related genes of 3T3-L1 adipocytes.ConclusionMYDGF can promote the browning of white adipose tissue,thus alleviating obesity.The mechanism may be related to improving the microcirculation of adipose tissue and acting on adipocytes directly. |
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