Mechanisms Research On Effects Of High Fat-Diet On Sacropenia

Objective.With the development of social economy,dietary structure was westernized gradually,such as High fat diet(HFD),which promoted the morbidity of metabolic syndrome and cardiovascular disease.High fat diet is considered to be one of the important risk factors of threat to human health.The Western lifestyle inducing chronic inflammation reaction and oxidative stresses,as a accelerator of aging,which promoted the senile disease like sarcopenia.Skeletal muscle mass and function decline with aging,a process known as sarcopenia,which restrains posture maintenance,frailty,disability and mobility and quality of life in the elderly,as a new old syndrome making major attention.With aging,the muscle protein balance tend to muscle degradation,as well as a loss of regenerative capacity.The decline of the muscle regenerative capacity with age is very significant to sacropenia.Muscle stem cells in older less muscle disease as a"cornerstone" role,repiaring skeletal muscle regeneration,improving the function of stem cells,can delay less muscle disease.Now with the progress of the study,strengthen the function of skeletal muscle stem cells proliferation and differentiation,can become less slow muscle disease.Methods.In vivo study,The C57BL/6J mice were randomly divided into the normal diet group and high fat diet group,in order to analyze the effects of western life style(a high-fat diet)on muscle fiber size and strength in mice.The Dual-energy X-ray was used to detect the body composition,acquire the mass of muscle and adipose tissue.Mice grip strength were measureed by Holding power.The Gastrocnemius muscle and Tibialis anterio were dissected,using hematoxylin-eosin(H&E)staining to observe the cross-sectional area of muscle fiber size.The expression of the genes was determined by real time PCR,such as tumor suppressor genes(P53,and P16),muscle protein ubiquitin protein degradation ligase E3s(Atrogin-1,MuRP-1),and inflammatory cytokines(IL-6,TNF ?)and 11 ?Hydroxysteroid Dehydrogenase(11?-HSD1).In vitro research,Palmitic acid were added to skeletal muscle stem cells,analyzing the effect of free fatty acids on differentiation and function of skeletal muscle stem cells.PA and PA+BVT were added to skeletal muscle stem cells.The morphological changes of the cultured cells were observed.The MyHC of the culture cells was determined using immunocytochemistry and the expression of the gene was determined by real time PCR.Oxygen consumption rates(OCR)was measured by XFe24 extra cellular flux analyzer.The levels of mitochondrial fusion and fission marks such as Mfn1,Opal,Drpl,Fisl were measured.Results.In Animal experiments,we found that mice which were fed a high-fat diet were easy to gain more adipose tissue obviously,smaller muscle mass and skeletal muscle fiber size,adipose tissue were observed between muscle,and the grip strength of mice were relatively reduced.The expression of the gene P16 was increased after feeding a high fat diet(P<0.05).We tasted atrophy genes Atrogin-1,MuRF-land cytokins,finding gene expression of Atrogin-1,MuRF-1,IL-6,TNFa were increased.11?-HSD1 were increased after a high fat Dietary.When muscle stem cells were treated with PA,fluorescent expression of MyHC were decreased and the fusion rate of myotube also reduced.The OCR in the presence of PA was decreased(P<0.05).The fusion marks was no significant change,but mitochondrial fusion index(Mfnl-to-Drp1ratio)was significantly increased.These changes can be reversed by BVT.2733.Conclusions.In brief,high-fat diets is a accelerator of aging,changing the body composition,characterized by a decline in mass and to a decrease in the number,size,and quality of contractile myofibers.11?-HSD1 inhibited the differentiation of skeletal muscle stem cells and oxygen consumption rate of mitochondria.The BVT.2733 can improve the function of muscle stem cells,becoming a new effective treatment to delay the development of muscle wasting.