The Effects Of Mechanical Loading On The Therapy Of Obesity And Non-alcoholic Fatty Liver

BackgroundObesity is a chronic disease,which is also a multifactorial energy and metabolic disorder,accompanied by excessive fat deposition.Lipids are important substances of energy storage and energy supply and also important structural components of biofilms.Abnormal fat metabolism can trigger a series of diseases,including atherosclerosis,hyperlipidemia,diabetes,fatty liver.The liver is the main metabolic organ,when dyslipidemia occurs,the most common disease is fatty liver.According to the World Health Organization,obesity is a leading,preventable cause of death worldwide,with ~ 2 billion overweight adults and ~ 600 million adults suffering from obesity.Postmenopausal women are more susceptible than premenopausal women,especially in the intra-abdominal depot,and they are sensitive to obesity-related metabolic disorder.Estrogen is a crucial hormone in resistance to obesity and progression of nonalcoholic fatty liver disease in women.Animal experiments have also shown that ovariectomized animals have high body weight and adipose tissue mass.Physical activities are recognized as an adjuvant therapy to reduce body weight,improve the fitness of the heart,lung,and overall quality of life.It is important to note that the elderly or physically handicapped individuals may have difficulty in fully receiving benefits from physical activities,and excessive activities may lead to a risk of muscle damage and bone fracture.Knee loading is a new type of joint loading rehabilitation physiotherapy,which is a treatment method that applies a certain frequency and size of loading force to the synovial joint laterally to achieve a non-invasive therapeutic effect.Our previous results showed that knee loading promoted the development of osteoblasts and inhibit osteoclastogenesis,such as osteoarthritis and osteoporosis.Osteoblasts and adipocytes are co-derived from mesenchymal stem cells.Although mechanical loading can effectively treat orthopedic diseases,the therapeutic effect on lipid metabolism-related diseases is also unknown.AimIn order to further investigate the therapeutic effect of knee loading on obesity and its related mechanisms,ovariectomy and high-fat diet induced two animal models of obesity were used in this study.To explore the following questions: whether knee loading can replace the active exercise to treat obesity and obesity-related fatty liver.In addition,based on the observation of the above therapeutic effects,we further investigated whether the mechanism of mechanical loading is via liver endoplasmic reticulum stress and autophagy.MathodsFifty 6-week old female C57 BL / 6 mice were randomly divided into five groups: control(SCD,n = 10),high fat diet(HF,n = 10),HF with loading(HF+L,n = 10),HF with ovariectomy(HF+OVX,n = 10),and HF+OVX with loading(HF+OVX+L,n = 10).In addition to SCD,mice underwent sham or bilateral ovariectomy and maintained a high-fat diet.After 6 weeks of modeling,mice in HF+L group and HF+OVX+L group were treated with knee loading for 6 weeks and the other three groups were treated with artificial knee loading.The treatment was bilateral knee mechanical loading,the loading frequency was 10 Hz,the loading force was 2N,the loading was 3min per day on each side,and the treatment was 5 days a week for 6 weeks.After six weeks of knee loading intervention,the orbit blood of mice was collected for lipids analysis,liver,inguinal fat pad,perirenal fat pad and uterine fat pad were weighed and recorded.Adipose tissue and liver were collected for histological analysis and western blot analysis for endoplasmic reticulum stress and autophagy-related protein expression.ResultsKnee loading significantly decreased a gain in body weight,liver weight,and visceral adipose tissue.The whole body fat content analysis showed that knee loading effectively reduced the total body fat content of the obese mice.It also reduced lipid levels in the serum.The results of pathologic histology showed that knee loading reduced lipid deposition,suggested that it reduced the severity of hepatic steatosis by decreasing liver lipid droplet deposition.In addition,the western blot of liver tissue indicated that knee loading reduced the levels of proteins associated with endoplasmic reticulum stress,and also regulated autophagy related proteins.