Study On The Effects Of Trans-palmitoleic Acid On Obese Mice

With social and economic development,more and more people have become overweight or obese.Obesity has become one of the most common health problems in developed and developing countries in the 21st century.It has affected the life and work of 15%of the world’s population.Obesity often induces many metabolic disorders,especially such as type 2 diabetes.Therefore,the prevention and treatment of obesity is particularly urgent and important.Previous studies had shown that long-term intake of foods rich in saturated fatty acids and trans-fatty acids can lead to obesity,especially abdominal fat accumulation.However,recent clinical studies had shown that trans-palmitoleic acid can significantly improve insulin sensitivity,reduce the incidence of obesity and diabetes,and decrease atherosclerosis risk.However,due to clinical observational studies only provide the existence of correlation,it cannot rule out the inverse causality and accompanying phenomena,and also cannot deeply explore the mechanism.Therefore,animal experiments were used to systematically investigate the therapeutic and preventive effects of trans-palmitoleic acid on healthy mice and obese mice,and explored the underlying mechanism of effects.Previous studies have shown that long-term intake of foods rich in saturated fats and trans-fatty acids can lead to obesity,especially abdominal fat accumulation.However,the latest clinical observational studies have shown that the content of trans-palmitoleic acid is higher in obesity.However,only based on this correlation,it cannot be judged whether the correlation between trans-palmitoleic acid and obesity is a causal relationship,or only satellite phenomenon.And it cannot be judged whether trans-palmitoleic acid has a direct effect on obesity or not,and whether its effect is favorable or harmful.And the mechanism cannot be explored.On the other hand,another study found that trans-palmitoleic acid can reduce the incidence and risk of type 2 diabetes and atherosclerosis.Therefore,animal experiments were conducted to systematically investigate whether trans-palmitoleic acid has therapeutic or preventive effects on obese mice,and to explore the underlying mechanism of effects.C57BL/6J male mice were used and animal experiments were divided into 4 groups:injection-normal mice,injection-therapy obesity,injection-prevention obesity,oral-prevention obesity.In the above four experimental groups,the body weight,food intake,fasting blood glucose level,postprandial blood glucose level,glucose intolerance,insulin sensitivity,RER（respiratory exchange rate）,heat production,and activity of mice were observed.QPCR（Quantitative polymerase chain reaction）and WB（Western Blot）were respectively used to detect the expression of lipid-metabolism-related genes and inflammation-related proteins of mice.The main results are showed as follows:（1）In normal mice experiment,it was found that injection of free trans-palmitoleic acid significantly reduced transient blood glucose level of normal mice in a short period of time,but no significant adverse effect on body weight,fasting blood glucose,postprandial blood glucose,glucose tolerance and insulin sensitivity in normal mice.It indicated that trans-palmitoleic acid plays a role in the homeostasis of glucose metabolism.（2）In the treatment of obese mice,the injection of free trans-palmitoleic acid significantly reduced the serum triglyceride levels induced by high-fat diet in obese mice（p<0.05）,whereas it had no significant effect on body weight,appetite,glucose metabolism,liver function,serum total cholesterol（CHOL）level,high-density lipoprotein（HDL）level and low-density lipoprotein（LDL）level.It showed that the injection of palmoleic acid had no significant therapeutic effect on obese mice.（3）In the experiment of injection-preventing obesity,injection of free trans-palmitoleic acid slightly inhibited weight gain in obese mice,but this protective effect was not related to food intake.In addition,trans-palmitoleic acid increased O₂ consumption（p<0.05）,CO₂ release（p<0.05）,RER（p<0.01）,thermogenesis and activities,so that it enhance the output of energy.At the same time,it inhibited the growth of epididymal fat,subcutaneous fat and brown fat in obese mice.These results showed that trans-palmitoleic acid inhibits the weight gain of obese mice mainly by enhancing energy metabolism and inhibiting adipose tissue growth.It indicated that trans-palmitoleic acid regulates lipid metabolism.In addition,injection of trans-palmitoleic acid significantly reduced fasting blood glucose level in mice（p<0.05）and improved impaired glucose tolerance induced by high fat diet（p<0.01）,indicating that trans-palmitoleic acid participates in the regulation of glucose homeostasis.（4）In the experiment of oral-preventing obesity,orally taking with trans-palmitoleic acid significantly improved glucose intolerance（p<0.01）,inhibited appetite（p<0.0001）,increased O₂ consumption（p<0.0001）,CO₂ release（p<0.0001）,RER（p<0.0001）,and heat production（p<0.0001）,without affecting body weight,fasting blood glucose level,postprandial glucose level.However,it significantly decreased animal activity（p<0.0001）,finally leading to an energy balance status.In addition,trans-palmitoleic acid also reduced subcutaneous fat accumulation of mice by inhibiting the expression of lipogenesis genes（FASN,SREBP-1,PPAR-γ,PPAR-α）and fatty acid elongase-related genes（ACC-1,ELOVL6）（p<0.05）.While it had no significant effect on expression of genes involved in lipolysis（ATGL,HSL）,β-oxidation（ACOX-1,ACADM,ACADVL）and signaling involved in inflammation（p-Akt,p-Erk1/2,p-P38）.In conclusion,this study demonstrated that no significant side effects were observed in normal male mice injected with trans-palmitoleic acid and no significant therapeutic effect was observed in high fat-induced obese mice,while low-dose feeding and injection of trans-palmitoleic acid were both beneficial to obese mice.Among them,administration by tail vein is more effective than oral administration in the prevention and protection of blood glucose in obese and type 2 diabetic mice.It provides a certain theoretical basis and reference for the future development of prevention and treatment of obesity and diabetes-related nutraceutical foods and special dietary formulations.