Molecular Mechanism And Energetics Significance Of Negative Correlation Between Leptin And Body Fat In Tupaia Belangeri

Leptin is a signal protein coded by obesity gene,secreted by the white adipose tissue,with a molecular weight of 16 k Da,and the main function of leptin is to regulate animal food intake and energy metabolism of animals.The positive correlation between leptin concentration and body fat is a base to exercise its energy regulation function.Because its concentration is positively correlated with body fat,it can represent the energy reserve of the body and faithfully transmit information to the downstream to regulate energy homeostasis.High concentration of leptin can act on the hypothalamus to inhibit animal appetite and thus reduce energy intake,while low concentration of leptin will stimulate animal eating behavior.Researches also revealed that leptin can regulate energy expenditure in addition to regulating energy intake,which is achieved by promoting heat production and energy consumption of adipose tissue.These studies all show that leptin concentration plays a key role in the exercise of energy homeostasis regulation,and that leptin concentration is the key.Previous studies have shown that there is a positive correlation between serum leptin concentration and body fat.However,in a new experimental animal,Tupaia belangeri,research found that its leptin concentration was negatively correlated with body fat.This abnormal phenomenon in the kingdom of life arouses our interest,and may also expand the knowledge of the leptin and energy metabolism.Therefore,the molecular mechanism of this negative correlation and the energy steady state strategy are studied in this study.By comparing the leptin concentrations of T.belangeri under different body fat levels,we successfully constructed an animal model of negative correlation between leptin concentrations and body fat levels.Through further research at the adipose tissue and cellular levels,we found that the weight of subcutaneous adipose tissue in the obese group of animals increased significantly,while the weight of adipose tissue in other parts did not show significant changes.This indicates that the increase in adipose tissue in obese animals mainly comes from subcutaneous fat.In addition,from the measurement results of leptin secretion in various parts of adipose tissue,it can be seen that the subcutaneous adipose tissue of obese animals showed a significant decrease in leptin secretion,while the leptin secretion in other parts of adipose tissue was not significantly affected by obesity.Therefore,we have identified subcutaneous adipose tissue as the key site causing a decrease in leptin concentration at the organizational level.Finally,through transcriptome and bisulfite sequencing(BSP)and other technologies,we found that 2876 genes were differentially expressed.Further annotation,enrichment,and key gene screening through the database revealed a significant increase in methyltransferase expression in the obese group of animals.In addition,the sequence alignment results of methylation sequencing showed that multiple sites in the leptin gene promoter region of T.belangeri in the obese group had been methylated.In summary,we have revealed that this "abnormal" secretion is mediated by methylation of the leptin gene in subcutaneous adipose tissue.To understand how animals regulate energy metabolism when leptin concentration is negatively correlated with body fat,we analyzed the metabolomics and energy intake and expenditure characteristics of animals.A total of 34 differential metabolites have been annotated,among which metabolites such as citric acid,pyruvate,and aconitic acid were upregulated in the obese group.Through further annotation and analysis,we found that the upregulated metabolites in the obese group of animals mainly participate in pathways such as glycolysis and tricarboxylic acid cycle,indicating that the energy consumption of subcutaneous adipose tissue in animals increases after obesity.In addition,the 18F-FDG of the obese group of animals ultimately accumulates in a large amount in subcutaneous adipose tissue,which directly confirms that the energy consumption of subcutaneous adipose tissue in T.belangeri does increase after obesity.In addition,as the concentration of leptin decreases,the metabolic rate,BAT weight,and UCP1 protein expression of animals also increase.In summary,the T.belangeri achieves energy balance by increasing energy consumption to offset the increase in intake energy caused by decreased leptin secretion,and the "abnormal" secretion of leptin plays a key role in this process.In conclusion,the study challenged the traditional view that leptin concentration is positively correlated with body fat for a long time,and further revealed the internal molecular mechanism and energetics strategy that leptin is negatively correlated with body fat.This unique leptin secretion mechanism and energy homeostasis strategy expanded our understanding for this field,and broadened our thinking on leptin and animal energetics research in the future.In addition,this study also enriched the cognition of leptin’s mode of action in the body’s energy homeostasis,and provided a possible target for drug development to control the quantitative expression of leptin.