Methylation of the leptin gene promoter is associated with a negative correlation between leptin concentration and body fat in Tupaia belangeri.

AIMS: Leptin is a signaling protein secreted by white adipose tissue encoded by the obesity gene, and its main function is to regulate the food intake and energy metabolism in mammals. Previous studies had found that animal leptin concentration was positively correlated with its body fat, but the leptin concentration of Tupaia belangeri was negatively correlated with its body fat mass. The present study attempted to investigate the mechanisms of leptin concentration negatively correlated with its body fat mass in T. belangeri. MATERIAL AND METHODS: We measured the leptin concentration of the two groups of animals by enzyme linked immunosorbent assay (ELISA) and quantified the leptin mRNA expression by qPCR. Then, the histological, transcriptomic, and bisulfite sequencing of the two groups of animals were studied. Moreover, to investigate the energy metabolism under the negative correlation, we also analyzed the metabolomics and metabolic rate in T. belangeri. KEY FINDINGS: We revealed the negative correlation was mediated by leptin gene methylation of subcutaneous adipose tissue. Further, we also found that T. belangeri increased energy metabolism with leptin decreased. SIGNIFICANCE: We challenge the traditional view that leptin concentration was positively correlated with body fat mass, and further revealed its molecular mechanism and energy metabolism strategy. This special leptin secretion mechanism and energy metabolism strategy enriched our understanding of energy metabolism of animals, which provided an opportunity for the clinical transformation of metabolic diseases.

Differences of energy adaptation strategies in Tupaia belangeri between Pianma and Tengchong region by metabolomics of liver: Role of warmer temperature.

Global warming is becoming the future climate trend and will have a significant impact on small mammals, and they will also adapt at the physiological levels in response to climate change, among which the adaptation of energetics is the key to their survival. In order to investigate the physiological adaptation strategies in Tupaia belangeri affected by the climate change and to predict their possible fate under future global warming, we designed a metabonomic study in T. belangeri between two different places, including Pianma (PM, annual average temperature 15.01°C) and Tengchong (TC, annual average temperature 20.32°C), to analyze the differences of liver metabolite. Moreover, the changes of resting metabolic rate, body temperature, uncoupling protein 1content (UCP1) and other energy indicators in T. belangeri between the two places were also measured. The results showed that T. belangeri in warm areas (TC) reduced the concentrations of energy metabolites in the liver, such as pyruvic acid, fructose 6-phosphate, citric acid, malic acid, fumaric acid etc., so their energy metabolism intensity was also reduced, indicating that important energy metabolism pathway of glycolysis and tricarboxylic acid cycle (TCA) pathway reduced in T. belangeri from warmer habitat. Furthermore, brown adipose tissue (BAT) mass, UCP1 content and RMR in TC also decreased significantly, but their body temperature increased. All of the results suggested that T. belangeri adapt to the impact of warm temperature by reducing energy expenditure and increasing body temperature. In conclusion, our research had broadened our understanding of the physiological adaptation strategies to cope with climate change, and also provided a preliminary insight into the fate of T. belangeri for the future global warming climate.