The Roles Of White To Brown Fat Transformation Regulated By BDNF-TrkB In The Energy Metabolism

Objective:1. To investigate the expression of brain-derived neurotrophic factor (BDNF) and precursor of brain-derived neurotrophic factor (pro-BDNF) in human serum. And,analyze the correlation between BDNF, pro-BDNF and obesity.2. To investigate the expression of BDNF in the peripheral tissues.3. To investigate whether BDNF prevent obesity by mediates browning via tyrosine kinase receptor B (TrkB) pathway.Methods:Part1. We conducted the study in a sample of 1598 Chinese adults without any metabolic disease and metabolic related diseases. The survey was randomly collected data from the physical examination population of a hospital from October 2013 to May 2014. According to the BMI, participants were divided to normal group (BMI<24) and obesity group (BMI>24), and then divided as age and sex. BDNF and pro-BDNF serum levels were detected by enzyme-linked immunosorbent assay (ELISA) kits. To explore the correlation between BDNF, pro-BDNF and obesity.Part2. The mice were randomly divided into normal group (fed with normal diet) and model group (fed with high fat diet). After 12 weeks, the model mice weigh more than the average weight of normal group mice by 20% as obese group. The serum level of BDNF was detected by ELISA. Western blotting was used to detect the expression of BDNF in brown adipose fat, white adipose fat and skeletal muscle.Part3. 1. 3T3-L1 fibroblasts induced to mature adipocytes and divided into normal group and BDNF group. BDNF group maintained in complete supplemented with recombinant BDNF protein. Electron microscope was used to observe the cell ultrastructure. Expression of TrkB was dected with Western blotting. 2. 3T3-L1 fibroblasts induced to mature adipocytes and divided into normal group, BDNF group and TrkB (-) group. BDNF group maintained in complete supplemented with recombinant BDNF protein. TrkB (-) group adipocytes was pretreated with TrkB inhibitor for 24h before the administration of BDNF. Detect of brown adipose fat marker (PRDM16) with western blotting.Results:Part1. Serum levels of BDNF were significantly lower (p<0.001) while pro-BDNF(p<0.001) were higher in the obesity compared to the normal group. In the obesity, the serum levels of BDNF were negatively correlated with BMI and pro-BDNF level was positive correlated with BMI. In obese people, the serum level of BDNF and pro-BDNF was no significant difference between male and female. In addition, BDNF levels were substantially lower in the elderly compared to the young (p<0.01) and middle-aged(p<0.001) in obese subjects. In contrast, pro-BDNF levels were higher in the elderly compared to the young and middle-aged (p<0.01) groups.Part2. Body weight, food intake and Lee’s index in obese mice were significantly higher than those in the normal group. The WAT wet weight in obese group was obviousily higher than that in normal group (P<0.01) while BAT wet weight was lowerer in obesity(P<0.01). In serum, the level of BDNF in obesity group was significantly lower than that in the normal group (P<0.05). In WAT, BAT and skeletal muscle, the expression of BDNF was significantly higher in obesity group compared to normal group (P<0.01).Part3. BDNF promoted the lipid droplets from large and aggregate distribution into small and scattered in the distribution. TrkB was expressed in adipocytes and the exogenous BDNF up-regulated the expression of TrkB. The expression of PRDM16 was significantly higher in BDNF group compared to normal group and PRDM 16 expression was lower in TrkB (-) group than BDNF group. The expression of PRDM16 in TrkB (-) group was significantly higher than that in normal group.Conclusions:1. BDNF and pro-BDNF are expressed in human serum. In obese people, BDNF is negatively correlated with BMI and pro-BDNF is positively correlated with BMI.2. The serum BDNF level of obesity was significantly lower than that in normal mice while the expression of BDNF in BAT,WAT and skeletal muscle was significantly higher than that in normal mice. This may be related to the regulation of energy metabolism in the body after obesity. Compensatory increase in energy metabolism related to the organizations of BDNF expression, and then promotes the energy consumption.3. BDNF-TrkB pathway stimulates white to brown fat transformation which mediates energy metabolism.