Effect of calcium signaling by IP3 pathway on the fat deposition of obese mice | 钙信号通过IP3通路对肥胖小鼠脂肪合成代谢的影响

Chinese. 探讨IP3信号通路是否会影响肥胖小鼠细胞内的钙离子浓度以及钙信号对肥胖小鼠脂肪代谢的作用机制，进一步了解胞内钙离子浓度变化对脂肪代谢的作用机理。用高脂日粮饲喂小鼠30 d以建立肥胖模型，将肥胖小鼠分为对照组、去甲肾上腺素(NE)组、肝素组、钙组、钙+NE组和钙+肝素组，除对照组和钙组外的各药物组小鼠分别给予相应的药物处理，腹腔注射质量浓度0.1 mg/mL的NE或1.5 mg/mL的肝素0.2 mL/(只•d)；对照组和钙组同法给予等体积的生理盐水。对照组、NE组和肝素组小鼠饲喂普通日粮，钙组、钙+NE组和钙+肝素组小鼠饲喂加钙饲粮(钙含量12 g/kg)，小鼠共饲喂16 d，期间每3 d测1次体质量，17 d时禁食12 h，摘眼球取血后脱颈椎处死，分离血清检测其中甘油三酯（TG）、总胆固醇(TC)和高密度脂蛋白(HDL-C)的浓度，并取脂肪组织，测定附睾脂肪和肾周脂肪组织质量，分析附睾脂肪、肾周脂肪和肝脏的钙含量。通过RT-PCR法分析与脂肪生成密切相关的转录因子PPARγ、C/EBPα和脂解基因HSL及生脂基因FAS mRNA的表达水平，检测IP3受体IP3R1的mRNA表达水平。肝素和膳食钙处理对肥胖小鼠有极显著的减肥效果(P＜0.01)，可极显著减少体脂质量(P＜0.01)，降低血清中TG和TC浓度(P＜0.01)，而HDL-C浓度极显著升高(P＜0.01)，肝素和膳食钙处理肥胖小鼠的PPARγ、FAS和IP3R1的 mRNA水平均极显著降低(P＜0.01)，HSL mRNA水平极显著升高(P＜0.01)，C/EBPα的mRNA水平无明显变化；NE处理对肥胖小鼠的作用效果与肝素相反，其可明显削弱减肥作用(P＜0.01)。膳食钙有显著的减肥效果(P＜0.01)，但钙+NE组的减肥效果弱于钙组(P＜0.01)，钙+肝素组的减肥效果强于膳食钙的处理效果(P＜0.01)。IP3通路激活可引起胞内钙离子浓度升高，脂肪蓄积增加；反之，脂肪蓄积减少。通过IP3通路，膳食钙可抑制胞内钙离子增加。

English. Intracellular calcium ion concentration has a change under the action of IP3 channel. This study observed what intracellular calcium has on fat metabolism in obese mice so that we could learn more about calcium signaling of intracellular calcium. Obese mice were fed with high-fat diet, treated with norepinephrine, heparin, Calcium carbonate and norepinephrine＋Calcium carbonate, heparin＋Calcium carbonate for 16 days. Mice of norepinephrine, heparin, norepinephrine＋Calcium carbonate, heparin＋Calcium carbonate group were given appropriate medication, by intraperitoneal injection the 0.1 mg/mL NE or 1.5 mg/mL heparin 0.2 mL/(only•d), control group and calcium group were given the same volume of saline. Mice of control group, NE group and Heparin group were fed normal diets, while other groups were fed calcium diets (12 g/kg of calcium content). Mice were fed for 16 d, measured every 3 days. Mice were fasted 12 h on 17 d. The mice were killed after removing the eyes and cervical. Total cholesterol (TC), triglycerides (TG) and high density lipop rotein cholesterol (HDL-C) were measured in Serums. We obtained adipose tissues, weighed adipose tissues, measured the calcium concentration of epididymal fat, perirenal fat and liver. The expression levels of two major transcriptional factors PPARγ and C/EBPα as well as lipolytic gene HSL, lipogenic gene FAS and IP3 receptor IP3R1 mRNA were measured by RT-PCR. The results showed dietary calcium and heparin resulted in extremely significant weight loss and body fat gain decrease(P＜0.01). The content rations of TG and TC in blood serum decreased extremely significantly(P＜0.01), and that of HDL-C increased extremely significantly(P＜0.01). The expression levels of PPARγ, FAS and IP3R1 mRNA were extremely down-regulated(P＜0.01), C/EBPαmRNA levels did not show significant changes, while the expression level of HSL mRNA increased extremely significantly(P＜0.01). NE alone had an extremely significant weight gain on mice(P＜0.01). Dietary calcium had extremely significant weight loss(P＜0.01), norepinephrine＋Calcium carbonate had extremely significant weight loss(P＜0.01), carbonate, heparin＋Calcium carbonate had extremely litter weight loss(P＜0.01). IP3 pathway activation can increase intracellular calcium and fat accumulation; And IP3 pathway suppression reduces fat accumulation. Through the IP3 pathway, dietary calcium can inhibit the increase in intracellular calcium.