低强度脉冲超声对食源性肥胖小鼠脂肪细胞肥大的作用及机制研究

Low-intensity pulsed ultrasound attenuates hypertrophy of local adipocytes in diet-induced-obese mice

目的:探究低强度脉冲超声(low-intensity pulsed ultrasound,LIPUS)对食源性肥胖小鼠脂肪细胞肥大的影响及分子机制。方法:C57BL/6J雄性小鼠食用60%kcal脂肪的高脂饲料进行肥胖小鼠造模,肥胖小鼠接受10周腹股沟脂肪垫LIPUS辐照。称量小鼠及靶区脂肪重量;抽取外周静脉血检测血脂、血常规和血生化;超声波穿透路径组织(皮肤、肌肉)HE染色评估LIPUS的体内安全性;靶区脂肪HE染色观察脂肪细胞大小;甘油磷酸氧化酶-过氧化物酶法测定靶区脂肪内甘油三酯含量;qPCR分析靶区脂肪成脂分化转录因子、脂解酶及其转录因子的表达;Western blot检测成脂分化转录因子、脂解酶和脂解相关信号通路的蛋白水平。结果:当声强达到77.20 mW/cm^(2)时,LIPUS辐照明显降低肥胖小鼠靶区脂肪重量,甘油三酯含量减少,脂肪细胞体积减小。同时,LIPUS下调靶区脂肪成脂分化转录因子的表达,激活脂解相关信号通路,上调脂解酶的表达水平。此外,初步结果表明LIPUS在该治疗剂量下具有良好的安全性。结论:LIPUS通过降低成脂分化转录因子表达,提高脂解水平,改善肥胖小鼠脂肪细胞肥大。

Objective:The aim of this study was to investigate the potential effects and mechanisms of low-intensity pulsed ultrasound(LIPUS)on the metabolism of hypertrophic adipose tissue induced by high-fat diet.Methods:C57BL/6J male mice were fed with a high-fat diet containing 60%kcal fat for obese mice model,and then 10 obese mice were selected to receive LIPUS irradiation at the groin fat pad for 10 weeks.The body weight of mice and inguinal fat at target area were weighed.Peripheral venous blood was drawn for the blood lipid test,complete blood counts and plasma biochemical profile.Safety tests of LIPUS were conducted on the basis of skin and muscle sections at LIPUS site with HE staining.And target fat stained with HE was used to observe the size of adipocytes.The content of triglycerides in the target fat pad was measured by glycerol phosphate oxidase-p-aminophenazone methods.The mRNA expression levels of transcription factors for adipogenic differentiation,lipolytic enzymes and their transcription factors at the LIPUS region were analyzed by qPCR.Additionally,Western blot was applied to detect the protein levels of transcription factors for adipogenic differentiation,lipolytic enzymes,and their related signaling pathways.Results:LIPUS irradiation significantly reduced fat weight,triglyceride content and adipocyte size in the target area of obese mice that received 77.20 mW/cm^(2) LIPUS treatment.Meanwhile,LIPUS down-regulated the expression of transcription factors for adipogenic differentiation in the target region.Expressions of lipolysis related signaling pathways and lipolytic enzymes were up-regulated via LIPUS stimulation.In addition,preliminary results indicate that LIPUS has a good safety profile at current dose.Conclusion:LIPUS diminishes local adipose tissue hypertrophy induced by high-fat diet through inhibiting adipogenic differentiation and encouraging lipolysis procedure.