Decreased brown adipocyte recruitment and thermogenic capacity in mice with impaired peroxisome proliferator-activated receptor (P465L PPARγ) function
Decreased brown adipocyte recruitment and thermogenic capacity in mice with impaired peroxisome proliferator-activated receptor (P465L PPARγ) function
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DOI：
10.1210/en.2006-0684
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发表时间：
2006-12-01
期刊：
影响因子：
4.8
通讯作者：
Vidal-Puig, Antonio
中科院分区：
文献类型：
--
作者：
Gray, Sarah L.;Nora, Edoardo Dalla;Vidal-Puig, Antonio
具有显性负性过氧化物酶体增殖物激活受体γ（PPARgamma）突变（P465L）的小鼠出人意料地具有正常量的脂肪组织。在这里，我们调查的脂肪组织的PPAR γ P465L小鼠的详细信息。P465L PPAR γ小鼠肩胛间脂肪组织的显微镜分析显示棕色脂肪细胞具有较大的单室脂滴，表明产热能力降低。在冷暴露条件下，PPARgamma P465L小鼠的棕色脂肪组织活性较低，这一事实反映在解偶联蛋白1水平降低。对白色脂肪细胞的分析证实了它们的正常细胞结构和发育，然而P465 L PPAR γ小鼠的经典白色脂肪库在棕色脂肪细胞募集方面显著减少，这一发现得到了性腺周围脂肪库中UCP 1表达减少的支持。综上所述，这些数据表明，整个动物的过氧化物酶体增殖物激活物受体γ损伤改变了脂肪器官的细胞组成，使脂肪表型更“白白色”。从生理学上讲，这种棕色脂肪细胞募集的损伤与冷适应后非颤抖性产热能力的降低有关，这一点由去甲肾上腺素反应性所揭示。我们的研究结果表明，维持氧化棕色样脂肪组织是更依赖于过氧化物酶体增殖物激活受体γ功能的发展比白色脂肪组织，观察时，可能是相关的考虑过氧化物酶体增殖物激活物γ依赖的策略治疗肥胖症。
Mice with a dominant-negative peroxisome proliferator-activated receptor gamma(PPAR gamma) mutation (P465L) unexpectedly had normal amounts of adipose tissue. Here, we investigate the adipose tissue of the PPAR gamma P465L mouse in detail. Microscopic analysis of interscapular adipose tissue of P465L PPAR gamma mice revealed brown adipocytes with larger unilocular lipid droplets, indicative of reduced thermogenic capacity. Under conditions of cold exposure, the brown adipose tissue of the PPAR gamma P465L mice was less active, a fact reflected in decreased uncoupling protein 1 levels. Analysis of the white adipocytes confirmed their normal cytoarchitecture and development, yet classical white adipose depots of the P465L PPAR gamma mice had a striking reduction in brown adipocyte recruitment, a finding supported by reduced expression of UCP1 in the perigonadal adipose depot. Taken together, these data suggest that whole animal impairment of PPAR gamma alters the cellular composition of the adipose organ to a more "white" adipose phenotype. Physiologically, this impairment in brown adipocyte recruitment is associated with decreased nonshivering thermogenic capacity after cold acclimation as revealed by norepinephrine responsiveness. Our results indicate that maintenance of oxidative brown-like adipose tissue is more dependent on PPAR gamma function for development than white adipose tissue, an observation that may be relevant when considering PPAR gamma-dependent strategies for the treatment of obesity.