Abnormal brown adipose tissue in obese (ob/ob) mice: response to acclimation to cold.
Abnormal brown adipose tissue in obese (ob/ob) mice: response to acclimation to cold.
复制标题
肥胖（ob/ob）小鼠的异常棕色脂肪组织：对寒冷适应的反应。
DOI：
10.1152/ajpendo.1980.239.4.e301
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发表时间：
1980
期刊：
影响因子：
--
通讯作者：
J. Himms‐Hagen
中科院分区：
文献类型：
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作者：
S. Hogan;J. Himms‐Hagen
霍根，苏珊，和简·海姆-哈根。肥胖（ob/ob）小鼠中的异常棕色脂肪组织：对coZd适应的反应。Am. J. Physiol.239（Endocrinol. Metab. 2）：E301-E309，1980年。遗传性肥胖（ob/ob）小鼠棕色脂肪组织线粒体具有异常的超微结构和低嘌呤核苷酸结合，线粒体膜的多肽组成相对正常。已知嘌呤核苷酸与分子量为32，000的多肽上的特定位点结合，该位点与棕色脂肪组织线粒体的产热质子传导途径相关。这些位点似乎在ob/ob小鼠中被掩蔽。ob/ob小鼠暴露于寒冷（4 C）既不增加嘌呤核苷酸的结合，也不改变线粒体的超微结构，就像瘦小鼠一样。使肥胖小鼠适应轻度寒冷（14 ℃）（已知可提高其抗寒性）可诱导几乎正常的组织生长、线粒体增殖和线粒体性质的改变（嘌呤核苷酸结合增加; 32，000区域的多肽比例增加;更正常的超微结构）。它的结论是，棕色脂肪组织线粒体的缺陷是一个贡献的原因，已知的缺陷nonshriving产热在ob/ob小鼠，因此在这种动物的肥胖。缺陷似乎是在开关机制，介导的去甲肾上腺素，允许急性产热反应冷。在适应轻度寒冷期间允许组织生长和改善线粒体产热功能的适应机制是正常的，并且可以解释已知的冷适应ob/ob小鼠的产热能力改善。肥胖症;去甲肾上腺素;线粒体;非颤抖性产热基因肥胖小鼠（ob/ob）长期以来被认为对寒冷非常敏感，这显然是由于产热功能的缺失（4）。在4 ℃时，仅在氧摄取短暂增加后（3l），肥胖小鼠逐渐体温降低，并在约3小时内死亡（4，31）。肥胖小鼠在除热中性（小鼠为30-33 ℃）外的所有温度下的静息代谢率（2，31）和体温（31）均低于瘦小鼠。产热缺陷在发育早期就很明显，在5-12日龄时可通过较低的静息代谢率（2，17）、较低的体温（16，32）以及暴露于轻度寒冷（15 ℃）时体温下降更快（32）检测到。缺陷的出现与较大比例的体脂肪（30）的初始出现相一致，并且先于食欲亢进（23）。
HOGAN, SUSAN, ANDJEANHIMMS-HAGEN. AbnormaLbrown adipose tissue in obese (ob/ob) mice: response to acclimation to coZd. Am. J. Physiol. 239 (Endocrinol. Metab. 2): E301-E309, 1980.-Brown adipose tissue mitochondria of the genetically obese (ob/ob) mouse have abnormal ultrastructure and low binding of purine nucleotides; polypeptide composition of the mitochondrial membranes is relatively normal. Binding of purine nucleotides is known to be to a specific site on a polypeptide, of molecular weight 32,000, associated with the thermogenic proton conductance pathway of brown adipose tissue mitochondria. These sites appear to be masked in the ob/ob mouse. Exposure of the ob/ob mouse to cold (4 C) neither increases the binding of purine nucleotides nor changes the ultrastructure of the mitochondria, as it does in lean mice. Acclimation of obese mice to mild cold (14” C), known to improve their cold resistance, induces an almost normal tissue growth, mitochondrial proliferation, and alteration in mitochondrial properties (increase in binding of purine nucleotides; increase in proportion of polypeptides in the region of 32,000; more normal ultrastructure). It is concluded that a defect in brown adipose tissue mitochondria is a contributory cause of the known defect in nonshivering thermogenesis in the ob/ob mouse and thus of obesity in this animal. The defect appears to be in the switching mechanism, mediated by noradrenaline, that allows an acute thermogenic response to cold. The adaptive mechanism that allows tissue growth and improvement of mi-tochondrial thermogenic function during acclimation to mild cold is normal and can account for the known improved thermogenic capacity of cold-acclimated ob/ob mice. obesity; noradrenaline; mitochondria; nonshivering thermogenesisTHE GENETICALLY OBESE MOUSE (ob/ob) has long been known to be remarkably susceptible to cold, apparently because of a failure of thermogenesis (4). At 4 C after only a transient increase in oxygen uptake (3l), the obese mouse becomes progressively hypothermic and dies in about 3 h (4, 31). The obese mouse has a lower resting metabolic rate (2, 31) and a lower body temperature (31) than the lean mouse at all temperatures except at thermoneutrality (30-33 C for the mouse). The defect in thermogenesis is apparent very early in development, being detectable at 5-12 days of age by the lower resting metabolic rate (2, 17), the lower body temperature (16, 32), and the more rapid decrease in body temperature during exposure to mild cold (15 C)(32). The appearance of the defect coincides with the initial appearance of a larger proportion of body fat (30) and precedes the hyperphagia (23).