Giacobino J P, Moinat M, Muzzin P, Siegrist-Kaiser C A, Seydoux J, Girardier L
Department of Medical Biochemistry, Centre Médical Universitaire, Geneva, Switzerland.
Mol Cell Endocrinol. 1989 Feb;61(2):217-25. doi: 10.1016/0303-7207(89)90133-0.
The induction of hypothyroidism in rats by methimazole affects interscapular brown adipose tissue (IBAT) mitochondrial and peroxisomal enzyme activities in opposite directions. Hypothyroidism, indeed, decreases both mitochondrial succinate dehydrogenase and beta-oxidation total activities by 35 and 45%, respectively and increases peroxisomal catalase and acyl coenzyme A (acyl CoA) oxidase total activities 3.2- and 1.6-fold, respectively. Administration of a thyroid hormone analogue (3'-isopropyl-3,5-diiodo-L-thyronine) prevents these enzymatic modifications. The effects of hypothyroidism on IBAT mitochondrial enzyme activities seem to be direct, i.e. due to the lack of thyroid hormones, while those on peroxisomal enzyme activities might be indirect, i.e. secondary to the increased thermogenic needs of the rat and mediated by adrenergic stimulation. It is noteworthy that the indirect effects of hypothyroidism on peroxisomes are not observed in liver where acyl CoA oxidase activity is in fact decreased by 40%. In hypothyroid rat IBAT, administration of the peroxisome proliferator nafenopin does not further stimulate the already increased peroxisomal enzyme activities and does not inhibit the already decreased mitochondrial enzyme activities.
甲巯咪唑诱导大鼠甲状腺功能减退会对肩胛间棕色脂肪组织(IBAT)的线粒体和过氧化物酶体酶活性产生相反的影响。事实上,甲状腺功能减退分别使线粒体琥珀酸脱氢酶和β-氧化总活性降低35%和45%,而过氧化物酶体过氧化氢酶和酰基辅酶A(酰基辅酶A)氧化酶总活性分别增加3.2倍和1.6倍。给予甲状腺激素类似物(3'-异丙基-3,5-二碘-L-甲状腺原氨酸)可防止这些酶的改变。甲状腺功能减退对IBAT线粒体酶活性的影响似乎是直接的,即由于缺乏甲状腺激素,而对过氧化物酶体酶活性的影响可能是间接的,即继发于大鼠产热需求的增加并由肾上腺素能刺激介导。值得注意的是,甲状腺功能减退对过氧化物酶体的间接影响在肝脏中未观察到,在肝脏中酰基辅酶A氧化酶活性实际上降低了40%。在甲状腺功能减退的大鼠IBAT中,给予过氧化物酶体增殖剂萘芬诺平不会进一步刺激已经升高的过氧化物酶体酶活性,也不会抑制已经降低的线粒体酶活性。