Hypothyroidism was induced in adult rats by oral absorption of methimazole and its effects on brown adipose tissue (BAT) were studied. Hypothyroidism partially mimicked the effects of chronic exposure to cold: BAT weight and its DNA content were increased and the mitochondrial components (proteins, phospholipids) of the tissue were greatly enhanced when expressed per unit of fresh tissue weight. Moreover, hypothyroidism had the same effects as adaptation to cold on the fatty-acid composition of both total and mitochondrial phospholipids. Basal respiratory rate and total cytochrome C oxidase activity of the tissue were also increased. However, the increase in the concentration of the '32,000 mol. wt protein', a polypeptide which regulates the dissipation of heat by BAT, was smaller and non-selective in hypothyroid rats. The amount of this protein was increased per mg tissue, but not per mg mitochondrial proteins, as in rats adapted to cold. Furthermore, in contrast with the large mobilization of the lipid stores in BAT of euthyroid animals, the BAT lipid stores of hypothyroid rats were not mobilized during the first hours of exposure to cold. It may be concluded that (a) hypothyroidism induces several alterations in BAT which are characteristic of an active thermogenic state (this may be because of the response of the organism to the deficiency of thermogenesis induced by hypothyroidism), (b) this potential increase in thermogenic capacity in the BAT of hypothyroid rats has probably a limited physiological role, since thyroid hormones are necessary for the mobilization of the tissue lipids which are the fuel for production of heat and (c) these data provide evidence for a limited role of thyroid hormones in the tropic response of BAT during adaptation to cold.

(1) The effects of cold adaptation upon the brown adipose tissue have been studied in rats, hamsters, mice, and guinea pigs. (2) Striking effects were found for total tissue as well as at the mitochondrial level, e.g., increases in protein and phospholipid contents, changes in phospholipid fatty acid composition (a decrease in the percentage of palmitic and palmitoleic acids and an increase in stearic and linoleic acids), and a change in the mitochondrial polypeptide composition (a marked increase in a 32000 molecular weight polypeptide, except for hamsters). (3) In situations where animals exhibit a greatly enhanced capacity for nonshivering thermogenesis (cold adaptation for rats, mice, and guinea pigs, birth for guinea pigs, and hibernation ability for hamsters, dormice, and garden dormice), brown fat mitochondria are characterized by the occurrence of large amounts of the 32000 molecular weight polypeptide characteristic of these mitochondria.

The heparin-releasable LP lipase activity of BAT (brown adipose tissue), and the TG (triglyceride) content of plasma were determined in normal and hypothyroid rats during early post-natal development. The TG content of plasma increased sharply after the onset of suckling and decreased during the weaning period in normal rats, while it stayed at a high level in hypothyroid rats. LP lipase activity was maximal during the perinatal period and decreased later, being practically undetectable in one month old control animals; in contrast, LP lipase activity was still present in cretin rats at this age. The effects of several forms of treatment were also tested in weaned rats: a high-fat diet was not able to maintain the high LP lipase activity of suckling rats, but the activity was high if the animals were bred at a cold temperature. Thyroxine injections had no effect. These results are discussed in terms of the possible factors regulating the LP lipase activity in BAT.

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