Type II iodothyronine 5'-deiodinase and uncoupling protein in brown adipose tissue of human newborns.

Abstract

Brown adipose tissue (BAT) is the major thermogenic organ of the human neonate. To determine whether it is also active in the peripheral conversion of T4 to T3, as shown in several animal species, interscapular BAT from 13 newborns of 25-40 weeks gestational age who survived 4 days, at most, was investigated. BAT was found to contain significant amounts of the mitochondrial uncoupling protein (UCP), the rate-limiting component of heat production. The specific content of UCP increased from 29.4 +/- 3.3 to 62.5 +/- 10.2 pmol/mg protein between 25 and 40 weeks of gestation, respectively, and the UCP/F1-ATPase molar ratio, a sensitive marker of brown fat differentiation, increased similarly. BAT was also found to contain iodothyronine 5'-deiodinase (5'D), which appears to be a type II enzyme, based on high affinity for T4 (Km, 2.9 nmol/L) and insensitivity to propylthiouracil (10% inhibition by 1 nmol/L). 5'D was active by 25 weeks gestation, and the specific activity increased from 116 +/- 15 to 417 +/- 46 fmol/h.mg protein during the period examined. The development of 5'D activity was similar to the changes in UCP content; both exhibited a major increase before 32 weeks gestation. The results indicate that thermogenic function and 5'D activity develop in human BAT rather early, during the first half of the last trimester of gestation. The activities of 5'D in human BAT are comparable with 5'D activities found in animal BAT stimulated during the perinatal period, by cold exposure, or by increased cAMP levels.

Cellular and molecular effects ofn−3 polyunsaturated fatty acids on adipose tissue biology and metabolism

“…During the perinatal period, dynamic recruitment of both BAT and WAT occurs, with important differences among species. Humans are born with substantial amounts of both tissues, with BAT and WAT developing during the last trimester of gestation [61,62]. The amount of BAT declines sharply during the early postnatal period, but it may exist even in the elderly as brown adipocytes interspersed in WAT [63].…”

Subcutaneous fat in normal and diseased states

“…2,25,26 In neonates and newborn children, BAT can be found in several areas, including the interscapular region (shoulder), surrounding blood vessels, muscles in the neck, in the axillae, along the great vessels, trachea, esophagus at the thoracic inlet, and around the abdominal aorta, pancreas, adrenal glands, and kidneys. [26][27][28][29] In small mammals, such as rodents, BAT persists throughout its lifespan.…”

Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement

“…D2 activity in humans has been detected in various tissues, predominantly in the central nervous system, pituitary gland, thyroid, heart, brown adipose tissue and skeletal muscle (15)(16)(17) In healthy adults, D3 expression is found predominantly in the brain and skin (24,25 17 17 observed in individuals with TSH levels >10 mIU/L, with potential effects of TSH values > 7 mIU/L (52). In an additional retrospective study, fewer ischemic heart disease events were associated with treatment of SCH in those under age 70 years (53).…”