Science brown fat that is activated by the cold and the one that is turned on by overeating, although recent findings suggest that these functions are not completely identical. Both are controlled, at least in part, by the sympathetic nervous system. In particular, catecholamines such as norepinephrine released from nerve endings on brown fat cells stimulate the cells to oxidize substrates more rapidly, producing heat. Injection of norepinephrine increases heat production, and treatment with drugs that block catecholamine receptors blocks it. Recently Stock has shown that the initial signal to release norepinephrine comes from the region of the brain called the ventromedial hypothalamus—a region that also plays a role in appetite control. Lesions in this part of the brain result in obese rats, and electrical stimulation causes an increase in brown fat thermogenésis. This signal is sensitive to insulin levels, suggesting that insulin may be the sensor that causes the ventromedial hypothalamus to trigger norepinephrine release, at least in overfed animals. How important this brown fat system is in adult humans is not well known, but there are some data that suggest it may play a role in weight regulation. Stock and others have administered norepinephrine to humans and found increases in skin temperature in the back of the neck and along the backbone—the regions where brown fat deposits are found in adults. The effect is reduced in obese women, suggesting that they, like obese rats, may have a defect in their ability to switch on this mechanism for maintaining constant body weight. However, how great a role such a system may play in humans is uncertain. Some autopsies of adults do not find any brown fat deposits. Proponents of the tissue's importance suggest that the pathologists simply were not looking hard enough for brown fat or that the cells sometimes are distributed in such small colonies in ordinary white fat that they are not easily seen. In any case, more reliable estimates of how much of this tissue exists in adults will be needed before its importance in weight control can be pinned down. What happens in the mitochondria of brown fat cells once norepinephrine is released has been fairly well worked out by Nicholls and HimmsHagen. The mitochondria of normally functioning brown fat cells are unique in that they can be made permeable to protons. This permeability is con26
C&ENFeb. 16, 1981
trolled by a polypeptide of molecular weight of about 32,000 daltons that is the major constituent of the mitochondria's inner membrane. Purine nucleotides can bind to this polypeptide. When they are bound, the membrane is impermeable to protons; when they are not bound the membrane is permeable. When protons can enter the mitochondrion they disrupt the ordinary oxidation-oxidative phosphorylation cycle of this body. In most mitochondria oxidative phosphorylation is coupled to oxidation by means of a proton pump. When the mitochondria's membranes admit protons, however, these processes come uncoupled, so that oxidation can lead directly to heat production, bypassing production of adenosine triphosphate. This effect can be seen dramatically in the differences between genetically obese and normal mice as they adapt to the cold. Electron micrographs of their respective mitochondria show a greater degree of
organization in the lean mice, even at normal laboratory temperatures. Exposing the animals to the cold accentuates this difference; mitochondria of the lean mice become even more structured and develop a characteristic, tightly banded pattern which allows their enzymes to function more efficiently. The mitochondria from obese mice change very little. Although the effects on brown fat of overfeeding and exposure to the cold are very similar, they appear to have some differences. Recent work in Himms-Hagen's laboratory shows that the cold-acclimated animal not only increases the amount of brown fat tissue it possesses, as overfed animals do; cold adaptation also causes changes in the mitochondria themselves that are not found in overfed animals. One that may be important is that the amount of the 32,000molecular-weight polypeptide increases. What this change may mean for the animal is not yet clear. Rebecca Rawls, Washington
Brassinolide analogs promote plant growth Synthetic analogs of the naturally occurring plant growth promoter brassinolide show varying levels of plant growth-promoting activity themselves and could have commercial applications for increasing crop yields, N. Bhushan Mandava told the American Chemical Society's recent Middle Atlantic Regional Meeting in Washington, D.C. Brassinolide, chemically 2α,3α,22(Λ), 23(i?)-tetrahydroxy-24(S)methyl-B-homo-7-oxa-5û! -choies tan-6-one, is a steroid that was isolated from the pollen of the rape plant and characterized by mass spectrometry and x-ray analysis by researchers headed by Michael D. Grove and Mandava, both with the Department of Agriculture. The compound, which contains a sevenatom B-ring lactone unprecedented OH H
C
HCK^
A HCK'
CH3
3^ ^^23^X / CH 3 T A I
Êr Β
)
\ ^ \ _ o Η Ο
Brassinolide
!
in a natural steroid, promotes both cell elongation and cell division in several plant bioassays. Malcolm J. Thompson, also with USDA, and Mandava synthesized two brassinosteroids that differ from brassinolide only in the stereochem istry of the 22- and 23-hydroxyl groups and the 24-methyl group. Both showed plant growth-promoting activity. They also synthesized iso meric mixtures of homobrassinolide, in which the 24-methyl group is re placed with an ethyl group, and norbrassinolide, in which the 24-methyl group is replaced with a hydrogen atom. Again, both compounds pro moted plant growth in the bioas says. Unlike growth promoters such as gibberellic acid, which stimulates only cell elongation, Mandava says, the brassinosteroids promote both cell elongation and cell division leading to increased biomass. When tested on several vegetable crocs, the brassi nosteroids increased crop yield 5 to 54% depending on crop and soil con ditions. The brassinosteroids also act at much lower concentrations than other growth promoters. For the field tests, the researchers used a 1-ppm solution of brassino steroids with emulsifiers and water. Mandava estimates that crops could be treated with such solutions for about $5.00 to $10 per acre. D
