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J Himms-Hagen

Publications and source records attributed to J Himms-Hagen.

15 recordsLinked to original sources
PubMed1992

ATPase-inhibitor proteins of brown-adipose-tissue mitochondria from warm- and cold-acclimated rats.

1. A group of male Sprague-Dawley rats (5-6 weeks old) was cold-acclimated at 4 degrees C for 4 weeks. Warm-acclimated controls remained at 24 degrees C. Total protein content of brown adipose tissue (BAT) increased more than 3-fold and total uncoupling protein (UCP) content increased more than 6-fold upon cold-acclimation. The concentration of UCP in isolated BAT mitochondria almost doubled. 2. Specific ATPase activity of the non-thermogenic BAT mitochondria (from warm-acclimated controls) was low and increased about 6-fold on addition of 1 microM-Ca2+, which raised free Ca2+ levels (measured by Fura-2) in the incubation media from 1.32 +/- 0.28 microM (mean +/- S.E.M.) to 2.29 +/- 0.39 microM [at which the Ca(2+)-binding ATPase-inhibitor protein (CaBI) is inactivated]. Correspondingly, the specific ATP synthetase activity of the non-thermogenic BAT mitochondria was high and was decreased by 74% by addition of 1 microM-Ca2+. 3. In contrast, specific ATPase activity of thermogenic BAT mitochondria (from cold-acclimated rats) was 5 times that of the control group, and addition of Ca2+ had only a small stimulatory response. Correspondingly, the specific ATP synthetase activity of the thermogenic BAT mitochondria was low, and the decrease by Ca2+ was small, albeit significant. 4. Extracts of BAT mitochondria from both groups of animals contained significant amounts of the ATPase-inhibitor protein of Pullman and Monroy (PMI) as well as of CaBI, as shown by gel electrophoresis. Kinetic studies of inhibition of mitochondrial ATPase activity showed that PMI activity was unaltered in extracts from the thermogenic BAT mitochondria, whereas CaBI activity was slightly but significantly increased. 5. The presence of active ATPase-inhibitor proteins in BAT mitochondria was shown for the first time. We conclude that uncoupling of oxidative phosphorylation occurs in thermogenic BAT mitochondria, even in the presence of the ATPase-inhibitor proteins.

Adenosine Triphosphatases↗
PubMed1992

Rapid but transient atrophy of brown adipose tissue in capsaicin-desensitized rats.

Our previous studies showed atrophy of brown adipose tissue (BAT) in capsaicin-desensitized rats during the period 11-28 days after injections [Cui et al., Am. J. Physiol. 259 (Regulatory Integrative Comp. Physiol. 28): R324-R332, 1990]. The objective of the present studies was to assess the rapidity with which the atrophy occurred and the extent to which recovery had occurred by 8 wk. Rats, either vehicle-injected controls or capsaicin injected, were studied 1, 3, 14, 28, and 52 days after the last injection. BAT was markedly atrophied at 1 day, having less total protein, fewer mitochondria (less total cytochrome oxidase and total uncoupling protein), and fewer cells (less DNA). Atrophy persisted for up to 14 days but had largely disappeared by 28-52 days. A transient reduction in body weight gain and white epididymal adipose tissue weight had also reversed by 28-52 days. We suggest that the rapid atrophy of BAT after capsaicin desensitization is secondary to the loss of sensory neuropeptides in its sensory nerves, neuropeptides that either exert a trophic effect on synthesis of mitochondria or an inhibitory influence on processes that promote degradation of mitochondria. The retardation of the normal age-associated increase in DNA content of BAT in the capsaicin-desensitized rat suggests that sensory neuropeptides might also modulate cell proliferation.

Acclimatization↗
PubMed1992

Long-term decrease in body fat and in brown adipose tissue in capsaicin-desensitized rats.

Previous studies showed that atrophy of brown adipose tissue (BAT) of capsaicin-desensitized rats occurs rapidly and persists for up to 28 days. The rats do not, however, become any more obese than control rats, despite the frequent association of atrophied BAT with obesity. The objective of the present study was to assess longer-term effects of capsaicin desensitization on BAT and on energy balance. Rats were studied at 2.5, 3.5, and 8 mo after treatment. Major effects at 8 mo, mostly seen to a lesser extent at 3.5 mo but not at 2.5 mo, were a marked reduction in body weight that was largely attributable to a reduction in body fat but also to some stunting of growth and an atrophy or lack of growth of BAT (reduced weight and content of protein, DNA, cytochrome oxidase, and uncoupling protein). Resting metabolic rates and food intake at 8 mo were reduced in proportion to the smaller body size. We suggest that the lack of trophic influence of sensory neuropeptides on BAT proposed previously may extend to other organs, including white adipose tissue, and contribute to the reduced adiposity and the smaller body size of capsaicin-desensitized rats.

Adipose Tissue↗
PubMed1992

Effects of cold acclimation and fasting on thyroxine 5'-deiodinase in brown adipose tissue of ob/ob mice.

Gradual acclimation to mild cold for 6 weeks increases the total activity of thyroxine 5'-deiodinase in brown adipose tissue (BAT) of genetically obese (ob/ob) mice to a level greater than that in similarly acclimated lean mice. This increase is largely due to the growth of the BAT in the ob/ob mouse, because specific activity of the enzyme is only slightly increased. In similarly cold-acclimated lean mice, the specific activity of thyroxine 5'-deiodinase was not altered. BAT mitochondrial GDP binding increased to the same high level in the gradually cold-acclimated ob/ob mouse as in cold-acclimated lean mice. We conclude that the growth and maintenance of BAT in the cold-acclimated ob/ob mouse, as in the cold-acclimated lean mouse, does not require greatly increased activity of thyroxine 5'-deiodinase. Fasting for 48 hr did not alter thyroxine 5'-deiodinase activity of BAT in either lean or ob/ob mice. The fasting-induced increase in activity seen by others in lean mice is probably due to thermoregulatory stimulation of BAT occasioned by the low environmental temperature at which the fasting occurred.

Acclimatization↗
PubMed1992

Number of mice per cage influences uncoupling protein content of brown adipose tissue.

The effect of housing density of mice on the thermogenic state and capacity of their brown adipose tissue was studied. Mice were housed one, two, or six per cage at 28 degrees C for 15 days. Increased housing density suppressed the thermogenic capacity of brown adipose tissue (decreased the total amount of uncoupling protein) and decreased the thermogenic state of brown adipose tissue mitochondria (decreased GDP binding). A density of six mice per cage had a greater effect than a density of two mice per cage. The size of brown adipose tissue (wet weight and protein content), the content of mitochondria in it (cytochrome oxidase content), and the total activity of thyroxine 5'-deiodinase were not altered by housing density. We conclude that even at a temperature close to thermoneutrality (29-33 degrees C for the mouse), the occurrence of social thermoregulation (huddling) reduces the requirement for brown adipose tissue thermogenesis and results in a reduction in its thermogenic capacity. It is clearly of importance that the design of studies of mouse brown adipose tissue take into account not only the temperature at which the mice are housed, but also the number of mice housed per cage.

Adipose Tissue, Brown↗
PubMed1979

Obesity may be due to a malfunctioning of brown fat.

Recent basic research on the functioning of brown fat, a heat-producing tissue, has been fitted together with research on obesity to provide an exciting and challenging new approach to the study of the cause of obesity and could serve as a starting point for the development of new modes of treatment. Recent studies on brown adipose tissue have shown that a defect in this tissue is one probable cause of obesity.

Adipose Tissue↗
PubMed1978

Thermogenic mechanisms and their control.

The alterations in properties of mitochondria and of plasma membrane of brown adipose tissue and skeletal muscle of cold-acclimated rats are reviewed in order to bring out any adaptive changes which are related to the mechanism of nonshivering thermogenesis, and thus to the enhanced calorigenic action of catecholamines known to exist in these animals. Since prevention of the morphological changes in the mitochondria by treatment of the animals with oxytetracycline during acclimation to cold also prevents the development of the enhanced calorigenic response to the catecholamines it is concluded that the changes noted are either a cause of the development of the increased capacity for nonshivering thermogenesis during acclimation to cold or are secondary to the operation of nonshivering thermogenesis.

Acclimatization↗
PubMed1978

Increased purine nucleotide binding, altered polypeptide composition, and thermogenesis in brown adipose tissue mitochondria of cold-acclimated rats.

Rapid increases in atractyloside-insensitive binding of purine nucleotides (ADP or GDP) and in a polypeptide of 32 000 occur in brown adipose tissue mitochondria of the rat during acclimation to cold. The increased binding is apparent within 1 h and reaches a maximum after 3--7 days of exposure to 4 degrees C. The increase in the 32 000 peptide occurs more slowly and reaches a maximum after 2--3 weeks. There is a simultaneous decrease in a polypeptide of 96 000, apparent after 1 day and reaching a maximum after 1--2 weeks. Results are interpreted in terms of the appearance of an increased amount of the purine nucleotide-sensitive proton conductance pathway in association with the development of an enhanced thermogenic capacity of brown adipose tissue mitochondria during acclimation of the rat to cold.

Acclimatization↗
PubMed1978

Increased calcium uptake by muscle mitochondria of cold-acclimated rats.

Skeletal muscle mitochondria of cold-acclimated rats have an altered morphology that is related to the occurrence of nonshivering thermogenesis. The transport of calcium by these mitochondria was studied in a search for an alteration in an energy-dissipating mechanism which might be related to the altered morphology and to the altered mode of thermogenesis in the cold-acclimated animal. The rates of calcium uptake, of calcium-stimulated respiration, and of state 4 respiration after calcium uptake were increased in the altered mitochondria. The capacity to accumulate calcium without phosphate was increased, whereas with phosphate all the calcium was removed from the medium and no difference in total uptake was seen. Spontaneous release of calcium was greater but sodium-induced release was unchanged. No effect of cyclic AMP or prostaglandin E1 on release of calcium was seen. The increase in rate of calcium uptake occurred gradually during the first 3-5 wk of acclimation to cold. The results are considered to give some support to the hypothesis that adaptive changes in the mitochondrial calcium transport cycle in skeletal muscle occur during acclimation to cold.

Acclimatization↗
PubMed1976

Monamine oxidase in outer membrane of skeletal muscle mitochondria.

(1) Monoamine oxidase (EC 1.4.3.4) is present in rat skeletal muscle mitochondria. (2) A radioassay procedure for the assay of monoamine oxidase in muscle mitochondria is described. It is based on teh procedure using side-chain [2-14C]-tryptamine as substate described by Wurtman, R.J. and Axelrod, J. (1963) Biochem. Pharmacol. 12, 1439--1441 and employs a pH of 8.0 and a substrate concentration of 0.25 mM. (3) The Km of the muscle mitochondrial enzyme at pH 8.0 is 1.34 - 10(-5) M and that of the liver enzyme under the same conditions is 2.5 - 10(-5) M. Muscle mitochondria contain only one quarter of the activity of enzyme present in liver mitochondria. (4) Monoamine oxidase is shown to be in the outer membrane of skeletal muscle mitochondria and thus to be a suitable marker enzyme for use in the fractionation of these mitochondria.

Animals↗
PubMed1976

Alterations of mitochondrial protein metabolism in liver, brown adipose tissue and skeletal muscle. During cold-acclimation.

Incorporation of L-[U-14C] leucine into liver, brown adipose tissue and skeletal muscle mitochondrial proteins was determined in vivo and in vitro during cold-acclimation. Major alterations in mitochondrial protein metabolism were observed in brown adipose tissue and skeletal muscle but not in liver. Immediate cold-exposure is accompanied by an inhibition of the in vivo incorporation of L-[U-14C] leucine into mitochondrial proteins of all tissues. However, during cold-acclimation the incorporation of leucine increases markedly in brown adipose tissue, continues to decrease in skeletal muscle, nut does not change appreciably in the liver. Because increased incorporation of L-[U-14C]-leucine into brown adipose tissue mitochondrial proteins was observed both in vivo and in vitro, it can be concluded that the mitochondrial protein-synthesizing system of this tissue is directly affected by the acclimation process. The observed changes in mitochondrial protein metabolism of brown adipose tissue and skeletal muscle might be responsible for the development of several morphological and biochemical alterations that characterize the establishment in these tissues of the cold-acclimated state.

Acclimatization↗
PubMed1976

Cellular thermogenesis.

The principal conclusion presented in this review is that no single mechanism underlies any of the examples of basal or altered cellular thermogenesis. Both increased Na+ pump operation and uncoupling may occur to a greater or lesser extent, as may other heat-producing mechanisms. There are areas in which further information is needed in order to explain fully the composite nature of the mechanisms involved in cellular thermogenesis. The control of mitochondrial oxidations in their natural habitat (i.e. inside cells) by regulatory proteins, fatty acids, ions (Ca2+, Na+, K+), cyclic AMP, protein kinases, prostaglandins, purine nucleotides, and other factors must be elucidated. There is evidence for the participation of all of these substances in the control of cellular thermogenesis, but no scheme has been developed that takes them all into account. Further emphasis on the tissue-specific differences in the regulation of mitochondrial function is desirable. The regulation of the biogenesis of mammalian mitochondria is another area currently under intense study for which no clear hypothesis has as yet emerged. Information in this area is needed in order to understand the mechanism and role of mitochondrial adaptations associated with altered thermogenesis in hyperthyroidism, in acclimation to cold, and in exercise training, as well as the nature of altered mitochondrial biogenesis, such as appears to underlie the Luft hypermetabolic syndrome.

Adenosine Triphosphatases↗