The lipid composition of plasma membrane and mitochondrial fractions from epididymal adipocytes of cold-acclimated rats.

1. The effects of cold acclimation (5 degrees C) on the lipid composition of plasma membrane and mitochondrial fractions from epididymal adipocytes of rats were studied. 2. The adipocyte plasma membrane fraction of the cold-acclimated rats had lower lipid, phospholipid and cholesterol to protein weight ratios, a lower cholesterol to sphingomyelin molar ratio, and a higher linoleic acid content in the phospholipids than controls. 3. The mitochondrial fraction of the cold-acclimated rat adipocyte had lower ratios of cholesterol to protein (weight), to phospholipid and to cardiolipin (molar), and less sphingomyelin content than did controls. 4. These data, discussed in terms of alterations in physical and biochemical properties, indicate cold-induced changes at the membrane level in rat epididymal adipocytes.

Relation between membrane phospholipid composition, fluidity and function in mitochondria of rat brown adipose tissue. Effect of thermal adaptation and essential fatty acid deficiency.

Male weanling rats were maintained either at 28 degrees C (thermoneutrality) or at 5 degrees C (cold adaptation). During 9 weeks they were fed either a 2% hydrogenated coconut oil diet deficient in essential fatty acids or a diet containing 2% sunflower oil. The respective incidences of cold adaptation and of EFA deficiency on lipid composition of mitochondrial membranes from brown adipose tissue (BAT) were investigated. Using 1,6 diphenylhexatriene (DPH) as a probe, the parameters of membrane fluidity were estimated by steady-state fluorescence polarization measurements (rs) and by time-resolved fluorescence anisotropy decay (order parameter S). Cold acclimation induced a decrease of phosphatidylcholine to phosphatidylethanolamine (PC/PE ratio), an increase of the total fatty acid unsaturation index (T.U.). EFA deficiency had the same effect as cold on the PC/PE ratio, but decreased T.U. Cold adaptation induced a larger decrease of S than of rs, whereas EFA deficiency only increased rs and did not modify S. In liposomes prepared from mitochondrial lipids, rs values were smaller than in whole mitochondria. Both in cold-adapted and in EFA-deficient rats the variations of rs were correlated with lipid unsaturation. Comparison between BAT thermogenic activity, assessed by GDP binding and proportions of PE and PC showed a high correlation suggesting a change in the membrane occurring with the increase of mitochondrial activity that could be related to phospholipid composition rather than to membrane fluidity.

Effect of sympathetic de-activation on thermogenic function and membrane lipid composition in mitochondria of brown adipose tissue.

Male Long-Evans rats (9 weeks of age) were exposed to cold (5 degrees C) for 10 days. Then, sympathetic de-activation of brown adipose tissue (BAT) was performed either by BAT surgical denervation (Sy) or by warm re-exposure at 28 degrees C (WE) for 4 days. The incidence of the two treatments on thermogenic activity of BAT mitochondrial membranes and their lipid composition was investigated. Sy and WE induced a large decrease in GDP binding on the uncoupling protein (UCP) (43% and 82%, respectively). Several parameters of mitochondrial energization were investigated. Sy and WE substantially decreased UCP-dependent proton conductance (CmH+) over the whole range of protonmotive force. CmH+ showed greater variation than GDP binding. The low basal UCP-independent CmH+ was the same in all groups. Comparison of GDP binding and CmH+ with UCP content which is not modified revealed a masking of both the nucleotide binding site and the proton channel. Sy and WE induced the same increase of phosphatidylcholine to phosphatidylethanolamine ratio (16%) but had opposite effects on fatty acid unsaturation. The results were discussed with reference to functional significance of these variations in BAT mitochondrial thermogenic activity and lipid composition.

Beta-adrenergic receptors in white fat cells of cold-acclimated rats.

Beta-adrenergic receptors were studied in membranes prepared from isolated fat cells obtained from both control and cold-acclimated rats. Beta-adrenergic receptors were identified using beta-adrenergic antagonist, (-) - [3H] dihydroalprenolol. Scatchard plots of specific binding suggest the existence of two binding sites for (-) - [3H] dihydroalprenolol with different affinities. Beta-adrenergic agonists competed for specific binding sites with typical beta 1-adrenergic specificity. There appears to be approximately 5,000 sites of high affinity per fat cell. Cold-acclimation (4 weeks at 4 degrees C) reduced adipocyte size; it did not appear to alter either the maximal number of binding sites of high and low affinity, or their affinity for beta-antagonists or agonists; however the density of binding sites in the fat cell was increased in cold-acclimated rats. It is concluded that the cold-adaptative process which induces in vivo the enhancement of calorigenic effect of norepinephrine is not found at the level of beta-receptors in white fat cells. The increased lipolytic response to norepinephrine observed in vitro in epididymal fat may be explained by cold-induced modifications in cell size and number.

Glycerokinase activity in brown and white adipose tissues of cold-adapted obese Zucker rats.

Glycerokinase activity was measured in the brown and white adipose tissues compared with that in the liver obese Zucker rats adapted or not adapted to cold. In white adipose tissue total activity was low but higher in the fa/fa rats than in the Fa/ones; cold adaptation did not modify this activity. In brown adipose tissue specific activity was higher than in white; specific activity was twice as high in the fa/fa rats than in the Fa/-. Cold-adaptation induced an increase in the activity in the Fa rats and a decrease in the fa/fa rats. The results are discussed with regard to the cold-induced increase in the energetic efficiency of the tissue.

Characteristics of beta-adrenergic receptors in isolated cells and in crude membranes of brown adipose tissue.

In relation to decreased metabolic sensitivity to catecholamines observed, in vitro, in brown fat of cold-acclimated rats, beta-adrenergic receptors were studied in isolated cells and in a crude membrane preparation from rat interscapular brown adipose tissue. [3H] dihydroalprenolol binding had the same characteristics in both types of preparation; competition studies of [3H] dihydroalprenolol binding led to the characterization of beta 1 subtype adrenergic receptors with a lower affinity of beta-adrenergic agonists for [3H] dihydroalprenolol binding sites in membranes than that found in isolated cells. Cold acclimation produced, in isolated cells only, a decrease of 41% in the [3H] dihydroalprenolol binding sites and a beta-adrenergic agonist affinity increase. It is concluded that beta-adrenergic receptor decrease could be a factor, at the hormone receptor interaction level, in the regulation of the transmission of biological action responsible for the cold-induced decrease in catecholamine responsiveness in brown adipose tissue. For a study of the desensitization process in brown fat, isolated cells seem to offer certain advantages over a crude membrane preparation.

Prostaglandins E2 and F alpha levels in white and brown adipose tissues of cold acclimated rats as measured by a new micromethod.

A new micro-method was used to determine the effects of cold acclimation of rats on the levels of prostaglandin E2 and F alpha in both white and brown adipose tissues. Whereas PGF alpha levels were significantly higher than PGE2 levels in white fat, no difference between the amounts of the two prostaglandins was observed in brown fat. In both tissues, cold acclimation did not induce any change in prostaglandin levels.

Evidence for a cold-induced aldosterone stimulation in the rat.

This study was undertaken to determine the secretion of aldosterone by male Long-Evans rats acclimated for six weeks to moderate cold (15 C), in comparison with rats maintained at thermo-neutral temperature (28 C). The following determinations were made: corticosteroids in plasma and adrenals, PRA, and hydromineral balance. Cold acclimation highly increased the plasma and adrenal levels of aldosterone and corticosterone. The cold stimulation of aldosterone was induced neither by the renin-angiotensin system, nor by alterations of hydromineral balance: PRA, plasma sodium and potassium concentrations, blood hematocrit, and hydromineral balance at 15 C and 28 C did not differ. Moreover this stimulation was induced neither by ACTH, nor by any other hypophyseal factors, since plasma aldosterone levels remained high in hypophysectomized rats. This study provides evidence of an aldosterone stimulation which appeared during moderate cold acclimation; the origin of this stimulation must be investigated.

Effects of the rearing temperature on the temporal feeding pattern of the staggerer mutant mouse.

The temporal feeding pattern of the staggerer mutant mouse was tested under two thermal rearing conditions, 28 degrees C and 22 degrees C, and compared to that of the normal mouse. At a temperature of 28 degrees C, the mutants were observed to eat more than the normal mice did although they showed a drastic body weight deficit. At 22 degrees C, this peculiarity was still observed, but with an altered feeding pattern, wherein the mutants ate as much during both the dark and light phases.

Effects of cold acclimation on the energetic metabolism of the staggerer mutant mouse.

Staggerer mutant mice are lean despite their hyperphagia. Brown adipose tissue activity may be implicated in this phenomenon. The aim of this work is to determine the energetic metabolism and to detail some characteristics of the brown adipose tissue of Staggerer mutant mice born and reared either at 28 degrees C (within the thermoneutral zone) or 22 degrees C (cold temperature) compared to nonmutant control mice. In mutant mice reared at thermoneutrality the resting metabolism was found to be higher than that of controls, and further the activity of the brown adipose tissue increased as indicated in relative mass, composition and cytochrome oxydase activity. A stimulatory effect of cold exposure was observed in both mutant and nonmutant mice. It is suggested that Staggerer mice may provide a good model for the study of the cold-induced or diet-induced mechanisms of brown fat stimulation.

Spatial navigation of staggerer and normal mice during juvenile and adult stages.

Staggerer mutant mice were compared to normal mice of two different ages (2-6 mo) in two tasks requiring navigational skills in a circular maze visible platform condition and a T-maze. Staggerer mutants had higher latencies than normal mice in both tests. The performance of normal mice worsened with age for both tests. The aging factor interacted with the genotype factor only in the circular maze, where the mutant-nonmutant differential was wider among juvenile animals. In neither task was there evidence of a more pronounced impairment with aging in staggerer mutants. It remains to be determined in this mutant at more advanced stages of aging or in other models of chronic neural disease whether early neuropathology accelerates brain aging.

In vivo effects of indomethacin and cyclophosphamide on CFU-GM proliferation and cyclic nucleotide levels in bone marrow of mice.

The effects of indomethacin (6 mg/kg daily, orally, for 4 days) or cyclophosphamide (150 mg/kg, a single dose, intraperitoneally) on myelopoiesis were studied in mice. A hyperplasia of the committed stem cell compartment (rise in the recognizable myeloid precursors, increase of both colony forming capacity and number of CFU-GM in S-phase) associated to an increase of cyclic AMP and GMP amounts in bone marrow cells of treated mice were observed. These results suggest a possible relationship between the in vitro enhancement of proliferative activity of CFU-GM and the in vivo increase of both cyclic nucleotide levels in medullary environment.

Effects of fasting and refeeding on energetic metabolism of cold acclimated rats.

In rats acclimated at 5 degrees C or 28 degrees C (thermal neutrality), overnight fasting induced decreases in body and brown adipose tissue (BAT) weights and led to a larger decrease in resting metabolism (RM) in the 5 degrees C rats than in the 28 degrees C group. Refeeding significantly enhanced RM (diet-induced thermogenesis) in a greater extent in 5 degrees C than in 28 degrees C rats. This effect was inhibited by propranolol (beta adrenergic receptor antagonist) in 28 degrees C but was only halved in 5 degrees C rats. The capacity for nonshivering thermogenesis as determined by norepinephrine infusion was reduced by fasting only in 28 degrees C group; it remained unchanged in cold acclimated rats despite the large lipid utilization induced by fasting.

[Malignant degeneration in testicular feminization. Apropos of a case]. / Dégénérescence maligne du testicule féminisant. A propos d'un cas.

The authors describe the main therapeutic features found in a case of testicular feminisation that became malignant. Bilateral gonadal ablation should be carried out after puberty for fear of malignancy. When cancer occurs treatment is best decided on the grounds of extension to the lymph nodes and the histological findings in the tumour. Where there is no extension to the lymph nodes, surgery should be carried out on the gonads with radiotherapy to the lymph nodes. If the tumour is not clearly a seminoma the lymph nodes should be removed before radiotherapy is started.

[Functional exploration of brown adipose tissue using beta3 agonists]. / Exploration fonctionnelle du tissu adipeux brun par les beta 3 agonistes.

In view to utilize beta 3 adrenoceptor agonists for the investigation of body lipid metabolism, a study of the effects of BRL 37344 on the functional activity of the brown adipose tissue was performed in the Rat. It is known that this tissue is the principal site of heat production for nonshivering thermogenesis mainly due to the oxidation of fatty acids under the control of norepinephrine (NA) released from the sympathetic nervous system. In order to stimulate the activity of the tissue, rats were reared at 16 degrees C. When they were one month old, they were divided in two groups; one group received a surgical sympathectomy of the interscapular brown adipose tissue (TABI) (S group); the other group was sham-operated (T group). The resting metabolism was estimated by the continuous measurement of O2 consumption and CO2 release, at an ambient temperature of 25 degrees C. The animal capacity for nonshivering thermogenesis was determined by increased O2 consumption following i.p. administration of NA or BRL 37344. In the S group a large decrease in TABI NA content and a decrease in resting metabolism were observed. In both groups VO2 was increased by the two drugs; the increase was linearly related to the dose of BRL (between 2.5 to 10 micrograms/kg); but it was 3 times as high in the T group as in the S group. Moreover, the effect of BRL was 40 fold greater than the effect of NA. These results seem to indicate that, in cold reared rats, a part of nonshivering thermogenesis may be mediated by the beta 3 receptors of the brown fat. It may be concluded that the rats born in cold conditions are good models to study the role of beta 3 receptors in the energetic activity of this tissue very profuse in infant but not in adult man.

[Shoulder movements after mammectomy with conservation of muscle. Report of 100 cases]. / Etude de la motricité de l'épaule après mammectomie conservatrice de la musculature. A propos de 100 observations.

One hundred patients were treated by a Patey type conservative radical mammectomy with or without associated radiotherapy. Objective numerically rated comparison of the frequency and degree of limitation of the different shoulder movements after surgical treatment alone showed that abduction was the movement most markedly and frequently limited. This was followed, in decreasing order of frequency and degree, by limitation of amplitude, anterior flexion, external rotation, posterior flexion, and internal rotation. In cases with associated radiotherapy, highest percentages of maximal imitation for each movement occurred in those undergoing pre-operative cobalt therapy, and particularly involved abduction, posterior flexion, and external rotation. Patey type mammectomy provides improved functional results when compared with the classical Halsted's operation, but its technique has still to be perfected, a useful basis for this being a detailed analysis of its possible sequelae.