Variations in energization parameters and proton conductance induced by cold adaptation and essential fatty acid deficiency in mitochondria of brown adipose tissue in the rat.

Male weanling Long-Evans rats were fed on a low-fat semipurified diet (control diet, 2% sunflower oil; essential fatty acid (EFA) deficient diet, 2% hydrogenated coconut oil) for 9 weeks. In order to modulate need for non-shivering thermogenesis, groups of rats on each diet were exposed at 28 degrees C (thermoneutrality) and at 5 degrees C (cold acclimation) for the last 5 weeks. In brown adipose tissue (BAT) mitochondria, several parameters of mitochondrial energization, protonmotive force (delta p) and its components delta pH and membrane potential, delta psi, were investigated. Simultaneous measurement of oxygen consumption and delta psi (the main component of delta p) was performed by varying alpha-glycerophosphate concentration and the force/flux relationship of the mitochondria was established by comparison of proton conductance, CmH+, over the whole range of protonmotive force. delta p. In the absence of GDP, at 28 degrees C, EFA deficiency induced a marked increase in CmH+. Cold acclimation led to comparable enhanced CmH+ in control and EFA-deficient mitochondria. In the presence of GDP which binds and inhibits the BAT 32 kDa uncoupling protein, CmH+ was the same in 28 degrees C and 5 degrees C control mitochondria, but EFA deficiency led to an enhanced GDP independent CmH+ at 28 degrees C and to a lesser extent at 5 degrees C. These results are discussed with reference to substantial changes in mitochondrial lipid composition induced by the deficiency.

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.

An association between sputum eosinophilia and carcinoma of the lung: a study of 549 patients.

A prospective 11 year study of sputum cytology in 5,475 patients with respiratory diseases other than asthma or Loeffler's syndrome showed that carcinoma of the lung was the commonest single condition associated with a sputum eosinophilia: it occurred in 68 (12.4%) of the 549 patients with pulmonary carcinoma. While clearly not a diagnostic finding, sputum eosinophilia should stimulate, in appropriate cases, a further search for carcinoma. The cause or causes of the eosinophilia are not known at present but the body's reaction to malignancy is a topical subject of study worldwide.

The youngest successful heart transplant in the U.K. A case report.

We report a case of dilated cardiomyopathy in a 7 year-old boy who was assessed and treated medically, but failed to respond. A successful orthotopic cardiac transplantation was performed.

Non-shivering thermogenesis and brown adipose tissue activity in essential fatty acid deficient rats.

The effects of essential fatty acid (EFA) deficiency on energetic metabolism and interscapular brown adipose tissue (BAT) activity were examined in the cold acclimated rat. Weanling male Long-Evans rats were fed on a low fat semipurified diet (control diet, 2% sunflower oil; EFA deficient diet, 2% hydrogenated coconut oil) for 9 weeks. They were exposed at 5 degrees C for the last 5 weeks. In EFA deficient rats, compared to controls, growth retardation reached 22% at sacrifice. Caloric intake being the same in the two groups, it follows that food efficiency was decreased by 40%. Resting metabolism in relation to body surface area was 25% increased. Calorigenic effect of norepinephrine (NE) in vivo (test of non-shivering thermogenesis) underwent a marked decrease of 34%. BAT weight was 21% decreased but total and mitochondrial protein content showed no variation. A 26% increase in purine nucleotide binding per BAT (taken as an index of thermogenic activity) was observed, suggesting that the enhancement in resting metabolism observed was mainly due to increased BAT thermogenesis. However, BAT mitochondria respiratory studies which are more direct functional tests showed a marked impairment of maximal O2 consumption of about 30% with palmitoyl-carnitine or acetyl-carnitine (both in presence of malate) or with alpha-glycerophosphate as substrate. It is likely that this impaired maximal BAT oxidative capacity may explain the impaired NE calorigenic effect in vivo. A possible increase in mitochondrial basal permeability is also discussed.

The influence of acute preoperative pulmonary infarction on the results of heart transplantation.

The presence of acute pulmonary infarction is not uncommon in severely ill patients and is considered by some to be a contraindication to heart transplantation. It has been our policy to accept these patients for operation. The purpose of this investigation is to examine the results of this policy in patients receiving immunosuppression with cyclosporine A and azathioprine. Between September 1982 and April 1985, eight patients undergoing heart transplantation demonstrated clinical and radiographic evidence of acute preoperative pulmonary infarction. These patients represented 5.5% of our heart transplantation population during this period (total = 145). The age range in these eight patients was from 22 to 55 years. Congestive cardiomyopathy was present in four patients, and four patients had ischemic cardiomyopathy. All patients were New York Heart Association functional status class IV. Five of the eight patients were on inotropic support, and one patient had associated renal failure. Pulmonary infarcts were located in the right, middle, or lower lung field in seven patients and in the left lower lung field in one patient. All patients were treated perioperatively by intensive physiotherapy and specific antibiotics. In four patients the lesions resolved on medical treatment alone. Three patients developed extensive empyema and required chest drainage with or without decortication. Two of these patients survived with complete resolution of the lung lesions, and one patient died from prolonged renal failure and sepsis.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of essential fatty acid deficiency on brown adipose tissue activity in rats maintained at thermal neutrality.

1. The consequences of essential fatty acid (EFA) deficiency on the resting metabolism, food efficiency and brown adipose tissue (BAT) thermogenic activity were examined in rats maintained at thermal neutrality (28 C). 2. Weanling male Long-Evans rats were fed a hypolipidic semi-purified diet (control diet: 2% sunflower oil; EFA-deficient diet: 2% hydrogenated coconut oil) for 9 weeks. 3. They were kept at 28 C for the last 5 weeks. Compared to controls, in EFA-deficient rats the growth shortfall reached 21% at killing. 4. As food intake was the same in EFA-deficient and control rats, food efficiency was thus decreased by 40%. 5. Resting metabolism expressed per surface unit was 15% increased. 6. Non-renal water loss was increased by 88%. 7. BAT weight was 28% decreased but total and mitochondrial proteins were not modified. 8. Heat production capacity, tested by GDP binding per BAT was 69% increased in BAT of deficient rats. 9. The stimulation of BAT was established by two other tests: GDP inhibition of mitochondrial O2 consumption and swelling of mitochondria. 10. It is suggested that the observed enhancement of resting metabolism in EFA-deficient rats is, in part, due to an activation of heat production in BAT.