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Innervation of mammalian white adipose tissue: implications for the regulation of total body fat.

We review the extensive physiological and neuroanatomical evidence for the innervation of white adipose tissue (WAT) by the sympathetic nervous system (SNS) as well as what is known about the sensory innervation of this tissue. The SNS innervation of WAT appears to be a part of the general SNS outflow from the central nervous system, consisting of structures and connections throughout the neural axis. The innervation of WAT by the SNS could play a role in the regulation of total body fat in general, most likely plays an important role in regional differences in lipid mobilization specifically, and may have a trophic affect on WAT. The exact nature of the SNS innervation of WAT is not known but it may involve contact with adipocytes and/or their associated vasculature. We hypothesize that the SNS innervation of WAT is an important contributor to the apparent "regulation" of total body fat.

Adipose Tissue↗

Activation of antilipolytic alpha(2)-adrenergic receptors by epinephrine during exercise in human adipose tissue.

The involvement of the antilipolytic alpha(2)-adrenergic pathway and the specific role of epinephrine in the control of lipolysis during exercise in adipose tissue (AT) were investigated in healthy male subjects (age: 24.1 +/- 2.2 yr; body mass index: 23.0 +/- 1.6). An in vitro study carried out on isolated adipocytes showed that the weak lipolytic effect of epinephrine was potentiated after blockade of alpha(2)-adrenergic receptor (AR) by an alpha(2)-AR antagonist and reached that of isoproterenol, a beta-AR agonist. The effect of the nonselective alpha(2)-AR antagonist phentolamine on the response of the extracellular glycerol concentration (EGC) in AT during two successive bouts of aerobic exercise (50% maximum O(2) uptake, 60 min duration) was evaluated using the microdialysis method. The metabolic responses measured in perfused probes with Ringer solution were compared with those obtained in perfused probes with Ringer plus 0.1 mmol/l phentolamine. Plasma norepinephrine level was not different during the two exercise bouts, whereas that of epinephrine was 2.5-fold higher during the second exercise. EGC in AT was twofold higher in the second compared with the first exercise, and the same response pattern was found for plasma glycerol. The exercise-induced increase in EGC was higher in the probe perfused with phentolamine compared with the control probe in both bouts of exercise. However, the potentiating effect of phentolamine on EGC was significant during the second exercise bout but did not reach a significant level during the first. These results suggest that epinephrine is involved in the control of lipid mobilization through activation of antilipolytic alpha(2)-AR in human subcutaneous AT during exercise.

Adipocytes↗

A single bout of exercise induces beta-adrenergic desensitization in human adipose tissue.

This study was designed to assess whether physiological activation of the sympathetic nervous system induced by exercise changes adipose tissue responsiveness to catecholamines in humans. Lipid mobilization in abdominal subcutaneous adipose tissue was studied with the use of a microdialysis method in 11 nontrained men (age: 22. 3 +/- 1.5 yr; body mass index: 23.0 +/- 1.6). Adipose tissue adrenergic sensitivity was explored with norepinephrine, dobutamine (beta(1)-agonist), or terbutaline (beta(2)-agonist) perfused during 30 min through probes before and after 60-min exercise (50% of the maximal aerobic power). The increase in extracellular glycerol concentration during infusion was significantly lower after the exercise when compared with the increase observed before the exercise (P < 0.05, P < 0.02, and P < 0.01, respectively, for norepinephrine, dobutamine, and terbutaline). In a control experiment realized without exercise, no difference in norepinephrine-induced glycerol increase between the two infusions was observed. To assess the involvement of catecholamines in the blunted beta-adrenergic-induced lipolytic response after exercise, adipose tissue adrenergic sensitivity was explored with two 60-min infusions of norepinephrine or epinephrine separated by a 60-min interval. With both catecholamines, the increase in glycerol was significantly lower during the second infusion (P < 0.05). The findings suggest that aerobic exercise, which increased adrenergic activity, induces a desensitization in beta(1)- and beta(2)-adrenergic lipolytic pathways in human subcutaneous adipose tissue.

Adipose Tissue↗

Photoperiodic regulation of gene expression in brown and white adipose tissue of Siberian hamsters (Phodopus sungorus).

Siberian hamsters exhibit seasonal fluctuations in white adipose tissue (WAT) mass, with peaks in long "summerlike" days (LDs) and nadirs in short "winterlike" days (SDs). These responses can be mimicked in the laboratory after transfer from LDs to SDs. The purpose of the present study was to test whether changes in WAT and brown adipose tissue (BAT) gene expression that are mediated by the sympathetic nervous system in other obesity models are also associated with seasonal adiposity changes in Siberian hamsters. SDs decreased WAT mass and leptin mRNA, increased WAT beta(3)-adrenoceptor mRNA, and induced retroperitoneal WAT uncoupling protein-1 mRNA (the latter measured by RT-PCR, others measured by ribonuclease protection assay) while increasing BAT uncoupling protein-1 and peroxisome proliferator-activated receptor-gamma coactivator-1 mRNAs. These effects were not due to SD-induced gonadal regression and largely occurred before the usual SD-induced decreases in food intake. Thus the SD-induced decreased adiposity of Siberian hamsters may be due to a coordinated suite of WAT and BAT gene transcription changes ultimately increasing lipid mobilization and utilization.

Adipose Tissue, Brown↗

Metabolic adrenergic changes during submaximal exercise and in the recovery period in man.

The urinary excretion of dihydroxyphenylalanine (DOPA), catecholamines (CA) [dopamine (DA), norepinephrine (NE), and epinephrine (e)], their 3-O-methylated derivatives [3-O-methyldopamine (3-MT), normetanephrine (NMN), and metanephrine (MN)], and their deaminated metabolites [dihydroxyphenylacetic acid (DOPAC) and vanilmandelic acid (VMA)] was studied in six healthy men, at rest during short-term (15 min) or exhaustive submaximal exercise, and in the 2-h postexercise recovery period. During short-term exercise only NE and VMA excretions increased, whereas in postexercise period only DA output was enhanced. Exhaustive muscular work induced a rise in NE and E excretion during the test, and an increase in DA, NE, and NMN urinary levels during postexercise recovery, while the output of deaminated metabolites was unaltered. It is concluded that both release and synthesis of CA are stimulated by submaximal exercise, which induces, in addition to NE, a specific release of DA. A possible role of NE in lipid mobilization during recovery from exhaustive muscular work is evoked. The origin and role of released DA are also discussed.

3,4-Dihydroxyphenylacetic Acid↗

Substrates for cold thermogenesis in thyrotoxic dogs.

The influence of thyrotoxicosis on energy supply during cold exposure was studied in normal and chronically thyroxine (T4)-treated normothermic dogs exposed to neutral (Ta,N = +25 degrees C) or cold (Ta,C = -21 degrees C) ambient temperatures. At Ta,N, T4 treatment significantly increased VO2, glucose turnover, and plasma 3-hydroxybutyrate concentration. The percentage of glucose turnover derived from alanine also increased in spite of lower alanine release. In cold, T4 treatment did not significantly modify O2 consumption, glucose turnover, or plasma alanine concentration, but plasma hydroxybutyrate, alanine clearance, and alanine conversion into glucose were significantly increased compared with control. It is suggested that in cold the main effect of thyrotoxicosis on energy supply, in addition to a trend toward lipid mobilization, is an increase in hepatic alanine extraction and conversion into glucose in the presence of lower muscular alanine delivery.

3-Hydroxybutyric Acid↗

Lipolytic response of fat cells to catecholamines in sedentary and exercise-trained women.

It has been shown that adipose tissue lipolytic activity is increased in endurance-trained subjects. In women, adipose tissue is extensive and it was thought interesting to confirm that endurance training increases the capacity of female adipose tissue to mobilize lipids, and moreover to more fully understand the mechanisms involved. So, biopsies of fat were obtained from the periumbilical region of 13 trained female runners (T) and 17 sedentary women (S) and the in vitro response to catecholamines of the collagenase-isolated fat cells was studied. Glycerol release, chosen as adipocyte lipolysis indicator, was measured by bioluminescence for various epinephrine and norepinephrine concentrations. In both groups, these substances provoked an increase in lipolysis, but the response was significantly higher in T. In both groups, isoproterenol increased the lipolytic activity above basal concentrations at 10(-8) M and above. Lipolytic activity in T was significantly higher (P less than 0.01) than the S control at 10(-7) M and above. Epinephrine plus propranolol decreased lipolysis in both groups, but at 10(-5) M, lipolytic activity was significantly lower in S than in T (P less than 0.05). It is concluded that in female subjects, endurance training increases the sensitivity of subcutaneous abdominal adipose tissue to the lipolytic action of catecholamines; this effect seems to be related both to a decreased efficiency of the alpha 2-adrenergic pathway and to an increased efficiency of the beta-adrenergic pathway. This latter effect seems to take place at a step beyond the receptor-adenylate cyclase system in the lipolytic cascade.

Adipose Tissue↗

Adipose tissue lipolysis is increased during a repeated bout of aerobic exercise.

The goal of the study was to examine whether lipid mobilization from adipose tissue undergoes changes during repeated bouts of prolonged aerobic exercise. Microdialysis of the subcutaneous adipose tissue was used for the assessment of lipolysis; glycerol concentration was measured in the dialysate leaving the adipose tissue. Seven male subjects performed two repeated bouts of 60-min exercise at 50% of their maximal aerobic power, separated by a 60-min recovery period. The exercise-induced increases in extracellular glycerol concentrations in adipose tissue and in plasma glycerol concentrations were significantly higher during the second exercise bout compared with the first (P < 0.05). The responses of plasma nonesterified fatty acids and plasma epinephrine were higher during the second exercise bout, whereas the response of norepinephrine was unchanged and that of growth hormone lower. Plasma insulin levels were lower during the second exercise bout. The results suggest that adipose tissue lipolysis during aerobic exercise of moderate intensity is enhanced when an exercise bout is preceded by exercise of the same intensity and duration performed 1 h before. This response pattern is associated with an increase in the exercise-induced rise of epinephrine and with lower plasma insulin values during the repeated exercise bout.

Adipose Tissue↗

Flight effects on plasma levels of neurohypophysial hormones in homing pigeons.

A significant increase in the circulating levels of arginine vasotocin (AVT), without change in plasma osmolality, was observed in homing pigeons immediately after a flight of 48 km, lasting 60-80 min. This increase in plasma AVT is perceived as part of an overall homeostatic mechanism of mobilizing lipid as fuel for the flight muscles, of water conservation and temperature regulation in the body during the homing flight within the specific distance and duration of flight and under normal weather conditions. However, there was no change in plasma levels of mesotocin (MT) which suggests that the birds were under no significant stress during the flight.

Animals↗

Effect of methylxanthines on lactational performance of rats.

Caffeine, theophylline and theobromine are commonly consumed methylxanthines. There are conflicting reports that methylxanthines may adversely affect the outcome of pregnancy. The effects of methylxanthines on lactational performance were investigated by administration of pure alkaloids via drinking water to Wistar albino rats throughout pregnancy and lactation. Litter growth was used as an index of lactational performance in relation to maternal food and fluid intake, changes in weight, and lipid content of the carcass. Caffeine induced increased fluid intake (p less than 0.01). While theophylline produced no significant differences in litter growth, maternal weight and carcass fat during pregnancy/lactation compared with controls, caffeine and theobromine significantly enhanced litter growth (p less than 0.05 and 0.01, respectively). The enhancement in pup growth did not involve increases in maternal food intake or maternal lipid mobilization.

Animals↗

Different acute in vivo effects of bacterial derived and pituitary growth hormone preparations on plasma levels of glucagon, insulin and free fatty acids in rabbits.

Intravenous injection of high doses of bacterial derived growth hormone (1 and 2 mg Somatonorm) did not affect the plasma levels of glucagon, insulin and free fatty acids in fasted and fed rabbits. On the other hand, 1 and 2 mg human extracted growth hormone (Crescormon) had stimulatory effects on plasma levels of glucagon, insulin and free fatty acids. These results indicate that the observed stimulatory effects in the rabbits were not due to the growth hormone molecule itself. It was shown by gel filtration and SDS electrophoresis that Crescormon contained constituents that were not present in Somatonorm. The differences in the observed metabolic effects of bacterial derived and pituitary growth hormone preparations in the rabbits could possibly be attributed to a human pituitary lipid-mobilizing factor LMF.

Animals↗

Gram-negative bacteria sepsis in the rat and tissue lipolytic activity on LCT and MCT/LCT-based commercial parenteral emulsions.

The aim of this study was to evaluate the effect of a gram-negative bacteria sepsis on the activity of the enzymes lipoprotein lipase (LPL) and hepatic lipase (HL), involved in the clearance of circulating triacylglycerol-rich fat particles. Fasting rats were intravenously injected with NaCl9 g.l-1, live or heat-killed Pseudomonas aeruginosa bacteria. After 18 h the animals were killed. When compared to controls, the 2 treated groups showed an increase in body temperature, cholesterolemia, triglyceridemia and a decrease in ketonemia, proteinemia, albuminemia and in the in vitro activity of diaphragm, heart and adipose tissue LPL and of HL. The decrease in the enzyme activities occurred independent of the type of emulsion used as in vitro substrate, whether it was based on long-chain triglycerides or on medium- and long-chain triglycerides, but in any case the activity was lower with the first than with the second type of fat emulsion.

Animals↗

13C-NMR spectroscopy of human atherosclerotic lesions. Relation between fatty acid saturation, cholesteryl ester content, and luminal obstruction.

Previous investigations have used 13C-nuclear magnetic resonance (NMR) spectroscopy to demonstrate the similarities between lipoproteins and the mobile lipids of atheroma. In this study, we tested the hypothesis that 13C-NMR changes are related to indices of histological severity. We classified 20 human arteries according to their obstruction ratio (OR), defined as the ratio of the plaque area to the area delimited by the external elastic lamina. In group A, OR was < 40%, and in group B, OR was > 40%. We analyzed at 9.4 T the resonances of unsaturated (UFA) and polyunsaturated (PUFA) carbons, the resonances of the carbons 19 and 21 (C19, C21) of cholesteryl esters (CE), the methine carbon peak of fatty acids (CH2)n, the choline peak from phospholipids (PL), and the glycerol peak from triglyceride (TG). The UFA/PUFA, UFA/(CH2)n, and PUFA/(CH2)n ratios are markers of fatty acid saturation. (C19, C21)/(CH2)n, choline/(CH2)n, and glycerol/(CH2)n are indices of CE, PL, and TG content, respectively. UFA/PUFA in group A is 1.15 +/- 0.34 versus 1.63 +/- 0.32 in group B (P = .005). PUFA/(CH2)n is 0.26 +/- 0.10 in group A versus 0.16 +/- 0.04 in group B (P = .049). C19, C21/(CH2)n in group A is 0.32 +/- 0.15 versus 0.63 +/- 0.23 for group B (P = .003). No significant difference was found in UFA/(CH2)n or in the TG or PL ratios. 13C spectral examination of human atherosclerosis demonstrates decreased resonances for polyunsaturated fatty acyl chains and cholesteryl esters with increasing obstruction.

Adult↗