Lipoprotein-lipase activity of human skeletal-muscle and adipose tissue after intensive physical exercise

Seven young, healthy subjects performed bicycle exercise with a working load leading to exhaustion after one hour of work. The tests were done in the afternoon in the fed state. The serum insulin concentrations decreased from 22 to 4 mU/1 and plasma glucagon increased from 241 to 340 pg/1 already after 30 min of work. The level of adipose tissue lipoprotein lipase activity (LPLA) did not fall as had been expected, but increased. The skeletal muscle LPLA was unchanged. The results indicate that during the first hour of heavy exercise the heparin-releasable LPLA in tissues is not influenced by the work induced changes in serum hormone levels.     

Lipoprotein-lipase activity of human skeletal-muscle and adipose tissue after intensive physical exercise.

Seven young, healthy subjects performed bicycle exercise with a working load leading to exhaustion after one hour of work. The tests were done in the afternoon in the fed state. The serum insulin concentrations decreased from 22 to 4 mU/l and plasma glucagon increased from 241 to 340 pg/l already after 30 min of work. The level of adipose tissue lipoprotein lipase activity (LPLA) did not fall as had been expected, but increased. The skeletal muscle LPLA was unchanged. The results indicate that during the first hour of heavy exercise the heparin-releasable LPLA in tissues is not influenced by the work induced changes in serum hormone levels.     

New concepts in white adipose tissue physiology

Numerous studies address the physiology of adipose tissue (AT). The interest surrounding the physiology of AT is primarily the result of the epidemic outburst of obesity in various contemporary societies. Briefly, the two primary metabolic activities of white AT include lipogenesis and lipolysis. Throughout the last two decades, a new model of AT physiology has emerged. Although AT was considered to be primarily an abundant energy source, it is currently considered to be a prolific producer of biologically active substances, and, consequently, is now recognized as an endocrine organ. In addition to leptin, other biologically active substances secreted by AT, generally classified as cytokines, include adiponectin, interleukin-6, tumor necrosis factor-alpha, resistin, vaspin, visfatin, and many others now collectively referred to as adipokines. The secretion of such biologically active substances by AT indicates its importance as a metabolic regulator. Cell turnover of AT has also recently been investigated in terms of its biological role in adipogenesis. Consequently, the objective of this review is to provide a comprehensive critical review of the current literature concerning the metabolic (lipolysis, lipogenesis) and endocrine actions of AT.     

Physical activity ameliorates the function of organs via adipose tissue in metabolic diseases

Adipose tissue is a dynamic organ in the endocrine system that can connect organs by secreting molecules and bioactive. Hence, adipose tissue really plays a pivotal role in regulating metabolism, inflammation, energy homeostasis, and thermogenesis. Disruption of hub bioactive molecules secretion such as adipokines leads to dysregulate metabolic communication between adipose tissue and other organs in non-communicable disorders. Moreover, a sedentary lifestyle may be a risk factor for adipose tissue function. Physical inactivity leads to fat tissue accumulation and promotes obesity, Type 2 diabetes, cardiovascular disease, neurodegenerative disease, fatty liver, osteoporosis, and inflammatory bowel disease. On the other hand, physical activity may ameliorate and protect the body against metabolic disorders, triggering thermogenesis, metabolism, mitochondrial biogenesis, β-oxidation, and glucose uptake. Furthermore, physical activity provides an inter-organ association and cross-talk between different tissues by improving adipose tissue function, reprogramming gene expression, modulating molecules and bioactive factors. Also, physical activity decreases chronic inflammation, oxidative stress and improves metabolic features in adipose tissue. The current review focuses on the beneficial effect of physical activity on the cardiovascular, locomotor, digestive, and nervous systems. In addition, we visualize protein-protein interactions networks between hub proteins involved in dysregulating metabolic induced by adipose tissue.     

Glucocorticoids and regulation of phosphoenolpyruvate carboxykinase activity in rat brown adipose tissue.

Studied were performed to examine the factors that might regulate phosphoenolpyruvate carboxykinase (PEPCK) activity in rat brown adipose tissue (BAT) and to determine the role played by glucocorticoids in regulating this enzyme. Comparison was made to white adipose tissue (WAT) where PEPCK activity is known to be glucocorticoid regulated. PEPCK activity in BAT did not respond to adrenalectomy or dexamethasone, whereas WAT activity was increased and decreased, respectively, by these maneuvers. Three conditions were found in which BAT PEPCK activity was stimulated: 1) fasting, 2) feeding a high-fat/low-carbohydrate diet, and 3) during the neonatal period. In each case glucocorticoid treatment prevented the stimulation in PEPCK activity and restored the enzyme to base-line levels. In conditions 1 and 2, enzyme activity was also stimulated in WAT, but in contradistinction to BAT, glucocorticoid administration reduced activity to low levels significantly below base-line activity. Two conditions were found which suppressed PEPCK activity in BAT: exposure to a cold environment and feeding a high-protein/low-fat diet. WAT PEPCK was unaltered by exposure to cold. Thus, differences in PEPCK regulation between BAT and WAT were demonstrated, and the response to glucocorticoids was unique in BAT.     

Interstitial glycerol concentrations in human skeletal muscle and adipose tissue during graded exercise

AIM: It is not clear how lipolysis changes in skeletal muscle and adipose tissue during exercise of different intensities. We aimed at estimating this by microdialysis and muscle biopsy techniques. METHODS: Nine healthy, young men were kicking with both legs at 25% of maximal power (Wmax) for 45 min and then simultaneously with one leg at 65% and the other leg at 85% Wmax for 35 min. RESULTS: Glycerol concentrations in skeletal muscle and adipose tissue interstitial fluid and in arterial plasma increased (P<0.001) during low intensity exercise and increased (P<0.05) even more during moderate intensity exercise. The difference between interstitial muscle and arterial plasma water glycerol concentration, which indicates the direction of the glycerol flux, was positive (P<0.05) at rest (21 +/- 9 microM) and during exercise at 25% Wmax (18 +/- 6 microM). The difference decreased (P<0.05) with increasing exercise intensity and was not significantly different from zero during exercise at 65% (-11 +/- 17 microM) and 85% (-12 +/- 13 microM) Wmax. In adipose tissue, the difference between interstitial and arterial plasma water glycerol increased (P<0.001) with increasing intensity. The net triacylglycerol breakdown, measured chemically from the biopsy, did not differ significantly from zero at any exercise intensity although directional changes were similar to microdialysis changes. CONCLUSIONS: Skeletal muscle releases glycerol at rest and at low exercise intensity but not at higher intensities. This can be interpreted as skeletal muscle lipolysis peaking at low exercise intensities but could also indicate that glycerol is taken up in skeletal muscle at a rate which is increasing with exercise intensity.     

Expression and regulation of osteoprotegerin in adipose tissue

PURPOSE: Osteoprotegerin (OPG), a potent inhibitor of osteoclastic bone resorption, has a variety of biological functions that include anti-inflammatory effects. Adipocytes and osteoblasts share a common origin, and the formation of new blood vessels often precedes adipogenesis in developing adipose tissue microvasculature. We examined whether OPG is secreted from adipocytes, therefore contributing to the prevention of neovascularization and protecting the vessels from intimal inflammation and medial calcification. MATERIALS AND METHODS: The mRNA expression of OPG and receptor activator of NF-kappaB ligand (RANKL) was measured in differentiated 3T3L1 adipocytes and adipose tissues. RESULTS: OPG mRNA expression increased with the differentiation of 3T3L1 adipocytes, while RANKL expression was not significantly altered. OPG mRNA was expressed at higher levels in white adipose tissue than in brown adipose tissue and was most abundant in the epididymal portion. In differentiated 3T3L1 adipocytes, Rosiglitazone and insulin reduced the OPG/RANKL expression ratio in a dose- and time- dependent manner. In contrast, tumor necrosis factor-alpha (TNF-alpha) increased the expression of both OPG and RANKL in a time-dependent manner. The OPG/RANKL ratio was at a maximum two hours after TNF-alpha treatment and then returned to control levels. Furthermore, OPG was abundantly secreted into the media after transfection of OPG cDNA with Phi C31 integrase into 3T3L1 cells. CONCLUSION: Our results indicate that OPG mRNA is expressed and regulated in the adipose tissue. Considering the role of OPG in obesity-associated inflammatory changes in adipose tissue and vessels, we speculate that OPG may have both a protective function against inflammation and anti-angiogenic effects on adipose tissue.     

Interleukin-6 production in human subcutaneous abdominal adipose tissue: the effect of exercise

The interleukin-6 (IL-6) output from subcutaneous, abdominal adipose tissue was studied in nine healthy subjects before, during and for 3 h after 1 h two-legged bicycle exercise at 60 % maximal oxygen consumption. Seven subjects were studied in control experiments without exercise. The adipose tissue IL-6 output was measured by direct Fick technique. An artery and a subcutaneous vein on the anterior abdominal wall were catheterized. Adipose tissue blood flow was measured using the ¹³³Xe-washout method. In both studies there was a significant IL-6 output in the basal state and no significant change was observed during exercise. Post-exercise the IL-6 output began to increase after 30 min. Three hours post-exercise it was 58.6 ± 22.2 pg (100 g)⁻¹ min⁻¹. In the control experiments the IL-6 output also increased, but it only reached a level of 3.5 ± 0.8 pg (100 g)⁻¹ min⁻¹. The temporal profile of the post-exercise change in the IL-6 output closely resembles the changes in the outputs of glycerol and fatty acids, which we have described previously in the same adipose tissue depot. The difference is that it begins to increase ≈30 min before the glycerol and fatty acid outputs begin to increase. Thus, we suggest that the enhanced IL-6 production post-exercise in abdominal, subcutaneous adipose tissue may act locally via autocrine/paracrine mechanisms influencing lipolysis and fatty acid mobilization rate from this lipid depot.     

Deiodinating activity in the brown adipose tissue of rats following short cold exposure after strenuous exercise

Interscapular brown adipose tissue (IBAT) activity is controlled by the sympathetic nervous system, and factors that influence thermogenesis appear to act centrally to modify the sympathetic outflow to IBAT. Cold exposure produces a rise in IBAT temperature as a result of the increase in sympathetic outflow to IBAT. This is associated with an increased thyroid activity. 3,5,3'-triiodothyronine (T3) and T4 levels increase during strenuous exercise, and, at the end of the exercise bout, a decrease of T3 and T4 levels, with an increase in TSH during the following 4-5 days, is seen. We evaluated the effect of strenuous exercise on 5'-deiodinase (5'-D) activity in IBAT in normal environmental conditions and after short (30 min) cold exposure. 5'-D activity is lower in rats at basal condition. Short cold exposure (SCE) increases 5'-D in IBAT both in exercising rats and in sedentary rats. However, this increase is lower in exercising animals. Strenuous exercise can reduce 5'-D activity in normal environmental conditions and after SCE. Probably, other compensatory mechanisms of heat production are active in exercising rodents.     

Physical activity changes the regulation of mitochondrial respiration in human skeletal muscle

Electrophysiological and pharmacological properties of glycine receptors were characterized in hippocampal organotypic slice cultures. In the presence of ionotropic glutamate and GABA_B receptor antagonists, pressure-application of glycine onto CA3 pyramidal cells induced a current associated with increased chloride conductance, which was inhibited by strychnine. Similar chloride currents could also be induced with β-alanine or taurine. Whole-cell glycine responses were significantly greater in CA3 pyramidal cells than in CA1 pyramidal cells and dentate granule cells, while responses to GABA were similar among these three cell types. Although these results demonstrate the presence of functional glycine receptors in the hippocampus, no evidence for their activation during synaptic stimulation was found. Gabazine, a selective GABA_A receptor antagonist, totally blocked evoked IPSCs in CA3 pyramidal cells. Glycine receptor activation is not dependent on transporter-controlled levels of extracellular glycine, as no chloride current was observed in response to sarcosine, an inhibitor of glycine transporters. In contrast, application of guanidinoethanesulfonic acid, an uptake inhibitor of β-alanine and taurine, induced strychnine-sensitive chloride current in the presence of gabazine. These data indicate that modulation of transporters for the endogenous amino acids, β-alanine and taurine, can regulate tonic activation of glycine receptors, which may function in maintenance of inhibitory tone in the hippocampus.     

Lipolytic activity of adipose tissue in children

Bulletin of Experimental Biology and Medicine -     

Gene expression in human brown adipose tissue

Brown adipose tissue (BAT) has profound effects on body weight and metabolism in rodents. Recent reports show that human adults have significant amounts of BAT. Our aim was to study the gene expression profile of human BAT. Biopsies of adipose tissue with brown-red color and subcutaneous white adipose tissue (WAT) were obtained from 24 patients undergoing surgery in the thyroid region. Intrascapular BAT and epididymal WAT biopsies were obtained from 10 mice. Expression was analyzed by DNA microarray, real-time PCR and immunohistochemistry. Using the expression of the brown adipocyte-specific gene uncoupling protein 1 (UCP1) as a marker, approximately half of the human brown-red adipose tissue biopsies taken in the thyroid region contained BAT, and the presence of cells with brown adipocyte morphology was also verified by histology. Microarray analysis of 9 paired human BAT and WAT samples showed that 17 genes had at least a 4-fold higher expression in BAT compared to WAT and five of them (CKMT1, KCNK3, COBL, HMGCS2, TGM2) were verified using real-time PCR (P<0.05 for all). In addition, immunohistochemistry showed that the UCP1, KCNK3 and CKMT1 proteins are expressed in brown adipocytes. Except for UCP1 and KCNK3, the genes overexpressed in human BAT were not overexpressed in mouse BAT compared to mouse WAT. Our analysis identified genes that are differentially expressed in human BAT compared to WAT. The results also show that there are species-specific differences in BAT gene expression and this emphasizes the need for further molecular characterization of human BAT to clarify the mechanisms involved in regulated heat production in humans.     

Absence of humoral mediated 5'AMP-activated protein kinase activation in human skeletal muscle and adipose tissue during exercise

5'AMP-activated protein kinase (AMPK) exists as a heterotrimer comprising a catalytic α subunit and regulatory β and γ subunits. The AMPK system is activated under conditions of cellular stress, indicated by an increase in the AMP/ATP ratio, as observed, e.g. in muscles during contractile activity. AMPK was originally thought to be activated only by local intracellular mechanisms. However, recently it has become apparent that AMPK in mammals is also regulated by humoral substances, e.g. catecholamines. We studied whether humoral factors released during exercise regulate AMPK activity in contracting and resting muscles as well as in abdominal subcutaneous adipose tissue in humans. In resting leg muscle and adipose tissue the AMPK activity was not up-regulated by humoral factors during one-legged knee extensor exercise even when arm cranking exercise, inducing a ∼20-fold increase in plasma catecholamine level, was added simultaneously. In exercising leg muscle the AMPK activity was increased by one-legged knee extensor exercise eliciting a whole body respiratory load of only 30%     but was not further increased by adding arm cranking exercise. In conclusion, during exercise with combined leg kicking and arm cranking, the AMPK activity in human skeletal muscle is restricted to contracting muscle without influence of marked increased catecholamine levels. Also, with this type of exercise the catecholamines or other humoral factors do not seem to be physiological regulators of AMPK in the subcutaneous adipose tissue.     

Human adipose tissue blood flow during prolonged exercise II

Subcutaneous and perirenal adipose tissue blood flows (ATBF) were measured by the¹³³Xe washout method before, during and after 4 h exercise on a bicycle ergometer. The load corresponded to about 50% of max (i.e. about 1.7l/min). Subcutaneous and perirenal ATBF increased at an average to 3–400 and 700% of their initial control values respectively. In six of nine measuring sites ATBF remained increased in the hour following work. During work plasma glycerol concentrations increased 8 fold. The core temperature increased 0.9°C, skin temperature did not change significantly. During passive elevation of body temperature (core temperature +1.5°C; skin temperature +3°C) neither subcutaneous ATBF nor plasma glycerol concentrations changed significantly. It is concluded that the increase in subcutaneous ATBF during exercise is not a reaction to increased body temperature.