scholarly journals Phosphatidic acid and phosphatidylinositol labelling in adipose tissue. The role of endogenously formed adenosine

1983 ◽  
Vol 212 (2) ◽  
pp. 499-506 ◽  
Author(s):  
R J Schimmel ◽  
T W Honeyman ◽  
K K McMahon
Keyword(s):  
Adipose Tissue ◽  
Phosphatidic Acid ◽  
Adenosine Deaminase ◽  
Prostaglandin E1 ◽  
Time Course ◽  
Fat Cells ◽  
Inhibitory Effects ◽  
Selective Agonist ◽  
Adenosine Analogue

Incorporation of [32P]Pi into phosphatidic acid and phosphatidylinositol of hamster epididymal adipocytes was partially inhibited by 3-isobutyl-1-methylxanthine. This effect of 3-isobutyl-1-methylxanthine was antagonized by isopropyl-N6-phenyladenosine but not by 2′,5′-dideoxyadenosine, prostaglandin E1 or clonidine. N6-Phenylisopropyladenosine did not affect incorporation of [32P]Pi into phosphatidic acid or phosphatidylinositol when 3-isobutyl-1-methylxanthine was not present. In contrast with 3-isobutyl-1-methylxanthine inhibition of [32P]Pi incorporation into phospholipids, which was blocked only by N6-phenylisopropyladenosine, accelerated lipolysis was blocked by prostaglandin E1, clonidine and 2′,5′-dideoxyadenosine as well as by N6-phenylisopropyladenosine. Phospholipid labelling was also decreased in the presence of adenosine deaminase, but not in the presence of isoprenaline (isoproterenol). The stimulatory effect of N6-phenylisopropyladenosine on [32P]Pi incorporation into phospholipids in cells exposed to 3-isobutyl-1-methylxanthine was evident as soon as 3 min after addition of the adenosine analogue and maximum 10 min after its addition. As observed by others, [32P]Pi incorporation into phospholipids was increased by the alpha 1-selective agonist methoxamine. The stimulatory effect of methoxamine occurred with a time course similar to that of N6-phenylisopropyladenosine and was present at nearly equal magnitude in the absence or presence of 3-isobutyl-1-methylxanthine. The inhibitory effects of 3-isobutyl-1-methylxanthine and adenosine deaminase on phospholipid labelling are attributed to blockade of the action, or to the enzymic removal, of adenosine formed in and released from the fat-cells during their incubation. Supporting this view is the selective reversal of the actions of 3-isobutyl-1-methylxanthine and of adenosine deaminase by N6-phenylisopropyladenosine. These findings suggest an important role for endogenous adenosine in regulation of phospholipid turnover in adipocytes.

scholarly journals Adenosine and the control of lipolysis in rat adipocytes during pregnancy and lactation

1983 ◽  
Vol 216 (1) ◽  
pp. 121-128 ◽  
Author(s):  
R G Vernon ◽  
E Finley ◽  
E Taylor
Keyword(s):  
Adipose Tissue ◽  
Cell Volume ◽  
Adenosine Deaminase ◽  
Stromal Cells ◽  
Male Rats ◽  
Fat Cells ◽  
Pregnant Rats ◽  
Mean Cell Volume ◽  
Pregnancy And Lactation ◽  
Adenosine Analogue

The rate of noradrenaline-stimulated lipolysis is lower in fat-cells from lactating than from pregnant rats; this difference is eliminated by the addition of adenosine deaminase [Aitchison, Clegg & Vernon (1982) Biochem. J. 202, 243-247]. The activity of 5′-nucleotidase, and hence the capacity of the cells to synthesize adenosine, was the same in fat-cells and also stromal cells of adipose tissue from pregnant, lactating and male rats. The response and sensitivity of fat-cells to the anti-lipolytic effects of adenosine were measured by incubating cells in the presence of noradrenaline, adenosine deaminase (to remove endogenous adenosine) and various concentrations of the adenosine analogue N6-phenylisopropyladenosine (PIA). PIA caused a greater inhibition of the rate of noradrenaline-stimulated lipolysis in adipocytes from lactating than from pregnant rats. The concentration of PIA required to inhibit by 50% the rate of noradrenaline-stimulated lipolysis fell from over 100 nM for fat-cells from pregnant rats to 30 nM for fat-cells from lactating rats. The decreased rate of noradrenaline-stimulated lipolysis during lactation was not due to the smaller mean cell volume of adipocytes during this state.

scholarly journals Release of Inflammatory Mediators by Human Adipose Tissue Is Enhanced in Obesity and Primarily by the Nonfat Cells: A Review

2010 ◽  
Vol 2010 ◽  
pp. 1-20 ◽  
Author(s):  
John N. Fain
Keyword(s):  
Adipose Tissue ◽  
In Vitro Release ◽  
Human Adipose Tissue ◽  
Fat Cells ◽  
Omental Adipose Tissue ◽  
Subcutaneous Adipose ◽  
Circulating Levels ◽  
Pai 1

This paper considers the role of putative adipokines that might be involved in the enhanced inflammatory response of human adipose tissue seen in obesity. Inflammatory adipokines [IL-6, IL-10, ACE, TGFβ1, TNFα, IL-1β, PAI-1, and IL-8] plus one anti-inflammatory [IL-10] adipokine were identified whose circulating levels as well as in vitro release by fat are enhanced in obesity and are primarily released by the nonfat cells of human adipose tissue. In contrast, the circulating levels of leptin and FABP-4 are also enhanced in obesity and they are primarily released by fat cells of human adipose tissue. The relative expression of adipokines and other proteins in human omental as compared to subcutaneous adipose tissue as well as their expression in the nonfat as compared to the fat cells of human omental adipose tissue is also reviewed. The conclusion is that the release of many inflammatory adipokines by adipose tissue is enhanced in obese humans.

Role of adenosine as an endogenous regulator of respiration in hamster brown adipocytes

1984 ◽  
Vol 246 (3) ◽  
pp. C301-C307 ◽  
Author(s):  
R. J. Schimmel ◽  
L. McCarthy
Keyword(s):  
Adenylate Cyclase ◽  
Adenosine Deaminase ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Brown Adipocytes ◽  
Adenosine Receptor Antagonist ◽  
Endogenous Regulator ◽  
Camp Generation ◽  
Adenosine Analogue

The action of endogeneous adenosine on isolated hamster brown adipocytes was examined. Adenosine production from brown adipocytes was measured after labeling of the intracellular nucleotide pool with [3H]adenine. Accumulation of [3H]adenosine in the incubation medium was maximum after 5 min of incubation and was still present after 20 min. When adenosine accumulation was prevented by addition of adenosine deaminase, the stimulatory effects of isoproterenol on oxygen uptake, lipolysis, and adenosine 3',5'-cyclic monophosphate (cAMP) generation were enhanced. However, basal rates of lipolysis and oxygen consumption and levels of cAMP were not affected on addition of adenosine deaminase. A similar potentiation of isoproterenol responses was produced by the adenosine receptor antagonist, 3-isobutyl-1-methylxanthine, present at a concentration (10 microM) which did not change basal levels of respiration or lipolysis. Addition of the adenosine analogue 2-chloroadenosine antagonized isoproterenol-stimulated respiration and lipolysis and prevented potentiation of isoproterenol responses with 3-isobutyl-1-methylxanthine. To localize the site of adenosine action, activity of adenylate cyclase in membrane preparations from brown adipocytes was measured. Isoproterenol-stimulated adenylate cyclase activity was partially inhibited by 2-chloroadenosine in a GTP-dependent manner. Addition of Na+ enhanced the inhibitory effect of 2-chloroadenosine, and 3-isobutyl-1-methylxanthine blocked it. The calculated 50% effective dose for 2-chloroadenosine inhibition was between 10 and 15 nM. These data suggest that adenosine produced by brown adipocytes is an endogenous regulator of respiration in these cells acting at the level of the adenylate cyclase enzyme.

Coexistence of beta 1-, beta 2-, and beta 3-adrenoceptors in dog fat cells and their differential activation by catecholamines

1993 ◽  
Vol 264 (3) ◽  
pp. E403-E412 ◽  
Author(s):  
J. Galitzky ◽  
M. Reverte ◽  
M. Portillo ◽  
C. Carpene ◽  
M. Lafontan ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Fat Cells ◽  
Adrenergic Agonists ◽  
Differential Activation ◽  
Selective Agonist ◽  
Lipolytic Effect ◽  
Low Concentrations ◽  
Cgp 12177 ◽  
Beta 2 ◽  
Brl 37344

The existence of a beta 3-adrenoceptor (in addition to classical beta 1- and beta 2-), its involvement in the control of lipolysis and its recruitment by catecholamines were investigated in dog adipose tissue. Isoproterenol, norepinephrine, and the beta 2-selective agonist procaterol fully activated lipolysis in adipocytes (order of potency: isoproterenol > norepinephrine = procaterol). beta 3-Adrenergic agonists stimulated lipolysis with the order of potency: BRL 37344 > CGP 12177 > SR 58611A. Propranolol and bupranolol (nonselective beta-antagonists) antagonized, with a low potency, the effect of BRL 37344, whereas the beta 1-antagonist CGP 20712A and the beta 2-antagonist ICI 118551 were without action. CGP 20712A inhibited the effect of lower concentrations of agonists (0.05 microM isoproterenol, 0.1 microM norepinephrine and 0.1 microM procaterol) with an inhibitory constant (mean Ki) of 0.0075, 0.032 and > 10 microM, respectively. Mean Ki values for the beta 2-antagonist ICI 118551 were 1.744, 1.243, and 0.019 microM. This result indicates that low concentrations of isoproterenol and norepinephrine stimulate lipolysis mainly via beta 1-adrenoceptors in dog fat cells. Inversely, the lipolytic effect of higher concentrations of agonists i.e., 1 microM isoproterenol and catecholamines, was weakly antagonized by CGP 20712A or ICI 118551 while the nonselective beta-antagonists bupranolol and propranolol suppressed the effects with the order of potency expected for a beta 3-adrenoceptor: bupranolol > propranolol. These data indicate 1) the presence of a functional beta 3-adrenoceptor that coexists with beta 1- and beta 2-adrenoceptors in dog fat cells; 2) a separation of the differential potencies of physiological amines in the activation of lipolysis through beta 1-, beta 2-, and beta 3-adrenoceptors; the lipolytic response initiated at low concentrations (submicromolar range) of norepinephrine is primarily mediated by the beta 1-adrenoceptor subtype; and 3) an activation of the beta 3-adrenoceptor that occurs at higher concentrations of catecholamines.

scholarly journals Adipokines and Osteoarthritis: Novel Molecules Involved in the Pathogenesis and Progression of Disease

Arthritis ◽  
2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Javier Conde ◽  
Morena Scotece ◽  
Rodolfo Gómez ◽  
Veronica Lopez ◽  
Juan Jesus Gómez-Reino ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Risk Factor ◽  
White Adipose Tissue ◽  
Molecular Mechanisms ◽  
Mechanical Load ◽  
Critical Role ◽  
Fat Cells ◽  
Mechanical Effects ◽  
Progression Of Disease

Obesity has been considered a risk factor for osteoarthritis and it is usually accepted that obesity contributes to the development and progression of osteoarthritis by increasing mechanical load of the joints. Nevertheless, recent advances in the physiology of white adipose tissue evidenced that fat cells produce a plethora of factors, called adipokines, which have a critical role in the development of ostearthritis, besides to mechanical effects. In this paper, we review the role of adipokines and highlight the cellular and molecular mechanisms at play in osteoarthritis elicited by adipokines. We also emphasize how defining the role of adipokines has broadned our understanding of the diversity of factors involved in the genesis and progression of osteoarthritis in the hope of modifying it to prevent and treat diseases.

Time course of incorporation of n-3 PUFA from linseed in pigs and effects on D9-desaturase activity and pork odours

2001 ◽  
Vol 2001 ◽  
pp. 71-71
Author(s):  
M. Kouba ◽  
M. Enser ◽  
G.R. Nute ◽  
F.M. Whittington ◽  
J.D. Wood ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Adipose Tissue ◽  
Polyunsaturated Fatty Acids ◽  
Time Course ◽  
Desaturase Activity ◽  
Monounsaturated Fatty Acids ◽  
Lipid Classes ◽  
Inhibitory Effects ◽  
Tissue Lipids ◽  
Feeding Sources

The n-3 polyunsaturated fatty acids (PUFA) are healthy nutrients which can be increased in pork by feeding sources such as linseed to the growing animal. The levels achieved depend on many factors such as the concentrations of lipid classes in tissues (eg phospholipids containing high PUFA levels are more abundant in muscle than adipose tissue) competition for incorporation with n-6 PUFA and possible inhibitory effects of PUFA on synthesis of saturated and monounsaturated fatty acids. This study examined the time course of the incorporation of n-3 PUFA into tissue lipids and the effects on the major synthetic enzyme D9-desaturase. The effects on pork odour were also studied.

scholarly journals Gene deletion reveals roles for annexin A1 in the regulation of lipolysis and IL-6 release in epididymal adipose tissue

2006 ◽  
Vol 291 (6) ◽  
pp. E1264-E1273 ◽  
Author(s):  
James P. Warne ◽  
Christopher D. John ◽  
Helen C. Christian ◽  
John F. Morris ◽  
Roderick J. Flower ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Gene Deletion ◽  
Cell Number ◽  
Receptor Expression ◽  
Epididymal Adipose Tissue ◽  
Wild Type ◽  
Inhibitory Effects ◽  
Tissue Mass

In this study, epididymal adipose tissue from male annexin 1 (ANXA1)-null and wild-type control mice were used to explore the potential role of ANXA1 in adipocyte biology. ANXA1 was detected by Western blot analysis in wild-type tissue and localized predominantly to the stromal-vascular compartment. Epididymal fat pad mass was reduced by ANXA1 gene deletion, but adipocyte size was unchanged, suggesting that ANXA1 is required for the maintenance of adipocyte and/or preadipocyte cell number. Epididymal tissue from wild-type mice responded in vitro to noradrenaline and isoprenaline with increased glycerol release, reduced IL-6 release, and increased cAMP accumulation. Qualitatively similar but significantly attenuated responses to the catecholamines were observed in tissue from ANXA1-null mice, an effect that was not associated with changes in β-adrenoceptor mRNA expression. Lipopolysaccharide (LPS) also stimulated lipolysis in vitro, but its effects were muted by ANXA1 gene deletion. By contrast, LPS failed to influence IL-6 release from wild-type tissue but stimulated the release of the cytokine from tissue from ANXA1-null mice. ANXA1 gene deletion did not affect glucocorticoid receptor expression or the ability of dexamethasone to suppress catecholamine-induced lipolysis. It did, however, augment IL-6 expression and modify the inhibitory effects of glucocorticoids on IL-6 release. Collectively, these studies suggest that ANXA1 supports aspects of adipose tissue mass and alters the sensitivity of epididymal adipose tissue to catecholamines, glucocorticoids, and LPS, thereby modulating lipolysis and IL-6 release.

scholarly journals Changes in the anti-lipolytic action and binding to plasma membranes of N6-L-phenylisopropyladenosine in adipocytes from starved and hypothyroid rats

1984 ◽  
Vol 223 (1) ◽  
pp. 53-59 ◽  
Author(s):  
P Chohan ◽  
C Carpenter ◽  
E D Saggerson
Keyword(s):  
Adipose Tissue ◽  
Adenosine Deaminase ◽  
Binding Sites ◽  
Plasma Membranes ◽  
High Concentration ◽  
Lipolytic Action ◽  
Increased Sensitivity ◽  
Adipose Tissue Lipolysis ◽  
Adenosine Analogue ◽  
Adipocyte Plasma Membranes

The anti-lipolytic effect of the adenosine analogue N6-L-phenylisopropyladenosine was studied with rat adipocytes incubated with a high concentration of adenosine deaminase (0.5 unit/ml, approx. 2.5 micrograms/ml) and concentrations of noradrenaline that were equieffective in different physiological states. These studies were performed to compare the fed and starved (24h) states and to compare a hypothyroid state (induced by feeding propylthiouracil + a low-iodine diet) with the euthyroid state. Starvation increased sensitivity of the cells to the lipolytic action of noradrenaline, while decreasing sensitivity to the antilipolytic action of phenylisopropyladenosine. Hypothyroidism resulted in decreased sensitivity to noradrenaline and increased sensitivity to phenylisopropyladenosine. Studies of the binding of [3H]phenylisopropyladenosine to adipocyte plasma membranes indicated heterogeneity of binding sites or negative co-operativity in the binding. Starvation did not change [3H]phenylisopropyladenosine binding to membranes, whereas hypothyroidism caused an unexpected decrease in both the number and affinity of the binding sites. These observations are discussed in terms of the dual regulation of adipose-tissue lipolysis by lipolytic and anti-lipolytic agents.

Effects of pertussis toxin treatment on metabolism in hamster brown adipocytes

1985 ◽  
Vol 249 (5) ◽  
pp. C456-C463 ◽  
Author(s):  
R. J. Schimmel ◽  
L. McCarthy ◽  
D. Dzierzanowski
Keyword(s):  
Adenylate Cyclase ◽  
Adenosine Deaminase ◽  
Pertussis Toxin ◽  
Insulin Action ◽  
Brown Fat ◽  
Fat Cells ◽  
Inhibitory Effects ◽  
Brown Adipocytes ◽  
Stimulation Of ◽  
Adrenergic Agent

This communication reports the effects of the exotoxin of Bordetella pertussis (pertussis toxin) on hamster brown fat cells. Pertussis toxin significantly increased the lipolytic and respiratory responses to isoproterenol but did not increase the basal rates of either of these processes. In contrast, the stimulation of respiration by the alpha-adrenergic agent phenylephrine was not altered by pertussis toxin. The inhibitory effects of adenosine on stimulated lipolysis, respiration, and adenylate cyclase activity were completely abolished by pertussis toxin, as was the ability of methylxanthines or adenosine deaminase to potentiate isoproterenol stimulation of respiration or lipolysis. These effects of pertussis toxin were associated with an ADP ribosylation of a single membrane protein having a molecular weight of approximately 41. These data demonstrate that pertussis toxin can prevent the inhibitory action of adenosine on brown fat cells and suggest that the effects of the nucleoside on these cells results from inhibition of adenylate cyclase. We further suggest that the enhanced responses to isoproterenol in pertussis-treated adipocytes results from a blockade of the action of endogenous adenosine. In addition to blocking adenosine action, pertussis toxin also abolished the antilipolytic effect of insulin. However, because the antilipolytic effect of insulin was prevented by adenosine deaminase and 3-isobutyl-1-methylxanthine and restored by 2-chloroadenosine, we conclude that insulin action on these cells is dependent on adenosine. Thus pertussis toxin blockade of insulin action appears to be secondary to blockade of adenosine action.

scholarly journals Exogenous phosphatidic acid reduces acetaminophen-induced liver injury in mice by activating the interleukin-6 – Hsp70 axis through inter-organ crosstalk

2020 ◽  
Author(s):  
Melissa M. Clemens ◽  
Stefanie Kennon-McGill ◽  
Joel H. Vazquez ◽  
Owen W. Stephens ◽  
Erich A. Peterson ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Liver Injury ◽  
Phosphatidic Acid ◽  
Liver Regeneration ◽  
Interleukin 6 ◽  
Protective Role ◽  
Adjunct Treatment ◽  
Jnk Activation ◽  
Apap Hepatotoxicity

AbstractWe previously demonstrated that endogenous phosphatidic acid (PA) promotes liver regeneration after acetaminophen (APAP) hepatotoxicity in mice. Based on that, we hypothesized that exogenous PA is also beneficial. To test that, we treated mice with a toxic APAP dose at 0 h, followed by PA or vehicle at multiple timepoints. We then collected blood and liver at 6, 24, and 52 h. Post-treatment with PA protected against liver injury at 6 h, and the combination of PA and N-acetyl-cysteine (NAC) further reduced injury compared to NAC alone. Interestingly, PA had no effect on major early mechanisms of APAP toxicity, including APAP bioactivation, oxidative stress, JNK activation, and mitochondrial damage. However, transcriptomics revealed that PA activated interleukin-6 (IL-6) signaling in the liver, and IL-6 was increased in serum from PA-treated mice. Furthermore, PA did not protect against APAP in IL-6-deficient mice. Additional experiments revealed that PA induced heat shock protein 70 (Hsp70) in the liver in WT mice but not in IL-6 KO mice. Furthermore, IL-6 expression increased 18-fold in adipose tissue after PA, indicating that adipose tissue is a likely source of the increased IL-6 due to PA treatment. Surprisingly, however, exogenous PA did not alter regeneration, despite the widely accepted role of IL-6 in liver repair. These data reinforce the protective role of IL-6 and Hsp70 in APAP hepatotoxicity, provide new insight into the role of IL-6 in liver regeneration, and indicate that exogenous PA or PA derivatives may one day be a useful adjunct treatment for APAP overdose with NAC.

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