scholarly journals Masoprocol decreases rat lipolytic activity by decreasing the phosphorylation of HSL

2000 ◽  
Vol 279 (3) ◽  
pp. E593-E600 ◽  
Author(s):  
Maya S. Gowri ◽  
Rakia K. Azhar ◽  
Fredric B. Kraemer ◽  
Gerald M. Reaven ◽  
Salman Azhar
Keyword(s):  
Adipose Tissue ◽  
Lipolytic Activity ◽  
Nordihydroguaiaretic Acid ◽  
Hormone Sensitive Lipase ◽  
Creosote Bush ◽  
Lipoxygenase Inhibitor ◽  
Serum Free Fatty Acid ◽  
In Vivo Experiments

Masoprocol (nordihydroguaiaretic acid), a lipoxygenase inhibitor isolated from the creosote bush, has been shown to decrease adipose tissue lipolytic activity both in vivo and in vitro. The present study was initiated to test the hypothesis that the decrease in lipolytic activity by masoprocol resulted from modulation of adipose tissue hormone-sensitive lipase (HSL) activity. The results indicate that oral administration of masoprocol to rats with fructose-induced hypertriglyceridemia significantly decreased their serum free fatty acid (FFA; P < 0.05), triglyceride (TG; P < 0.001), and insulin ( P < 0.05) concentrations. In addition, isoproterenol-induced lipolytic rate and HSL activity were significantly lower ( P < 0.001) in adipocytes isolated from masoprocol compared with vehicle-treated rats and was associated with a decrease in HSL protein. Incubation of masoprocol with adipocytes from chow-fed rats significantly inhibited isoproterenol-induced lipolytic activity and HSL activity, associated with a decrease in the ability of isoproterenol to phosphorylate HSL. Masoprocol had no apparent effect on adipose tissue phosphatidylinositol 3-kinase activity, but okadaic acid, a serine/threonine phosphatase inhibitor, blocked the antilipolytic effect of masoprocol. The results of these in vitro and in vivo experiments suggest that the antilipolytic activity of masoprocol is secondary to its ability to inhibit HSL phosphorylation, possibly by increasing phosphatase activity. As a consequence, masoprocol administration results in lower serum FFA and TG concentrations in hypertriglyceridemic rodents.

Abstract 064: The Lipoxigenase Inhibitor Nordihydroguaiaretic Acid Prevents the Development of Hypoxia-Induced Pulmonary Hypertension in Mice

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Andrea Iorga ◽  
Gabriel Wong ◽  
Denise Mai ◽  
Jingyuan Li ◽  
Salil Sharma ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Smooth Muscle ◽  
Smooth Muscle Actin ◽  
Nordihydroguaiaretic Acid ◽  
Treated Group ◽  
Oxidation Products ◽  
Lipoxygenase Inhibitor ◽  
Human Pulmonary Artery

Pulmonary hypertension (PH) is a chronic lung disease characterized by progressively elevated pulmonary arterial pressures and severe pulmonary vascular remodeling resulting from interactions between oxidized lipoprotein deposition and increased endothelial proliferation. Previously we have shown increased plasma levels of biological oxidation products such as hydroxyoctadecadienoic acids (HODEs) and hydroxyeicosatetraenoic acids (HETEs) in the rat monocrotaline model of PH. Here we investigated the role of HETEs and HODEs in the development of PH and whether their inhibition with the lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA) attenuates the progression of PH. Mice were placed in a hypoxic chamber with O2 concentrations of ≤10% for 21 days and either left untreated to develop PH (n=7) or treated with NDGA daily (10mg/kg/day, i.p., n=4) from day 1. Direct RV catheterization was terminally performed to record RV pressure (RVP). Pulmonary arteriolar thickening and oxidized lipid deposition were assessed by staining lung sections with Masson’s Trichrome or with α-smooth muscle actin and E-06 (marker for oxidized low-density lipoproteins). In vitro, human pulmonary artery smooth muscle cell (hPASMC) proliferation was assessed by MTT assays in the absence or presence of 12-HETE (100ng/ml), 9-HODE (1µg/ml) and 13-HODE (1µg/ml) alone or together with NDGA (10, 25 and 50µM). In-vitro, HETE/HODE treatment increased hPASMC proliferation ~ 2-fold when compared to untreated cells and NDGA significantly inhibited the proliferative effects of all three oxidized lipids. In-vivo, NDGA treatment prevented the development of PH. RVP was lower in the NDGA-treated group vs. the PH group (24.01±1.39mmHg vs. 36.91±5.74mmHg, p<0.05) and was comparable to control normoxic mice (20.93±2.52mmHg). RV hypertrophy index was significantly elevated in the PH mice versus control mice (0.38±0.03 vs. 0.28±0.02 (p<0.001), while NDGA treatment completely prevented the development of RV hypertrophy (0.28±0.04). Lung sections demonstrated arteriolar thickening and E-06 positive deposits in the PH group, which was prevented by NDGA therapy. We conclude that oxidized fatty acid deposition and accumulation might play a role in the development of PH.

Increased in vitro fatty acid supply and cellular transport capacities in cold-acclimated ducklings (Cairina moschata)

1998 ◽  
Vol 275 (3) ◽  
pp. R683-R690 ◽  
Author(s):  
Christophe Bénistant ◽  
Claude Duchamp ◽  
Frédérique Cohen-Adad ◽  
Jean-Louis Rouanet ◽  
Hervé Barré
Keyword(s):  
Adipose Tissue ◽  
Gastrocnemius Muscle ◽  
Lipolytic Activity ◽  
Binding Capacity ◽  
Cellular Transport ◽  
Transport Capacity ◽  
Nonesterified Fatty Acids ◽  
Cairina Moschata

In cold-acclimated (CA) birds, lipids play a crucial role in regulatory thermogenesis by acting both as substrates for and activators of thermogenic processes. The capacity to supply lipids to thermogenic tissues, which could limit cold thermogenesis, was assessed in CA ducklings (5 wk old, 4°C) and compared with thermoneutral controls (TN, 25°C). In CA ducklings, basal lipolytic activity of adipose tissue fragments was higher (202 ± 9 vs. 130 ± 14 nmol glycerol released ⋅ 100 mg tissue−1 ⋅ h−1, +55%) than in TN controls, while glucagon had a much higher stimulatory effect (+140 to +500% depending on dose). This was consistent with increased plasma levels of nonesterified fatty acids (FA, +57%) and glycerol (+31%) in vivo. In vitro endothelial lipase activity per organ was higher in CA than in TN ducklings in red gastrocnemius muscle (6.3 ± 0.6 vs. 3.5 ± 0.3 μeq nonesterified FA released per hour, +80%) and liver (+55%). The intracellular FA-binding capacity of (12–18 kDa) proteins was higher in gastrocnemius muscle (+43%) and liver (+74%) from CA ducklings. In gastrocnemius, it was linked to a higher content (21 ± 2 vs. 15 ± 2 μg/mg protein, +37%) of an intracellular 15.4-kDa FA-binding protein. These in vitro results indicate that coordinated increases in FA supply from adipose tissue, cellular uptake of lipoprotein-derived FA, and intracellular FA transport capacity occur in CA ducklings endowed with higher thermogenic capacity and cold endurance.

scholarly journals The Extract of Arctium lappa L. Fruit (Arctii Fructus) Improves Cancer-Induced Cachexia by Inhibiting Weight Loss of Skeletal Muscle and Adipose Tissue

Nutrients ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 3195
Author(s):  
Yo-Han Han ◽  
Jeong-Geon Mun ◽  
Hee Dong Jeon ◽  
Dae Hwan Yoon ◽  
Byung-Min Choi ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Weight Loss ◽  
Adipose Tissue ◽  
Cancer Cachexia ◽  
Uncoupling Protein ◽  
Body Weight Loss ◽  
In Vivo Experiments ◽  
Wasting Syndrome

Background: Cachexia induced by cancer is a systemic wasting syndrome and it accompanies continuous body weight loss with the exhaustion of skeletal muscle and adipose tissue. Cancer cachexia is not only a problem in itself, but it also reduces the effectiveness of treatments and deteriorates quality of life. However, effective treatments have not been found yet. Although Arctii Fructus (AF) has been studied about several pharmacological effects, there were no reports on its use in cancer cachexia. Methods: To induce cancer cachexia in mice, we inoculated CT-26 cells to BALB/c mice through subcutaneous injection and intraperitoneal injection. To mimic cancer cachexia in vitro, we used conditioned media (CM), which was CT-26 colon cancer cells cultured medium. Results: In in vivo experiments, AF suppressed expression of interleukin (IL)-6 and atrophy of skeletal muscle and adipose tissue. As a result, the administration of AF decreased mortality by preventing weight loss. In adipose tissue, AF decreased expression of uncoupling protein 1 (UCP1) by restoring AMP-activated protein kinase (AMPK) activation. In in vitro model, CM increased muscle degradation factors and decreased adipocytes differentiation factors. However, these tendencies were ameliorated by AF treatment in C2C12 myoblasts and 3T3-L1 cells. Conclusion: Taken together, our study demonstrated that AF could be a therapeutic supplement for patients suffering from cancer cachexia.

β-Adrenoceptors mediate inhibition of lipolysis in adipocytes of tilapia (Oreochromis mossambicus)

2002 ◽  
Vol 282 (2) ◽  
pp. E318-E325 ◽  
Author(s):  
Gerjanne J. Vianen ◽  
Peter P. Obels ◽  
Guido E. E. J. M. van den Thillart ◽  
Johan Zaagsma
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid ◽  
Free Fatty Acid ◽  
Plasma Free Fatty Acid ◽  
Oreochromis Mossambicus ◽  
Plasma Norepinephrine ◽  
In Vivo Experiments ◽  
First Time

The regulation of triglyceride mobilization by catecholamines was investigated in the teleost fish Oreochromis mossambicus (tilapia) in vivo and in vitro. In vitro experiments were carried out with adipocytes that were isolated for the first time from fish adipose tissue. For the in vivo experiments, cannulated tilapia were exposed to stepwise decreasing oxygen levels (20, 10, and 5% air saturation; 3.9, 1.9, and 1.0 kPa Po 2, respectively), each level being maintained for 2 h. Blood samples were taken at timed intervals and analyzed for plasma lactate, glucose, free fatty acids, epinephrine, norepinephrine, and cortisol. Hypoxia exposure did not change plasma epinephrine levels. In contrast, the plasma norepinephrine concentration markedly increased at all hypoxia levels. Over the same period, plasma free fatty acid levels showed a significant continuous decrease, suggesting that norepinephrine is responsible for the reduced plasma free fatty acid concentration, presumably through inhibition of lipolysis in adipose tissue. To elucidate the mechanism, adipocytes were isolated from mesenteric adipose tissue of tilapia and incubated with 1) norepinephrine, 2) norepinephrine + phentolamine (α1,α2-antagonist), 3) isoproterenol (nonselective β-agonist), 4) isoproterenol + timolol (β1,β2-antagonist), 5) norepinephrine + timolol, and 6) BRL-35135A (β3-agonist). The results demonstrate for the first time that norepinephrine and isoproterenol suppress lipolysis in isolated adipocytes of tilapia. The effect of norepinephrine is not mediated through α2-adrenoceptors but, like isoproterenol, via β-adrenoceptors. Furthermore, this study provides strong indications that β3-adrenoceptors are involved.

scholarly journals Genistein Induces Adipogenic and Autophagic Effects in Rainbow Trout (Oncorhynchus mykiss) Adipose Tissue: In Vitro and In Vivo Models

2020 ◽  
Vol 21 (16) ◽  
pp. 5884
Author(s):  
Sara Balbuena-Pecino ◽  
Esmail Lutfi ◽  
Natàlia Riera-Heredia ◽  
Esther Gasch-Navalón ◽  
Emilio J. Vélez ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Rainbow Trout ◽  
Lipid Metabolism ◽  
Oncorhynchus Mykiss ◽  
Fatty Acid Synthase ◽  
Hormone Sensitive Lipase ◽  
In Vivo Models ◽  
Rainbow Trout Oncorhynchus Mykiss

Soybeans are one of the most used alternative dietary ingredients in aquafeeds. However, they contain phytoestrogens like genistein (GE), which can have an impact on fish metabolism and health. This study aimed to investigate the in vitro and in vivo effects of GE on lipid metabolism, apoptosis, and autophagy in rainbow trout (Oncorhynchus mykiss). Primary cultured preadipocytes were incubated with GE at different concentrations, 10 or 100 μM, and 1 μM 17β-estradiol (E2). Furthermore, juveniles received an intraperitoneal injection of GE at 5 or 50 µg/g body weight, or E2 at 5 µg/g. In vitro, GE 100 μM increased lipid accumulation and reduced cell viability, apparently involving an autophagic process, indicated by the higher LC3-II protein levels, and higher lc3b and cathepsin d transcript levels achieved after GE 10 μM. In vivo, GE 50 µg/g upregulated the gene expression of fatty acid synthase (fas) and glyceraldehyde-3-phosphate dehydrogenase in adipose tissue, suggesting enhanced lipogenesis, whereas it increased hormone-sensitive lipase in liver, indicating a lipolytic response. Besides, autophagy-related genes increased in the tissues analyzed mainly after GE 50 µg/g treatment. Overall, these findings suggest that an elevated GE administration could lead to impaired adipocyte viability and lipid metabolism dysregulation in rainbow trout.

scholarly journals α-Conotoxins Enhance both the In Vivo Suppression of Ehrlich carcinoma Growth and In Vitro Reduction in Cell Viability Elicited by Cyclooxygenase and Lipoxygenase Inhibitors

Marine Drugs ◽  
2020 ◽  
Vol 18 (4) ◽  
pp. 193
Author(s):  
Alexey V. Osipov ◽  
Tatiana I. Terpinskaya ◽  
Tatsiana Yanchanka ◽  
Tatjana Balashevich ◽  
Maxim N. Zhmak ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Antitumor Effect ◽  
Nordihydroguaiaretic Acid ◽  
Ehrlich Carcinoma ◽  
Arachidonic Acid Cascade ◽  
Lipoxygenase Inhibitor ◽  
Lipoxygenase Inhibitors ◽  
Combined Application

Several biochemical mechanisms, including the arachidonic acid cascade and activation of nicotinic acetylcholine receptors (nAChRs), are involved in increased tumor survival. Combined application of inhibitors acting on these two pathways may result in a more pronounced antitumor effect. Here, we show that baicalein (selective 12-lipoxygenase inhibitor), nordihydroguaiaretic acid (non-selective lipoxygenase inhibitor), and indomethacin (non-selective cyclooxygenase inhibitor) are cytotoxic to Ehrlich carcinoma cells in vitro. Marine snail α-conotoxins PnIA, RgIA and ArIB11L16D, blockers of α3β2/α6β2, α9α10 and α7 nAChR subtypes, respectively, as well as α-cobratoxin, a blocker of α7 and muscle subtype nAChRs, exhibit low cytotoxicity, but enhance the antitumor effect of baicalein 1.4-fold after 24 h and that of nordihydroguaiaretic acid 1.8–3.9-fold after 48 h of cell cultivation. α-Conotoxin MII, a blocker of α6-containing and α3β2 nAChR subtypes, increases the cytotoxic effect of indomethacin 1.9-fold after 48 h of cultivation. In vivo, baicalein, α-conotoxins MII and PnIA inhibit Ehrlich carcinoma growth and increase mouse survival; these effects are greatly enhanced by the combined application of α-conotoxin MII with indomethacin or conotoxin PnIA with baicalein. Thus, we show, for the first time, antitumor synergism of α-conotoxins and arachidonic acid cascade inhibitors.

Control of adipose tissue lipolysis in ectotherm vertebrates

1992 ◽  
Vol 263 (4) ◽  
pp. R857-R862 ◽  
Author(s):  
R. H. Migliorini ◽  
J. S. Lima-Verde ◽  
C. R. Machado ◽  
G. M. Cardona ◽  
M. A. Garofalo ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Adenylate Cyclase ◽  
Lipolytic Activity ◽  
Adenylate Cyclase System ◽  
Triacylglycerol Lipase ◽  
Membrane Bound ◽  
Adipose Tissue Lipolysis ◽  
Toad Bufo

Lipolytic activity of fish (Hoplias malabaricus), toad (Bufo paracnemis), and snake (Philodryas patagoniensis) adipose tissue was investigated in vivo and in vitro. Catecholamines or glucagon did not affect the release of free fatty acids (FFA) by incubated fish and toad adipose tissue. Catecholamines also failed to activate snake adipose tissue lipolysis, which even decreased in the presence of epinephrine. However, glucagon stimulated both the lipolytic activity of reptilian tissue in vitro and the mobilization of FFA to plasma when administered to snakes in vivo. The release of FFA from incubated fish, amphibian, and reptilian adipose tissue increased markedly in the presence of cAMP or xanthine derivatives, inhibitors of phosphodiesterase. Forskolin or fluoride, activators of specific components of the adenylate cyclase system, strongly stimulated toad adipose tissue lipolysis. The data suggest that adipocyte triacylglycerol lipase of ectotherm vertebrates is activated by a cAMP-mediated phosphorylation and that the organization of the membrane-bound adenylate cyclase system is similar to that of mammals.

Abstract 3591: Group X sPLA2 Deficiency Increases Adiposity and Adipose Tissue Inflammation in Mice

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Nancy R Webb ◽  
Xia Li ◽  
Kathy Forrest ◽  
William Bailey ◽  
Boris B Boyanovsky ◽  
...  
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Lipolytic Activity ◽  
Fasting Blood Glucose ◽  
Tissue Expression ◽  
Adipose Tissue Inflammation ◽  
Tissue Inflammation ◽  
Mouse Tissues

Introduction: Of the 10 secretory phospholipase A 2 (sPLA 2 ) enzymes expressed in humans, Group X (GX) sPLA 2 is the most potent in hydrolyzing phospholipids on cell membranes. In addition to its lipolytic activity, GX sPLA 2 is also a high affinity ligand for the M-type sPLA 2 receptor. Although numerous studies have implicated GX sPLA 2 in important biological processes in vitro , data from studies in vivo are lacking. To elucidate the physiological functions of this enzyme we recently developed C57BL/6 mice with targeted deletion of the GX sPLA 2 gene. Results : Analysis by real time RT-PCR showed that GX sPLA 2 mRNA is widely distributed in mouse tissues, with highest expression in intestine, testes, brain, thymus, spleen, fat, lung, and heart. Unlike some of the other members of the sPLA 2 family, tissue expression of GX sPLA 2 was not highly upregulated in mice injected with lipopolysaccharide. However, GX sPLA 2 was induced almost 5-fold in retroperitoneal fat of mice fed a high-fat (60 kcal%) diet for 17 weeks.Targeted disruption of GX sPLA 2 resulted in increased body weight in 1.5 year-old mice fed a normal laboratory diet (male GX sPLA 2 +/+ mice: 35.8±0.4 g; male GX sPLA 2 −/− mice: 45.033.2 g; p<0.05). The increase in body weight was associated with significantly increased percent body fat (GX sPLA 2 +/+ mice: 16.0±1.0%; GX sPLA 2 −/− mice: 19.6±1%; p<0.05), increased adipocyte size (GX sPLA 2 +/+ mice: 1300±26 um 2 GX sPLA 2 −/− mice: 2700±78 um 2 ; p<0.001), and decreased fasting plasma triglyceride levels (GX sPLA 2 +/+ mice: 46.3±4.9 mg/dl; GX sPLA 2 −/− mice: 33.8±2.9 mg/dl; p<0.05) at 3 months of age. Food consumption, fasting blood glucose, and plasma total cholesterol levels were not significantly different between GX sPLA 2 −/− and GX sPLA 2 +/+ mice. Compared to 3 month old GX sPLA 2 +/+ mice, the relative expression of IL-6 and F4/80 mRNAs in adipose tissue of age-matched GX sPLA 2 −/− mice was increased 9- and 4-fold, respectively, suggesting that the increased adiposity in GX sPLA 2 −/− mice was associated with an increase in the inflammatory profile of adipose tissue Conclusions: Our data points to a previously unrecognized role for Group X sPLA 2 in the development of obesity and associated adipose tissue inflammation.

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