Diet-induced obesity, adipose inflammation, and metabolic dysfunction correlating with PAR2 expression are attenuated by PAR2 antagonism

Article

Lim, Junxian, Iyer, Abishek, Liu, Ligong, Suen, Jacky Y., Lohman, Rink-Jan, Seow, Vernon, Yau, Mei-Kwan, Brown, Lindsay and Fairlie, David P.. 2013. "Diet-induced obesity, adipose inflammation, and metabolic dysfunction correlating with PAR2 expression are attenuated by PAR2 antagonism." The FASEB Journal. 27 (12), pp. 4757-4767. https://doi.org/10.1096/fj.13-232702
Article Title

Diet-induced obesity, adipose inflammation, and metabolic dysfunction correlating with PAR2 expression are attenuated by PAR2 antagonism

ERA Journal ID2078
Article CategoryArticle
AuthorsLim, Junxian (Author), Iyer, Abishek (Author), Liu, Ligong (Author), Suen, Jacky Y. (Author), Lohman, Rink-Jan (Author), Seow, Vernon (Author), Yau, Mei-Kwan (Author), Brown, Lindsay (Author) and Fairlie, David P. (Author)
Journal TitleThe FASEB Journal
Journal Citation27 (12), pp. 4757-4767
Number of Pages11
Year2013
Place of PublicationBethesda, MD. United States
ISSN0892-6638
1530-6860
Digital Object Identifier (DOI)https://doi.org/10.1096/fj.13-232702
Web Address (URL)http://www.fasebj.org/content/27/12/4757.abstract
Abstract

Excessive uptake of fatty acids and glucose by adipose tissue triggers adipocyte dysfunction and infiltration of immune cells. Altered metabolic homeostasis in adipose tissue promotes insulin resistance, type 2 diabetes, hypertension, and cardiovascular disease. Inflammatory and metabolic processes are mediated by certain proteolytic enzymes that share a common cellular target, protease-activated receptor 2 (PAR2). This study showed that human and rat obesity correlated in vivo with increased expression of PAR2 in adipose tissue, primarily in stromal vascular cells (SVCs) including macrophages. PAR2 was expressed more than other PARs on human macrophages and was increased by dietary fatty acids (palmitic, stearic, and myristic). A novel PAR2 antagonist, GB88 (5-isoxazoyl- Cha-Ile-spiroindene-1,4-piperidine), given orally at 10 mg/kg/d (wk 8-16) reduced body weight by 10% in obese rats fed a high-carbohydrate high-fat (HCHF) diet for 16 wk, and strongly attenuated adiposity, adipose tissue inflammation, infiltrated macrophages and mast cells, insulin resistance, and cardiac fibrosis and remodeling; while reversing liver and pancreatic dysfunction and normalizing secretion of PAR2-directed glucose-stimulated insulin secretion in MIN6 cells. In summary, PAR2 is a new biomarker for obesity, and its expression is stimulated by dietary fatty acids; PAR2 is a substantial contributor to inflammatory and metabolic dysfunction; and a PAR2 antagonist inhibits diet-induced obesity and inflammatory, metabolic, and cardiovascular dysfunction.

KeywordsaAdipocyte; biomarker; inhibitor; macrophage; protease-activated receptor
ANZSRC Field of Research 2020320507. Metabolic medicine
321004. Nutritional science
321401. Basic pharmacology
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Byline AffiliationsUniversity of Queensland
Department of Biological and Physical Sciences
Institution of OriginUniversity of Southern Queensland
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Wong, Weng-Yew and Brown, Lindsay. 2014. "Induction of metabolic syndrome by excess fructose consumption." Turan, Belma and Dhalla, Naranjan S. (ed.) Diabetic cardiomyopathy: biochemical and molecular mechanisms. New York, NY. United States. Springer. pp. 41-63
A green algae mixture of Scenedesmus and Schroederiella attenuates obesity-linked metabolic syndrome in rats
Kumar, Senthil Arun, Magnusson, Marie, Ward, Leigh C., Paul, Nicholas A. and Brown, Lindsay. 2015. "A green algae mixture of Scenedesmus and Schroederiella attenuates obesity-linked metabolic syndrome in rats." Nutrients. 7 (4), pp. 2771-2787. https://doi.org/10.3390/nu7042771
Prebiotics in obesity
Carnahan, S., Balzer, A., Panchal, S. K. and Brown, L.. 2014. "Prebiotics in obesity." Panminerva Medica. 56 (2), pp. 165-175.
Increased progression to kidney fibrosis after erythropoietin is used as a treatment for acute kidney injury
Gobe, Glenda C., Bennett, Nigel C., West, Malcolm, Colditz, Paul, Brown, Lindsay, Vesey, David A. and Johnson, David W.. 2014. "Increased progression to kidney fibrosis after erythropoietin is used as a treatment for acute kidney injury." American Journal of Physiology: Renal Physiology. 306 (6), pp. F681-F692. https://doi.org/10.1152/ajprenal.00241.2013
Seaweed supplements normalise metabolic, cardiovascular and liver responses in high-carbohydrate, high-fat fed rats
Kumar, Senthil Arun, Magnusson, Marie, Ward, Leigh C., Paul, Nicholas A. and Brown, Lindsay. 2015. "Seaweed supplements normalise metabolic, cardiovascular and liver responses in high-carbohydrate, high-fat fed rats." Marine Drugs. 13 (2), pp. 788-805. https://doi.org/10.3390/md13020788
Nutraceuticals for chronic inflammatory diseases
Brown, Lindsay. 2013. "Nutraceuticals for chronic inflammatory diseases." Journal of the Australian Traditional-Medicine Society. 19 (4), pp. 214-221.
Obesity and metabolic syndrome
Panchal, Sunil K., Bhaswant, Maharshu and Brown, Lindsay. 2014. "Obesity and metabolic syndrome." Vela, Jose M., Maldonado, Rafael and Hamon, Michel (ed.) In vivo models for drug discovery. Weinheim, Germany. John Wiley & Sons. pp. 333-348
Glibenclamide improves kidney and heart structure and function in the adenine-diet model of chronic kidney disease
Diwan, Vishal, Gobe, Glenda and Brown, Lindsay. 2014. "Glibenclamide improves kidney and heart structure and function in the adenine-diet model of chronic kidney disease." Pharmacological Research. 79, pp. 104-110. https://doi.org/10.1016/j.phrs.2013.11.007
Gender differences in adenine-induced chronic kidney disease and cardiovascular complications in rats
Diwan, Vishal, Small, David, Kauter, Kate, Gobe, Glenda C. and Brown, Lindsay. 2014. "Gender differences in adenine-induced chronic kidney disease and cardiovascular complications in rats." American Journal of Physiology: Renal Physiology. 307 (11), pp. F1169-F1178. https://doi.org/10.1152/ajprenal.00676.2013
Effects of red pitaya juice supplementation on cardiovascular and hepatic changes in high-carbohydrate, high-fat diet-induced metabolic syndrome rats
Ramli, Nurul Shazini, Brown, Lindsay, Ismail, Patimah and Rahmat, Asmah. 2014. "Effects of red pitaya juice supplementation on cardiovascular and hepatic changes in high-carbohydrate, high-fat diet-induced metabolic syndrome rats." BMC Complementary Medicine and Therapies. 14, pp. 189-198. https://doi.org/10.1186/1472-6882-14-189
Food as medicine [Introduction]
Panchal, Sunil K., Ward, Leigh C. and Brown, Lindsay. 2013. "Food as medicine [Introduction]." Canadian Journal of Physiology and Pharmacology. 91 (6), pp. 503-503. https://doi.org/10.1139/cjpp-2013-0147
Osteoporosis and its association with non-gonadal hormones involved in hypertension, adiposity and hyperglycaemia
Poudyal, Hemant and Brown, Lindsay. 2013. "Osteoporosis and its association with non-gonadal hormones involved in hypertension, adiposity and hyperglycaemia." Current Drug Targets. 14 (14), pp. 1694-1706. https://doi.org/10.2174/1389450119999990001
Seaweeds as potential therapeutic interventions for the metabolic syndrome
Kumar, Senthil Arun and Brown, Lindsay. 2013. "Seaweeds as potential therapeutic interventions for the metabolic syndrome." Reviews in Endocrine and Metabolic Disorders. 14 (3), pp. 299-308. https://doi.org/10.1007/s11154-013-9254-8
Atrial arrhythmia in ageing spontaneously hypertensive rats: unraveling the substrate in hypertension and ageing
Lau, Dennis H., Shipp, Nicholas J., Kelly, Darren J., Thanigaimani, Shivshankar, Neo, Melissa, Kuklik, Pawel, Lim, Han S., Zhang, Yuan, Drury, Karen, Wong, Christopher X., Chia, Nicholas H., Brooks, Anthony G., Dimitri, Hany, Saint, David A., Brown, Lindsay and Sanders, Prashanthan. 2013. "Atrial arrhythmia in ageing spontaneously hypertensive rats: unraveling the substrate in hypertension and ageing." PLoS One. 8 (8), pp. 1-9. https://doi.org/10.1371/journal.pone.0072416
Adenine-induced chronic kidney and cardiovascular damage in rats
Diwan, Vishal, Mistry, Anand, Gobe, Glenda and Brown, Lindsay. 2013. "Adenine-induced chronic kidney and cardiovascular damage in rats." Journal of Pharmacological and Toxicological Methods. 68 (2), pp. 197-207. https://doi.org/10.1016/j.vascn.2013.05.006
Chronic l-arginine treatment improves metabolic, cardiovascular and liver complications in diet-induced obesity in rats
Alam, Md. Ashraful, Kauter, Kathleen, Withers, Kerry, Sernia, Conrad and Brown, Lindsay. 2013. "Chronic l-arginine treatment improves metabolic, cardiovascular and liver complications in diet-induced obesity in rats." Food and Function. 4 (1), pp. 83-91. https://doi.org/10.1039/c2fo30096f
Naringin improves diet-induced cardiovascular dysfunction and obesity in high carbohydrate, high fat diet-fed rats
Alam, Md. Ashraful, Kauter, Kathleen and Brown, Lindsay. 2013. "Naringin improves diet-induced cardiovascular dysfunction and obesity in high carbohydrate, high fat diet-fed rats." Nutrients. 5 (3), pp. 637-650. https://doi.org/10.3390/nu5030637
C5aR and C3aR antagonists each inhibit diet-induced obesity, metabolic dysfunction, and adipocyte and macrophage signaling
Lim, Junxian, Iyer, Abishek, Suen, Jacky Y., Seow, Vernon, Reid, Robert C., Brown, Lindsay and Fairlie, David P.. 2013. "C5aR and C3aR antagonists each inhibit diet-induced obesity, metabolic dysfunction, and adipocyte and macrophage signaling." The FASEB Journal. 27 (2), pp. 822-831. https://doi.org/10.1096/fj.12-220582
Ferulic acid improves cardiovascular and kidney structure and function in hypertensive rats
Alam, Md. Ashraful, Sernia, Conrad and Brown, Lindsay. 2013. "Ferulic acid improves cardiovascular and kidney structure and function in hypertensive rats." Journal of Cardiovascular Pharmacology. 61 (3), pp. 240-249. https://doi.org/10.1097/FJC.0b013e31827cb600
Responses to oleic, linoleic and alpha linolenic acids in high-carbohydrate, high-fat diet-induced metabolic syndrome in rats
Poudyal, Hemant, Kumar, Senthil A., Iyer, Aarjit, Waanders, Jennifer, Ward, Leigh C. and Brown, Lindsay. 2013. "Responses to oleic, linoleic and alpha linolenic acids in high-carbohydrate, high-fat diet-induced metabolic syndrome in rats." Journal of Nutritional Biochemistry. 24 (7), pp. 1381-1392. https://doi.org/10.1016/j.jnutbio.2012.11.006
Effects of ALA, EPA and DHA in high-carbohydrate, high-fat diet-induced metabolic syndrome in rats
Poudyal, Hemant, Panchal, Sunil K., Ward, Leigh C. and Brown, Lindsay. 2013. "Effects of ALA, EPA and DHA in high-carbohydrate, high-fat diet-induced metabolic syndrome in rats ." Journal of Nutritional Biochemistry. 24 (6), pp. 1041-1052. https://doi.org/10.1016/j.jnutbio.2012.07.014
Tocotrienols as possible treatments for obesity
Wong, Weng-Yew and Brown, Lindsay. 2013. "Tocotrienols as possible treatments for obesity." Tan, Barrie, Watson, Ronald Ross and Preedy, Victor R. (ed.) Tocotrienols: vitamin E beyond tocopherols, 2nd ed.. Boca Raton, FL. United States. CRC Press. pp. 195-208
The role of n-3 polyunsaturated fatty acids in human heart failure
Poudyal, Hemant and Brown, Lindsay. 2013. "The role of n-3 polyunsaturated fatty acids in human heart failure." Endocrine, Metabolic and Immune Disorders: Drug Targets. 13 (1), pp. 105-117. https://doi.org/10.2174/1871530311313010013
Traditional Indian medicines for metabolic syndrome
Diwan, Vishal, Poudyal, Hemant and Brown, Lindsay. 2012. "Traditional Indian medicines for metabolic syndrome." Essa, M. Mohamed, Manickavasagan, A. and Sukumar, E. (ed.) Natural products and their active compounds on disease prevention. Hauppauge, NY. United States . Nova Science Publishers. pp. 1-21
Tocotrienols reverse cardiovascular, metabolic and liver changes in high carbohydrate, high fat diet-fed rats
Wong, Weng-Yew, Poudyal, Hemant, Ward, Leigh C. and Brown, Lindsay. 2012. "Tocotrienols reverse cardiovascular, metabolic and liver changes in high carbohydrate, high fat diet-fed rats." Nutrients. 4 (10), pp. 1527-1541. https://doi.org/10.3390/nu4101527
Endurance exercise in a rat model of metabolic syndrome
Cameron, Isabelle, Alam, Mohammed Ashraful, Wang, Jianxiong and Brown, Lindsay. 2012. "Endurance exercise in a rat model of metabolic syndrome." Canadian Journal of Physiology and Pharmacology. 90 (11), pp. 1490-1497. https://doi.org/10.1139/y2012-097
Chronic high-carbohydrate, high-fat feeding in rats induces reversible metabolic, cardiovascular, and liver changes
Poudyal, Hemant, Panchal, Sunil K., Ward, Leigh C., Waanders, Jennifer and Brown, Lindsay. 2012. "Chronic high-carbohydrate, high-fat feeding in rats induces reversible metabolic, cardiovascular, and liver changes ." American Journal of Physiology: Endocrinology and Metabolism. 302 (12), pp. 1472-1482. https://doi.org/10.1152/ajpendo.00102.2012
Caffeine attenuates metabolic syndrome in diet-induced obese rats
Panchal, Sunil K., Wong, Weng-Yew, Kauter, Kate, Ward, Leigh C. and Brown, Lindsay. 2012. "Caffeine attenuates metabolic syndrome in diet-induced obese rats." Nutrition. 28 (10), pp. 1055-1062. https://doi.org/10.1016/j.nut.2012.02.013
An inhibitor of phospholipase A2 group IIA modulates adipocyte signaling and protects against diet-induced metabolic syndrome in rats
Iyer, Abishek, Lim, Junxian, Poudyal, Hemant, Reid, Robert C., Suen, Jacky Y., Webster, Julie, Prins, Johannes B., Whitehead, Jonathan P., Fairlie, David P. and Brown, Lindsay. 2012. "An inhibitor of phospholipase A2 group IIA modulates adipocyte signaling and protects against diet-induced metabolic syndrome in rats." Diabetes. 61 (9), pp. 2320-2329. https://doi.org/10.2337/db11-1179
Lysine acetylation in obesity, diabetes and metabolic disease
Iyer, Abishek, Fairlie, David P. and Brown, Lindsay. 2012. "Lysine acetylation in obesity, diabetes and metabolic disease ." Immunology and Cell Biology. 90 (1), pp. 39-46. https://doi.org/10.1038/icb.2011.99
Coffee extract attenuates changes in cardiovascular and hepatic structure and function without decreasing obesity in high-carbohydrate, high-fat diet-fed male rats
Panchal, Sunil K., Poudyal, Hemant, Waanders, Jennifer and Brown, Lindsay. 2012. "Coffee extract attenuates changes in cardiovascular and hepatic structure and function without decreasing obesity in high-carbohydrate, high-fat diet-fed male rats ." The Journal of Nutrition. 142 (4), pp. 690-697. https://doi.org/10.3945/jn.111.153577
Lipid redistribution by alpha linolenic acid-rich chia seed inhibits stearoyl-CoA desaturase-1 and induces cardiac and hepatic protection in diet-induced obese rats
Poudyal, Hemant, Panchal, Sunil K., Waanders, Jennifer, Ward, Leigh and Brown, Lindsay. 2012. "Lipid redistribution by alpha linolenic acid-rich chia seed inhibits stearoyl-CoA desaturase-1 and induces cardiac and hepatic protection in diet-induced obese rats." Journal of Nutritional Biochemistry. 23 (2), pp. 153-162. https://doi.org/10.1016/j.jnutbio.2010.11.011
The effects of immunosuppressants on vascular function, systemic oxidative stress and inflammation in rats
Shing, Cecilia M., Fassett, Robert G., Brown, Lindsay and Coombes, Jeff S.. 2012. "The effects of immunosuppressants on vascular function, systemic oxidative stress and inflammation in rats." Transplant International. 25 (3), pp. 337-346. https://doi.org/10.1111/j.1432-2277.2011.01420.x
Quercetin ameliorates cardiovascular, hepatic, and metabolic changes in diet-induced metabolic syndrome in rats
Panchal, Sunil K., Poudyal, Hemant and Brown, Lindsay. 2012. "Quercetin ameliorates cardiovascular, hepatic, and metabolic changes in diet-induced metabolic syndrome in rats ." The Journal of Nutrition. 142 (6), pp. 1026-1032. https://doi.org/10.3945/jn.111.157263
Mitogen-activated protein kinase and natural phenolic compounds in cardiovascular remodeling
Alam, Md. Ashraful, Uddin, Shaikh Jamal and Brown, Lindsay. 2012. "Mitogen-activated protein kinase and natural phenolic compounds in cardiovascular remodeling ." Rahman, Atta (ed.) Bioactive natural products. Amsterdam, Netherlands. Elsevier. pp. 159-190
Mineralocorticoid receptors mediate cardiac remodelling in morphine-dependent rats
Mesripour, Azadeh, Iyer, Abishek and Brown, Lindsay. 2012. "Mineralocorticoid receptors mediate cardiac remodelling in morphine-dependent rats." Basic and Clinical Pharmacology and Toxicology. 111 (2), pp. 75-80. https://doi.org/10.1111/j.1742-7843.2012.00860.x
Piperine attenuates cardiovascular, liver and metabolic changes in high carbohydrate, high fat-fed rats
Diwan, Vishal, Poudyal, Hemant and Brown, Lindsay. 2013. "Piperine attenuates cardiovascular, liver and metabolic changes in high carbohydrate, high fat-fed rats ." Cell Biochemistry and Biophysics. 67 (2), pp. 297-304. https://doi.org/10.1007/s12013-011-9306-1
Ellagic acid attenuates high-carbohydrate, high-fat diet-induced metabolic syndrome in rats
Panchal, Sunil K., Ward, Leigh and Brown, Lindsay. 2013. "Ellagic acid attenuates high-carbohydrate, high-fat diet-induced metabolic syndrome in rats." European Journal of Nutrition. 52 (2), pp. 559-568. https://doi.org/10.1007/s00394-012-0358-9
Cardioprotective and hepatoprotective effects of ellagitannins from European oak bark (Quercus petraea L.) extract in rats
Panchal, Sunil K. and Brown, Lindsay. 2013. "Cardioprotective and hepatoprotective effects of ellagitannins from European oak bark (Quercus petraea L.) extract in rats." European Journal of Nutrition. 52 (1), pp. 397-408. https://doi.org/10.1007/s00394-011-0277-1
Gender differences in metabolic syndrome - a key research issue
Iyer, Abishek, Kauter, Kathleen and Brown, Lindsay. 2011. "Gender differences in metabolic syndrome - a key research issue." Endocrine, Metabolic and Immune Disorders: Drug Targets. 11 (3), pp. 182-188.
Stearoyl-CoA desaturase: a vital checkpoint in the development and progression of obesity
Poudyal, Hemant and Brown, Lindsay. 2011. "Stearoyl-CoA desaturase: a vital checkpoint in the development and progression of obesity." Endocrine, Metabolic and Immune Disorders: Drug Targets. 11 (3), pp. 217-231.
Nutrapharmacology of tocotrienols for metabolic syndrome
Wong, Weng-Yew and Brown, Lindsay. 2011. "Nutrapharmacology of tocotrienols for metabolic syndrome ." Current Pharmaceutical Design. 17 (21), pp. 2206-2214. https://doi.org/10.2174/138161211796957445
Omega-3 fatty acids and metabolic syndrome: effects and emerging mechanisms of action
Poudyal, Hemant, Panchal, Sunil K., Diwan, Vishal and Brown, Lindsay. 2011. "Omega-3 fatty acids and metabolic syndrome: effects and emerging mechanisms of action." Progress in Lipid Research. 50 (4), pp. 372-387. https://doi.org/10.1016/j.plipres.2011.06.003
Inhibition of inflammation and fibrosis by a complement C5a receptor antagonist in DOCA-salt hypertensive rats
Iyer, Abishek, Woodruff, Trent M., Wu, Mike C. L., Stylianou, Con, Reid, Robert C., Fairlie, David P., Taylor, Stephen M. and Brown, Lindsay. 2011. "Inhibition of inflammation and fibrosis by a complement C5a receptor antagonist in DOCA-salt hypertensive rats ." Journal of Cardiovascular Pharmacology. 58 (5), pp. 479-486. https://doi.org/10.1097/FJC.0b013e31822a7a09
Pharmacological inhibition of soluble epoxide hydrolase ameliorates diet-induced metabolic syndrome in rats
Iyer, Abishek, Kauter, Kathleen, Alam, Md. Ashraful, Hwang, Sung Hee, Morisseau, Christophe, Hammock, Bruce D. and Brown, Lindsay. 2012. "Pharmacological inhibition of soluble epoxide hydrolase ameliorates diet-induced metabolic syndrome in rats." Experimental Diabetes Research. 2012, pp. 1-11. https://doi.org/10.1155/2012/758614
Chronic b-adrenoceptor antagonist treatment controls cardiovascular remodeling in heart failure in the aging spontaneously hypertensive rat
Chan, Vincent, Fenning, Andrew, Hoey, Andrew and Brown, Lindsay. 2011. "Chronic b-adrenoceptor antagonist treatment controls cardiovascular remodeling in heart failure in the aging spontaneously hypertensive rat." Journal of Cardiovascular Pharmacology. 58 (4), pp. 424-431. https://doi.org/10.1097/FJC.0b013e3182283c78
Coffee and caffeine attenuate symptoms of metabolic syndrome in diet-induced obese rats
Panchal, S. and Brown, L.. 2012. "Coffee and caffeine attenuate symptoms of metabolic syndrome in diet-induced obese rats." 2012 Australian & New Zealand Obesity Society Annual Scientific Meeting. New Zealand 01 Oct 2012 Netherlands. https://doi.org/10.1016/j.orcp.2012.08.039
The streptozotocin-diabetic rat as a model of the chronic complications of human diabetes
Wei, Michael, Ong, Leslie, Smith, Maree, Ross, Fraser B., Schmid, Katrina, Hoey, Andrew, Burstow, Darryl and Brown, Lindsay. 2003. "The streptozotocin-diabetic rat as a model of the chronic complications of human diabetes." Heart Lung and Circulation. 12 (1), pp. 44-50. https://doi.org/10.1046/j.1444-2892.2003.00160.x
Attenuation of Cardiovascular Remodeling in DOCA-Salt Rats by the Vasopeptidase Inhibitor, Omapatrilat
Loch, David, Hoey, Andrew and Brown, Lindsay. 2006. "Attenuation of Cardiovascular Remodeling in DOCA-Salt Rats by the Vasopeptidase Inhibitor, Omapatrilat ." Clinical and Experimental Hypertension. 28 (5), pp. 475-488. https://doi.org/10.1080/10641960600798754
Alterations in dihydropyridine receptors in dystrophin-deficient cardiac muscle
Woolf, Peter James, Lu, Sai, Cornford-Nairn, Renee A., Watson, Michael, Xiao, Xiao-Hui, Holroyd, Sean, Brown, Lindsay and Hoey, Andrew. 2006. "Alterations in dihydropyridine receptors in dystrophin-deficient cardiac muscle." American Journal of Physiology: Heart and Circulatory Physiology. 290 (6), pp. H2439-H2445. https://doi.org/10.1152/ajpheart.00844.2005
Cardiac extracellular matrix: a dynamic entity
Brown, Lindsay. 2005. "Cardiac extracellular matrix: a dynamic entity." American Journal of Physiology: Heart and Circulatory Physiology. 289 (3), pp. H973-H974. https://doi.org/10.1152/ajpheart.00443.2005
Increased calcium influx mediates increased cardiac stiffness in hyperthyroid rats
Levick, Scott, Fenning, Andrew and Brown, Lindsay. 2005. "Increased calcium influx mediates increased cardiac stiffness in hyperthyroid rats." Cell Biochemistry and Biophysics. 43 (1), pp. 53-60.
Antioxidant supplementation enhances erythrocyte antioxidant status and attenuates cyclosporine-induced vascular dysfunction
Lexis, L. A., Fenning, A., Brown, L., Fassett, R. G. and Coombes, J. S.. 2006. "Antioxidant supplementation enhances erythrocyte antioxidant status and attenuates cyclosporine-induced vascular dysfunction." American Journal of Transplantation. 6 (1), pp. 41-49. https://doi.org/10.1111/j.1600-6143.2005.01154.x
Therapeutic interventions: an Islamic perspective
Rahman, Mohammad Tariqur, Nazer, Reeza, Brown, Lindsay, Shogar, Ibrahim and Bouzenita, Anke Iman. 2008. "Therapeutic interventions: an Islamic perspective." IMA Journal. 40 (2), pp. 60-68.
Antifibrotic activity of an inhibitor of group IIA secretory phospholipase A2 in young spontaneously hypertensive rats
Levick, Scott, Loch, David, Rolfe, Barbara E., Reid, Robert C., Fairlie, David P., Taylor, Stephen M. and Brown, Lindsay. 2006. "Antifibrotic activity of an inhibitor of group IIA secretory phospholipase A2 in young spontaneously hypertensive rats ." Journal of Immunology. 176 (11), pp. 7000-7007.
Pre-existing inflammatory state compromises heat tolerance in rats exposed to heat stress
Lim, Chin Leong, Wilson, Gary, Brown, Lindsay, Coombes, Jeff S. and Mackinnon, Laurel T.. 2007. "Pre-existing inflammatory state compromises heat tolerance in rats exposed to heat stress ." American Journal of Physiology: Regulatory, Integrative and Comparative Physiology. 292 (1), pp. R186-R194. https://doi.org/10.1152/ajpregu.00921.2005
Obesity and hypertension have differing oxidant handling molecular pathways in age-related chronic kidney disease
Percy, C. J., Brown, Lindsay, Power, D. A., Johnson, David W. and Gobe, Glenda C.. 2009. "Obesity and hypertension have differing oxidant handling molecular pathways in age-related chronic kidney disease." Mechanisms of Ageing and Development. 130 (3), pp. 129-138. https://doi.org/10.1016/j.mad.2008.10.003
Chronic dietary L-arginine down-regulates adenosine receptor and nitric oxide synthase expression in rat heart
Rose'Meyer, Roselyn B., Harrison, Glenn, Fenning, Andrew, Jenner, Tamsin and Brown, Lindsay. 2008. "Chronic dietary L-arginine down-regulates adenosine receptor and nitric oxide synthase expression in rat heart." Basic and Clinical Pharmacology and Toxicology. 102 (5), pp. 459-465. https://doi.org/10.1111/j.1742-7843.2008.00209.x
Resistance to ocular antibiotics: an overview
Brown, Lindsay. 2007. "Resistance to ocular antibiotics: an overview ." Clinical and Experimental Optometry. 90 (4), pp. 258-262. https://doi.org/10.1111/j.1444-0938.2007.00154.x
Rutin attenuates metabolic changes, nonalcoholic steatohepatitis, and cardiovascular remodeling in high-carbohydrate, high-fat diet-fed rats
Panchal, Sunil K., Poudyal, Hemant, Arumugam, Thiruma V. and Brown, Lindsay. 2011. "Rutin attenuates metabolic changes, nonalcoholic steatohepatitis, and cardiovascular remodeling in high-carbohydrate, high-fat diet-fed rats ." The Journal of Nutrition. 141 (6), pp. 1062-1069. https://doi.org/10.3945/jn.111.137877
High-carbohydrate, high-fat diet-induced metabolic syndrome and cardiovascular remodeling in rats
Panchal, Sunil K., Poudyal, Hemant, Iyer, Abishek, Nazer, Reeza, Alam, Md. Ashraful, Diwan, Vishal, Kauter, Kathleen, Sernia, Conrad, Campbell, Fiona, Ward, Leigh, Gobe, Glenda, Fenning, Andrew and Brown, Lindsay. 2011. "High-carbohydrate, high-fat diet-induced metabolic syndrome and cardiovascular remodeling in rats." Journal of Cardiovascular Pharmacology. 57 (5), pp. 611-624. https://doi.org/10.1097/FJC.0b013e3181feb90a
A regenerative antioxidant protocol of vitamin E and alpha-lipoic acid ameliorates cardiovascular and metabolic changes in fructose-fed rats
Patel, Jatin, Matnor, Nur Azim, Iyer, Abishek and Brown, Lindsay. 2011. "A regenerative antioxidant protocol of vitamin E and alpha-lipoic acid ameliorates cardiovascular and metabolic changes in fructose-fed rats." Evidence-Based Complementary and Alternative Medicine. https://doi.org/10.1155/2011/120801
Cardiovascular changes during maturation and ageing in male and female spontaneously hypertensive rats
Chan, Vincent, Fenning, Andrew, Levick, Scott P., Loch, David, Chunduri, Prasad, Iyer, Abishek, Teo, Yi Ling, Hoey, Andrew, Wilson, Kathleen, Burstow, Darryl and Brown, Lindsay. 2011. "Cardiovascular changes during maturation and ageing in male and female spontaneously hypertensive rats." Journal of Cardiovascular Pharmacology. 57 (4), pp. 469-478. https://doi.org/10.1097/FJC.0b013e3182102c3b
Resveratrol improves cardiovascular function in DOCA-salt hypertensive rats
Chan, Vincent, Fenning, Andrew, Iyer, Abishek, Hoey, Andrew and Brown, Lindsay. 2011. "Resveratrol improves cardiovascular function in DOCA-salt hypertensive rats." Current Pharmaceutical Biotechnology. 12 (3), pp. 429-436. https://doi.org/10.2174/138920111794480552
Rodent models for metabolic syndrome research
Panchal, Sunil K. and Brown, Lindsay. 2011. "Rodent models for metabolic syndrome research." Journal of Biomedicine and Biotechnology. https://doi.org/10.1155/2011/351982
Comparison of purple carrot juice and b-carotene in a high-carbohydrate, high-fat diet-fed rat model of the metabolic syndrome
Poudyal, Hemant, Panchal, Sunil and Brown, Lindsay. 2010. "Comparison of purple carrot juice and b-carotene in a high-carbohydrate, high-fat diet-fed rat model of the metabolic syndrome." The British Journal of Nutrition: an international journal of nutritional science. 104 (9), pp. 1322-1332. https://doi.org/10.1017/S0007114510002308
Lipid mediators and inflammation in glucose intolerance and insulin resistance
Iyer, Abishek and Brown, Lindsay. 2010. "Lipid mediators and inflammation in glucose intolerance and insulin resistance." Drug Discovery Today: Disease Mechanisms. 7 (3-4), pp. e191-e197. https://doi.org/10.1016/j.ddmec.2010.12.001
The DOCA-salt hypertensive rat as a model of cardiovascular oxidative and inflammatory stress
Iyer, Abishek, Chan, Vincent and Brown, Lindsay. 2010. "The DOCA-salt hypertensive rat as a model of cardiovascular oxidative and inflammatory stress." Current Cardiology Reviews. 6 (4), pp. 291-297. https://doi.org/10.2174/157340310793566109
Green tea attenuates cardiovascular remodeling and metabolic symptoms in high carbohydrate-fed rats
Rickman, Celestine, Iyer, Abishek, Chan, Vincent and Brown, Lindsay. 2010. "Green tea attenuates cardiovascular remodeling and metabolic symptoms in high carbohydrate-fed rats." Current Pharmaceutical Biotechnology. 11 (8), pp. 881-886.
The cardiovascular nutrapharmacology of resveratrol: pharmacokinetics, molecular mechanisms and therapeutic potential
Kroon, Paul A., Iyer, Abishek, Chunduri, Prasad, Chan, Vincent and Brown, Lindsay. 2010. "The cardiovascular nutrapharmacology of resveratrol: pharmacokinetics, molecular mechanisms and therapeutic potential ." Current Medicinal Chemistry. 17 (23), pp. 2442-2455. https://doi.org/10.2174/092986710791556032
L-carnitine attenuates cardiac impairment but not vascular dysfunction in DOCA-salt hypertensive rats
O'Brien, Daniel, Chunduri, Prasad, Iyer, Abishek and Brown, Lindsay. 2010. "L-carnitine attenuates cardiac impairment but not vascular dysfunction in DOCA-salt hypertensive rats ." Basic and Clinical Pharmacology and Toxicology. 106 (4), pp. 296-301. https://doi.org/10.1111/j.1742-7843.2009.00480.x
Rutin attenuates non-alcoholic steatohepatitis in high carbohydrate-high fat diet-fed rats
Panchal, S. K., Poudyal, H., Arumugam, T. V. and Brown, L.. 2011. "Rutin attenuates non-alcoholic steatohepatitis in high carbohydrate-high fat diet-fed rats." 46th Annual Meeting of the European Association for the Study of the Liver. Berlin 30 Mar - 03 Apr 2011 Netherlands. https://doi.org/10.1016/S0168-8278(11)60097-4
Portal pressure responses and angiotensin peptide production in rat liver are determined by relative activity of ACE and ACE2
Herath, Chandana B., Lubel, John S., Jia, Zhiyuan, Velkoska, Elena, Casley, David, Brown, Lindsay, Tikellis, Chris, Burrell, Louise M. and Angus, Peter W.. 2009. "Portal pressure responses and angiotensin peptide production in rat liver are determined by relative activity of ACE and ACE2." American Journal of Physiology: Gastrointestinal and Liver Physiology. 297 (1), pp. G98-G106. https://doi.org/10.1152/ajpgi.00045.2009
Antifibrotic activity of an inhibitor of histone deacetylases in DOCA-salt hypertensive rats: research paper
Iyer, Abishek, Fenning, Andrew, Lim, Junxian, Le, Giang T., Reid, Robert C., Halili, Maria A., Fairlie, David P. and Brown, Lindsay. 2010. "Antifibrotic activity of an inhibitor of histone deacetylases in DOCA-salt hypertensive rats: research paper." British Journal of Pharmacology. 159 (7), pp. 1408-1417. https://doi.org/10.1111/j.1476-5381.2010.00637.x
Inflammatory lipid mediators in adipocyte function and obesity
Iyer, Abishek, Prins, Johannes B., Fairlie, David P., Hammock, Bruce D. and Brown, Lindsay. 2010. "Inflammatory lipid mediators in adipocyte function and obesity." Nature Reviews Endocrinology. 6 (2), pp. 71-82. https://doi.org/10.1038/nrendo.2009.264
Is mycophenolate more than just an immunosuppressant? An overview
Iyer, Abishek and Brown, Lindsay. 2009. "Is mycophenolate more than just an immunosuppressant? An overview." Indian Journal of Biochemistry and Biophysics. 46 (1), pp. 25-30.
Evaluation of the chronic complications of diabetes in a high fructose diet in rats
Patel, Jatin, Iyer, Abishek and Brown, Lindsay. 2009. "Evaluation of the chronic complications of diabetes in a high fructose diet in rats." Indian Journal of Biochemistry and Biophysics. 46 (1), pp. 66-72.
The biological responses to resveratrol and other polyphenols from alcoholic beverages
Brown, Lindsay, Kroon, Paul A., Das, Dipak K., Das, Samarjit, Tosaki, Arpad, Chan, Vincent, Singer, Manfred V. and Feick, Peter. 2009. "The biological responses to resveratrol and other polyphenols from alcoholic beverages." Alcoholism: Clinical and Experimental Research. 33 (9), pp. 1513-1523. https://doi.org/10.1111/j.1530-0277.2009.00989.x
Potential health benefits of Indian spices in the symptoms of metabolic syndrome: a review
Iyer, Abishek, Panchal, Sunil, Poudyal, Hemant and Brown, Lindsay. 2009. "Potential health benefits of Indian spices in the symptoms of metabolic syndrome: a review." Indian Journal of Biochemistry and Biophysics. 46 (6), pp. 467-481.
Fermented wheat germ extract extract (Avemar) in the treatment of cardiac remodelling and metabolic symptoms in rats
Iyer, Abishek and Brown, Lindsay. 2009. "Fermented wheat germ extract extract (Avemar) in the treatment of cardiac remodelling and metabolic symptoms in rats." Evidence-Based Complementary and Alternative Medicine. 2011, pp. 1-9. https://doi.org/10.1093/ecam/nep090
Cardiovascular effects of the toxin(s) of the Australian paralysis tick, Ixodes holocyclus, in the rat
Campbell, Fiona, Atwell, Rick, Fenning, Andrew, Hoey, Andrew and Brown, Lindsay. 2004. "Cardiovascular effects of the toxin(s) of the Australian paralysis tick, Ixodes holocyclus, in the rat." Toxicon. 43 (7), pp. 743-750. https://doi.org/10.1016/j.toxicon.2004.02.025
Olive leaf extract attenuates cardiac, hepatic, and metabolic changes in high carbohydrate-, high fat-fed rats
Poudyal, Hemant, Campbell, Fiona and Brown, Lindsay. 2010. "Olive leaf extract attenuates cardiac, hepatic, and metabolic changes in high carbohydrate-, high fat-fed rats." The Journal of Nutrition. 140 (5), pp. 946-953. https://doi.org/10.3945/jn.109.117812
Rosuvastatin attenuates heart failure and cardiac remodelling in the ageing spontaneously hypertensive rat
Loch, David, Chan, Vincent, Hoey, Andrew and Brown, Lindsay. 2009. "Rosuvastatin attenuates heart failure and cardiac remodelling in the ageing spontaneously hypertensive rat." Basic and Clinical Pharmacology and Toxicology. 105 (4), pp. 262-270. https://doi.org/10.1111/j.1742-7843.2009.00440.x
Prevention of hypertension in DOCA-salt rats by an inhibitor of soluble epoxide hydrolase
Loch, David, Hoey, Andrew, Morisseau, Christophe, Hammock, Bruce O. and Brown, Lindsay. 2007. "Prevention of hypertension in DOCA-salt rats by an inhibitor of soluble epoxide hydrolase." Cell Biochemistry and Biophysics. 47 (1), pp. 87-98.
Rosuvastatin attenuates hypertension-induced cardiovascular remodeling without affecting blood pressure in DOCA-salt hypertensive rats
Loch, David, Levick, Scott, Hoey, Andrew and Brown, Lindsay. 2006. "Rosuvastatin attenuates hypertension-induced cardiovascular remodeling without affecting blood pressure in DOCA-salt hypertensive rats." Journal of Cardiovascular Pharmacology. 47 (3), pp. 396-404.
Improved cardiovascular function with aminoguanidine in DOCA-salt hypertensive rats
Chan, Vincent, Hoey, Andrew and Brown, Lindsay. 2006. "Improved cardiovascular function with aminoguanidine in DOCA-salt hypertensive rats." British Journal of Pharmacology. 148 (7), pp. 902-908. https://doi.org/10.1038/sj.bjp.0706801
L-Arginine attenuates cardiovascular impairment in DOCA-salt hypertensive rats
Fenning, Andrew, Harrison, Glenn, Rose'Meyer, Roselyn, Hoey, Andrew and Brown, Lindsay. 2005. "L-Arginine attenuates cardiovascular impairment in DOCA-salt hypertensive rats." American Journal of Physiology: Heart and Circulatory Physiology. 289 (4), pp. H1408-H1416. https://doi.org/10.1152/ajpheart.00140.2005
Reversal of cardiac dysfunction by selective ET-A receptor antagonism
Allan, Anthony, Fenning, Andrew, Levick, Scott, Hoey, Andrew and Brown, Lindsay. 2005. "Reversal of cardiac dysfunction by selective ET-A receptor antagonism." British Journal of Pharmacology. 146 (6), pp. 846-853. https://doi.org/10.1038/sj.bjp.0706384