Sympathetic denervation

To further understand how sympathetic nerves influence PVAT function, we could use sympathetic denervation of PVAT surrounding hind limb skeletal muscle arteries. In brief, the left sympathetic chain is removed from L2 to the bifurcation of the abdominal aorta (Griffith & Farris, 1942). This process will not affect sympathetic innervation of any other organs, and will not affect motor function of the limb. The procedure could be carried out approximately three weeks before sacrifice, and the function of the PVAT surrounding these hind limb arteries could be studied using wire myography; the unaffected opposite hind limb would be used as a control. We hypothesise that sympathetic denervation will lead to a loss of PVAT function similar to what is seen in obesity.

162

References

Abdelaal AA & Mohamad MA. (2015). Obesity indices and haemodynamic response to exercise in obese diabetic hypertensive patients: Randomized controlled trial. Obes Res Clin

Pract9, 475-486.

Aghamohammadzadeh R, Greenstein AS, Yadav R, Jeziorska M, Hama S, Soltani F, Pemberton PW, Ammori B, Malik RA, Soran H & Heagerty AM. (2013). Effects of bariatric surgery on human small artery function: evidence for reduction in perivascular adipocyte inflammation, and the restoration of normal anticontractile activity despite persistent obesity. J Am Coll Cardiol62, 128-135.

Aghamohammadzadeh R & Heagerty AM. (2012). Obesity-related hypertension: epidemiology, pathophysiology, treatments, and the contribution of perivascular adipose tissue. Ann Med44 Suppl 1, S74-84.

Alexander S, Kelly E, Marrion N, Peters J, Benson H, Faccenda E, Pawson A, Sharman J, Southan C, Davies J & Collaborators C. (2015). Concise Guide to PHARMACOLOGY 2015/16: Transporters, pp. 6110-6202. Br J Pharmacol.

Almabrouk TA, Ugusman AB, Katwan OJ, Salt IP & Kennedy S. (2016). Deletion of AMPKalpha1 attenuates the anticontractile effect of perivascular adipose tissue (PVAT) and reduces adiponectin release. Br J Pharmacol.

Alnouti Y, Petrick JS & Klaassen CD. (2006). Tissue distribution and ontogeny of organic cation transporters in mice. Drug Metab Dispos34, 477-482.

Altman DG & Bland JM. (1997). Statistics notes. Units of analysis. Bmj314, 1874.

Anderson EA, Sinkey CA & Mark AL. (1991). Mental stress increases sympathetic nerve activity during sustained baroreceptor stimulation in humans. Hypertension17, Iii43-49.

Arch JR. (2002). beta(3)-Adrenoceptor agonists: potential, pitfalls and progress. Eur J

Pharmacol440, 99-107.

Arita Y, Kihara S, Ouchi N, Takahashi M, Maeda K, Miyagawa J, Hotta K, Shimomura I, Nakamura T, Miyaoka K, Kuriyama H, Nishida M, Yamashita S, Okubo K, Matsubara K, Muraguchi M, Ohmoto Y, Funahashi T & Matsuzawa Y. (1999). Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem Biophys Res Commun

257, 79-83.

Astrup A, Andersen T, Christensen NJ, Bulow J, Madsen J, Breum L & Quaade F. (1990). Impaired glucose-induced thermogenesis and arterial norepinephrine response persist after weight reduction in obese humans. Am J Clin Nutr51, 331-337.

Ayala-Lopez N, Jackson WF, Burnett R, Wilson JN, Thompson JM & Watts SW. (2015). Organic cation transporter 3 contributes to norepinephrine uptake into perivascular adipose tissue. Am J Physiol Heart Circ Physiol309, H1904-1914.

163 Ayala-Lopez N, Martini M, Jackson WF, Darios E, Burnett R, Seitz B, Fink GD & Watts SW. (2014). Perivascular adipose tissue contains functional catecholamines. Pharmacol Res

Perspect2, e00041.

Bamshad M, Aoki VT, Adkison MG, Warren WS & Bartness TJ. (1998). Central nervous system origins of the sympathetic nervous system outflow to white adipose tissue. Am J Physiol

275, R291-299.

Bane V, Lehane M, Dikshit M, O'Riordan A & Furey A. (2014). Tetrodotoxin: chemistry, toxicity, source, distribution and detection. Toxins (Basel)6, 693-755.

Barrett EJ, Eggleston EM, Inyard AC, Wang H, Li G, Chai W & Liu Z. (2009). The vascular actions of insulin control its delivery to muscle and regulate the rate-limiting step in skeletal muscle insulin action. Diabetologia52, 752-764.

Barry VW, Baruth M, Beets MW, Durstine JL, Liu J & Blair SN. (2014). Fitness vs. fatness on all- cause mortality: a meta-analysis. Prog Cardiovasc Dis56, 382-390.

Bartness TJ, Shrestha YB, Vaughan CH, Schwartz GJ & Song CK. (2010). Sensory and sympathetic nervous system control of white adipose tissue lipolysis. Mol Cell

Endocrinol318, 34-43.

Bauduceau B, Vachey E, Mayaudon H, Burnat P, Dupuy O, Garcia C, Ceppa F & Bordier L. (2007). Should we have more definitions of metabolic syndrome or simply take waist measurement? Diabetes Metab33, 333-339.

Bayer M, Kuci Z, Schomig E, Grundemann D, Dittmann H, Handgretinger R & Bruchelt G. (2009). Uptake of mIBG and catecholamines in noradrenaline- and organic cation transporter-expressing cells: potential use of corticosterone for a preferred uptake in neuroblastoma- and pheochromocytoma cells. Nucl Med Biol36, 287-294.

Becker RL, Jr. (1993). Standardization and quality control of quantitative microscopy in pathology. J Cell Biochem Suppl17g, 199-204.

Benedict CR, Fillenz M & Stanford C. (1978). Changes in plasma noradrenaline concentration as a measure of release rate. Br J Pharmacol64, 305-309.

Bjorndal B, Burri L, Staalesen V, Skorve J & Berge RK. (2011). Different adipose depots: their role in the development of metabolic syndrome and mitochondrial response to hypolipidemic agents. J Obes2011, 490650.

Bjursell M, Ahnmark A, Bohlooly YM, William-Olsson L, Rhedin M, Peng XR, Ploj K, Gerdin AK, Arnerup G, Elmgren A, Berg AL, Oscarsson J & Linden D. (2007). Opposing effects of adiponectin receptors 1 and 2 on energy metabolism. Diabetes56, 583-593.

Bloom JD, Dutia MD, Johnson BD, Wissner A, Burns MG, Largis EE, Dolan JA & Claus TH. (1992). Disodium (R,R)-5-[2-[[2-(3-chlorophenyl)-2-hydroxyethyl]-amino] propyl]-1,3- benzodioxole-2,2-dicarboxylate (CL 316,243). A potent beta-adrenergic agonist virtually specific for beta 3 receptors. A promising antidiabetic and antiobesity agent. J Med Chem35, 3081-3084.

164 Bluher M, Bullen JW, Jr., Lee JH, Kralisch S, Fasshauer M, Kloting N, Niebauer J, Schon MR, Williams CJ & Mantzoros CS. (2006). Circulating adiponectin and expression of adiponectin receptors in human skeletal muscle: associations with metabolic parameters and insulin resistance and regulation by physical training. J Clin Endocrinol

Metab91, 2310-2316.

Bradley RL, Jeon JY, Liu FF & Maratos-Flier E. (2008). Voluntary exercise improves insulin sensitivity and adipose tissue inflammation in diet-induced obese mice. Am J Physiol

Endocrinol Metab295, E586-594.

Breese GR & Traylor TD. (1970). Effect of 6-hydroxydopamine on brain norepinephrine and dopamine evidence for selective degeneration of catecholamine neurons. J Pharmacol

Exp Ther174, 413-420.

Breese GR & Traylor TD. (1971). Depletion of brain noradrenaline and dopamine by 6- hydroxydopamine. Br J Pharmacol42, 88-99.

Brennan AM & Mantzoros CS. (2006). Drug Insight: the role of leptin in human physiology and pathophysiology--emerging clinical applications. Nat Clin Pract Endocrinol Metab 2,

318-327.

Briones AM, Daly CJ, Jimenez-Altayo F, Martinez-Revelles S, Gonzalez JM, McGrath JC & Vila E. (2005). Direct demonstration of beta1- and evidence against beta2- and beta3- adrenoceptors, in smooth muscle cells of rat small mesenteric arteries. Br J Pharmacol

146, 679-691.

British Heart Foundation. (2017). Your weight and heart disease. https://www.bhf.org.uk/heart- health/risk-factors/your-weight-and-heart-disease [accessed 04/01/17].

Brito NA, Brito MN & Bartness TJ. (2008). Differential sympathetic drive to adipose tissues after food deprivation, cold exposure or glucoprivation. Am J Physiol Regul Integr Comp

Physiol294, R1445-1452.

Brown EN, Lydic R & Schiff ND. (2010). General anesthesia, sleep, and coma. N Engl J Med

363, 2638-2650.

Bulloch JM & Daly CJ. (2014). Autonomic nerves and perivascular fat: interactive mechanisms.

Pharmacol Ther143, 61-73.

Bussey CE, Withers SB, Aldous RG, Edwards G & Heagerty AM. (2016). Obesity-Related Perivascular Adipose Tissue Damage Is Reversed by Sustained Weight Loss in the Rat. Arterioscler Thromb Vasc Biol36, 1377-1385.

Bylund DB, Eikenberg DC, Hieble JP, Langer SZ, Lefkowitz RJ, Minneman KP, Molinoff PB, Ruffolo RR, Jr. & Trendelenburg U. (1994). International Union of Pharmacology nomenclature of adrenoceptors. Pharmacol Rev46, 121-136.

Candelore MR, Deng L, Tota L, Guan XM, Amend A, Liu Y, Newbold R, Cascieri MA & Weber AE. (1999). Potent and selective human beta(3)-adrenergic receptor antagonists. J

165 Cannon B, Nedergaard J, Lundberg JM, Hokfelt T, Terenius L & Goldstein M. (1986). 'Neuropeptide tyrosine' (NPY) is co-stored with noradrenaline in vascular but not in parenchymal sympathetic nerves of brown adipose tissue. Exp Cell Res164, 546-550. Chamberlain PD, Jennings KH, Paul F, Cordell J, Berry A, Holmes SD, Park J, Chambers J,

Sennitt MV, Stock MJ, Cawthorne MA, Young PW & Murphy GJ. (1999). The tissue distribution of the human beta3-adrenoceptor studied using a monoclonal antibody: direct evidence of the beta3-adrenoceptor in human adipose tissue, atrium and skeletal muscle. Int J Obes Relat Metab Disord23, 1057-1065.

Chang S, Graham B, Yakubu F, Lin D, Peters JC & Hill JO. (1990). Metabolic differences between obesity-prone and obesity-resistant rats. Am J Physiol259, R1103-1110. Chaolu H, Asakawa A, Ushikai M, Li YX, Cheng KC, Li JB, Zoshiki T, Terashi M, Tanaka C,

Atsuchi K, Sakoguchi T, Tsai M, Amitani H, Horiuchi M, Takeuchi T & Inui A. (2011). Effect of exercise and high-fat diet on plasma adiponectin and nesfatin levels in mice.

Exp Ther Med2, 369-373.

Chen B, Lam KS, Wang Y, Wu D, Lam MC, Shen J, Wong L, Hoo RL, Zhang J & Xu A. (2006). Hypoxia dysregulates the production of adiponectin and plasminogen activator inhibitor- 1 independent of reactive oxygen species in adipocytes. Biochem Biophys Res

Commun341, 549-556.

Chrousos GP. (2000). The role of stress and the hypothalamic-pituitary-adrenal axis in the pathogenesis of the metabolic syndrome: neuro-endocrine and target tissue-related causes. Int J Obes Relat Metab Disord24 Suppl 2, S50-55.

Ciarimboli G & Schlatter E. (2005). Regulation of organic cation transport. Pflugers Arch 449,

423-441.

Civantos Calzada B & Aleixandre de Artinano A. (2001). Alpha-adrenoceptor subtypes.

Pharmacol Res44, 195-208.

Coelho M, Oliveira T & Fernandes R. (2013). Biochemistry of adipose tissue: an endocrine organ. Arch Med Sci9, 191-200.

Collins S, Daniel KW & Rohlfs EM. (1999). Depressed expression of adipocyte beta-adrenergic receptors is a common feature of congenital and diet-induced obesity in rodents. Int J

Obes Relat Metab Disord23, 669-677.

Correll JW. (1963). Adipose tissue: ability to respond to nerve stimulation in vitro. Science 140,

387-388.

Cousin B, Cinti S, Morroni M, Raimbault S, Ricquier D, Penicaud L & Casteilla L. (1992). Occurrence of brown adipocytes in rat white adipose tissue: molecular and morphological characterization. J Cell Sci103 ( Pt 4), 931-942.

D'Souza A, Bucchi A, Johnsen AB, Logantha SJ, Monfredi O, Yanni J, Prehar S, Hart G, Cartwright E, Wisloff U, Dobryznski H, DiFrancesco D, Morris GM & Boyett MR. (2014). Exercise training reduces resting heart rate via downregulation of the funny channel HCN4. Nat Commun5, 3775.

166 Dashwood MR, Dooley A, Shi-Wen X, Abraham DJ & Souza DS. (2007). Does periadventitial fat-derived nitric oxide play a role in improved saphenous vein graft patency in patients undergoing coronary artery bypass surgery? J Vasc Res44, 175-181.

Daugherty A, Rateri D, Hong L & Balakrishnan A. (2009). Measuring blood pressure in mice using volume pressure recording, a tail-cuff method. J Vis Exp.

de Boer MP, Meijer RI, Richter EA, van Nieuw Amerongen GP, Sipkema P, van Poelgeest EM, Aman J, Kokhuis TJ, Koolwijk P, van Hinsbergh VW, Smulders YM, Serne EH & Eringa EC. (2016). Globular adiponectin controls insulin-mediated vasoreactivity in muscle through AMPKalpha2. Vascul Pharmacol78, 24-35.

De Matteis R, Arch JR, Petroni ML, Ferrari D, Cinti S & Stock MJ. (2002). Immunohistochemical identification of the beta(3)-adrenoceptor in intact human adipocytes and ventricular myocardium: effect of obesity and treatment with ephedrine and caffeine. Int J Obes

Relat Metab Disord26, 1442-1450.

De Rosa A, Monaco ML, Capasso M, Forestieri P, Pilone V, Nardelli C, Buono P & Daniele A. (2013). Adiponectin oligomers as potential indicators of adipose tissue improvement in obese subjects. Eur J Endocrinol169, 37-43.

Demerath EW, Sun SS, Rogers N, Lee M, Reed D, Choh AC, Couch W, Czerwinski SA, Chumlea WC, Siervogel RM & Towne B. (2007). Anatomical patterning of visceral adipose tissue: race, sex, and age variation. Obesity (Silver Spring)15, 2984-2993. Deng C, Paoloni-Giacobino A, Kuehne F, Boss O, Revelli JP, Moinat M, Cawthorne MA, Muzzin

P & Giacobino JP. (1996). Respective degree of expression of beta 1-, beta 2- and beta 3-adrenoceptors in human brown and white adipose tissues. Br J Pharmacol118, 929- 934.

Dessy C & Balligand JL. (2010). Beta3-adrenergic receptors in cardiac and vascular tissues emerging concepts and therapeutic perspectives. Adv Pharmacol59, 135-163.

Ding C, Guo J & Su Z. (2015). The status of research into resistance to diet-induced obesity.

Horm Metab Res47, 404-410.

Ding M, Carrao AC, Wagner RJ, Xie Y, Jin Y, Rzucidlo EM, Yu J, Li W, Tellides G, Hwa J, Aprahamian TR & Martin KA. (2012). Vascular smooth muscle cell-derived adiponectin: a paracrine regulator of contractile phenotype. J Mol Cell Cardiol52, 474-484.

Ding M, Xie Y, Wagner RJ, Jin Y, Carrao AC, Liu LS, Guzman AK, Powell RJ, Hwa J, Rzucidlo EM & Martin KA. (2011). Adiponectin induces vascular smooth muscle cell differentiation via repression of mammalian target of rapamycin complex 1 and FoxO4.

Arterioscler Thromb Vasc Biol31, 1403-1410.

Dixon RA, Kobilka BK, Strader DJ, Benovic JL, Dohlman HG, Frielle T, Bolanowski MA, Bennett CD, Rands E, Diehl RE, Mumford RA, Slater EE, Sigal IS, Caron MG, Lefkowitz RJ & Strader CD. (1986). Cloning of the gene and cDNA for mammalian beta-adrenergic receptor and homology with rhodopsin. Nature321, 75-79.

167 Dunbar JC, Hu Y & Lu H. (1997). Intracerebroventricular leptin increases lumbar and renal sympathetic nerve activity and blood pressure in normal rats. Diabetes46, 2040-2043. Duriancik DM & Hoag KA. (2010). Vitamin A deficiency alters splenic dendritic cell subsets and

increases CD8(+)Gr-1(+) memory T lymphocytes in C57BL/6J mice. Cell Immunol265,

156-163.

Edwards G, Feletou M & Weston AH. (2010). Endothelium-derived hyperpolarising factors and associated pathways: a synopsis. Pflugers Arch459, 863-879.

Egawa M, Yoshimatsu H & Bray GA. (1989). Effects of 2-deoxy-D-glucose on sympathetic nerve activity to interscapular brown adipose tissue. Am J Physiol257, R1377-1385. Elgar M. (1992). Cannibalism: Ecology and Evolution Among Diverse Taxa. Oxford University

Press, Social Science.

Enzo Life Sciences. (2017). Blocking petide for adiponectin rectpor 1. http://www.enzolifesciences.com/ALX-151-045/blocking-peptide-for-adiponectin-

receptor-1-pab-prod.-no.-alx-210-645/ [accessed 12/12/17].

Eringa EC, Bakker W, Smulders YM, Serne EH, Yudkin JS & Stehouwer CD. (2007). Regulation of vascular function and insulin sensitivity by adipose tissue: focus on perivascular adipose tissue. Microcirculation14, 389-402.

Evans BA, Papaioannou M, Hamilton S & Summers RJ. (1999). Alternative splicing generates two isoforms of the beta3-adrenoceptor which are differentially expressed in mouse tissues. Br J Pharmacol127, 1525-1531.

Fabbiano S, Suarez-Zamorano N, Rigo D, Veyrat-Durebex C, Stevanovic Dokic A, Colin DJ & Trajkovski M. (2016). Caloric Restriction Leads to Browning of White Adipose Tissue through Type 2 Immune Signaling. Cell Metab24, 434-446.

Feng M, Whitesall S, Zhang Y, Beibel M, D'Alecy L & DiPetrillo K. (2008). Validation of volume- pressure recording tail-cuff blood pressure measurements. Am J Hypertens 21, 1288- 1291.

Fesus G, Dubrovska G, Gorzelniak K, Kluge R, Huang Y, Luft FC & Gollasch M. (2007). Adiponectin is a novel humoral vasodilator. Cardiovasc Res75, 719-727.

Florian JP & Pawelczyk JA. (2010). Non-esterified fatty acids increase arterial pressure via central sympathetic activation in humans. Clin Sci (Lond)118, 61-69.

Foller M, Jaumann M, Dettling J, Saxena A, Pakladok T, Munoz C, Ruth P, Sopjani M, Seebohm G, Ruttiger L, Knipper M & Lang F. (2012). AMP-activated protein kinase in BK-channel regulation and protection against hearing loss following acoustic overstimulation. Faseb j26, 4243-4253.

Foster MT & Bartness TJ. (2006). Sympathetic but not sensory denervation stimulates white adipocyte proliferation. Am J Physiol Regul Integr Comp Physiol291, R1630-1637.

168 Frielle T, Collins S, Daniel KW, Caron MG, Lefkowitz RJ & Kobilka BK. (1987). Cloning of the cDNA for the human beta 1-adrenergic receptor. Proc Natl Acad Sci U S A 84, 7920- 7924.

Fuente-Martin E, Argente-Arizon P, Ros P, Argente J & Chowen JA. (2013). Sex differences in adipose tissue: It is not only a question of quantity and distribution. Adipocyte 2, 128- 134.

Fukao M, Mason HS, Britton FC, Kenyon JL, Horowitz B & Keef KD. (1999). Cyclic GMP- dependent protein kinase activates cloned BKCa channels expressed in mammalian cells by direct phosphorylation at serine 1072. J Biol Chem274, 10927-10935.

Furlan C, Sterin-Borda L & Borda E. (2005). Activation of beta3 adrenergic receptor decreases DNA synthesis in human skin fibroblasts via cyclic GMP/nitric oxide pathway. Cell

Physiol Biochem16, 175-182.

Galvez-Prieto B, Dubrovska G, Cano MV, Delgado M, Aranguez I, Gonzalez MC, Ruiz-Gayo M, Gollasch M & Fernandez-Alfonso MS. (2008). A reduction in the amount and anti- contractile effect of periadventitial mesenteric adipose tissue precedes hypertension development in spontaneously hypertensive rats. Hypertens Res31, 1415-1423. Galvez-Prieto B, Somoza B, Gil-Ortega M, Garcia-Prieto CF, de Las Heras AI, Gonzalez MC,

Arribas S, Aranguez I, Bolbrinker J, Kreutz R, Ruiz-Gayo M & Fernandez-Alfonso MS. (2012). Anticontractile Effect of Perivascular Adipose Tissue and Leptin are Reduced in Hypertension. Front Pharmacol3, 103.

Gao Y. (2010). The multiple actions of NO. Pflugers Arch459, 829-839.

Gao YJ, Lu C, Su LY, Sharma AM & Lee RM. (2007). Modulation of vascular function by perivascular adipose tissue: the role of endothelium and hydrogen peroxide. Br J

Pharmacol151, 323-331.

Gao YJ, Takemori K, Su LY, An WS, Lu C, Sharma AM & Lee RM. (2006). Perivascular adipose tissue promotes vasoconstriction: the role of superoxide anion. Cardiovasc Res 71,

363-373.

Garekani ET, Mohebbi H, Kraemer RR & Fathi R. (2011). Exercise training intensity/volume affects plasma and tissue adiponectin concentrations in the male rat. Peptides 32,

1008-1012.

Gasser PJ, Orchinik M, Raju I & Lowry CA. (2009). Distribution of organic cation transporter 3, a corticosterone-sensitive monoamine transporter, in the rat brain. J Comp Neurol 512,

529-555.

Gauthier C, Langin D & Balligand JL. (2000). Beta3-adrenoceptors in the cardiovascular system. Trends Pharmacol Sci21, 426-431.

Gauthier C, Leblais V, Kobzik L, Trochu JN, Khandoudi N, Bril A, Balligand JL & Le Marec H. (1998). The negative inotropic effect of beta3-adrenoceptor stimulation is mediated by activation of a nitric oxide synthase pathway in human ventricle. J Clin Invest 102,

169 Giordano A, Song CK, Bowers RR, Ehlen JC, Frontini A, Cinti S & Bartness TJ. (2006). White adipose tissue lacks significant vagal innervation and immunohistochemical evidence of parasympathetic innervation. In Am J Physiol Regul Integr Comp Physiol, pp. R1243- 1255. United States.

Gollasch M. (2012). Vasodilator signals from perivascular adipose tissue. Br J Pharmacol165,

633-642.

Gorboulev V, Ulzheimer JC, Akhoundova A, Ulzheimer-Teuber I, Karbach U, Quester S, Baumann C, Lang F, Busch AE & Koepsell H. (1997). Cloning and characterization of two human polyspecific organic cation transporters. DNA Cell Biol16, 871-881.

Granneman JG, Lahners KN & Chaudhry A. (1991). Molecular cloning and expression of the rat beta 3-adrenergic receptor. Mol Pharmacol40, 895-899.

Grassi G, Seravalle G & Dell'oro R. (2010). Sympathetic activation in obesity: a noninnocent bystander. In Hypertension, pp. 338-340. United States.

Gray SL & Vidal-Puig AJ. (2007). Adipose tissue expandability in the maintenance of metabolic homeostasis. Nutr Rev65, S7-12.

Greenstein AS, Khavandi K, Withers SB, Sonoyama K, Clancy O, Jeziorska M, Laing I, Yates AP, Pemberton PW, Malik RA & Heagerty AM. (2009). Local inflammation and hypoxia abolish the protective anticontractile properties of perivascular fat in obese patients.

Circulation119, 1661-1670.

Griffith J & Farris E. (1942). The rat in laboratory investigation. J B Lipincott Company, London.