Scientific Online Resource System

Adipobiology

Are adipocytes and ROS villains, or are they protagonists in the drama of life? The murburn perspective

Vivian David Jacob, Kelath Murali Manoj

Abstract

Several questions remain unanswered regarding the roles and interactive dynamics of reactive oxygen species (ROS) and lipids/adipocytes. ROS have been conventionally associated with deleterious effects in biological systems, especially correlated with metabolic disorders exemplified by diabetes, obesity, cancer, atherogenesis, etc. Adipocytes, originally perceived as mere lipid-storing cells, were also associated with such metabolic disorders. In later times, adipose tissue was shown to have several favorable metabolic and physiological functions. Similarly, ROS were also acknowledged with favorable roles in cellular signaling. Very recently, ROS have been shown to be indispensable protagonists of key life-sustaining routines such as oxidative phosphorylation, thermogenesis and xenobiotics’ metabolism. In the light of these developments, herein, we attempt to address why different research groups derive data that project/infer contrasting correlations of ROS and lipids with good health. We advocate that rather than seeing ROS and fat deposition as deleterious to health, the modality of their generation, loci of presence and the relative amounts/distribution in milieu are the crucial factors that determine their interactions/roles (and thereby, the resulting physiology!) in miscellaneous microenvironments.

Full Text


References

Valko M, Leibfritz D, Moncol J, Cronin MTD, Mazur M, Telser J. Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol 2007; 39: 44-84. doi:10.1016/j.biocel.2006.07.001.

Willcox JK, Ash SL, Catignani GL. Antioxidants and prevention of chronic disease. Rev Crit Rev Food Sci Nutr 2004; 44: 275–295. doi: 10.1080/10408690490468489.

Parthasarathy S, N Santanam, S Ramachandran, O Meilhac. Oxidants and antioxidants in atherogenesis: an appraisal. J Lipid Res 1999; 40: 2143–2157. doi:10.1002/jcc.20084.

Halliwell B, Gutteridge JMC. Free Radicals in Biology and Medicine. Clarendon Press, 2007. DOI: 10.1002/jcc.20084.

Droge W. Free radicals in the physiological control of cell function. Physiol Rev 2002; 82: 47–95. DOI: 10.1152/physrev.00018.2001.

Dizdaroglu M, Jaruga P, Birincioglu M, Rodriguez H. Free radical-induced damage to DNA: mechanisms and measurement. Free Radic Biol Med 2002; 32: 1102-1115. doi:10.1016/S0891-5849(02)00826-2

Hofer T, Badouard C, Bajak E, Ravanat JL, Mattsson A, Cotgreave IA. Hydrogen peroxide causes greater oxidation in cellular RNA than in DNA. Biol Chem 2005; 386: 333- 337. doi: 10.1515/BC.2005.040.

Negre-Salvayre A, Coatrieux C, Ingueneau C, Salvayre R. Advanced lipid peroxidation end products in oxidative damage to proteins. Potential role in diseases and therapeutic prospects for the inhibitors. Br J Pharmacol 2008; 153: 6-20. doi:10.1038/sj.bjp.0707395.

Yin H, Xu L, Porter NA. Free Radical Lipid Peroxidation: Mechanisms and Analysis. Chem Rev 2011; 111: 5944- 5972. doi:10.1021/cr200084z.

Dean RT, Fu S, Stocker R, Davies MJ. Biochemistry and pathology of radical-mediated protein oxidation. Biochem J 1997; 324: 1-18. doi:10.1042/bj3240001.

Butterfield DA, Koppal T, Howard B, et al. Structur- al and functional changes in proteins induced by free radical-mediated oxidative stress and protective action of the antioxidants N-tert-butyl-alpha-phenylnitrone and vitamin E. Ann NY Acad Sci 1998; 854: 448-462. doi:10.1111/j.1749-6632.1998.tb09924.x.

Ignarro LJ, Buga GM, Wood KS, Byrns RE, Chaudhuri G. Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide. Proc Natl Acad Sci U S A 1987; 84: 9265-9269. doi:10.1073/ pnas.84.24.9265.

D’Autréaux B, Toledano MB. ROS as signalling molecules: mechanisms that generate specificity in ROS homeostasis. Nat Rev Mol Cell Biol 2007; 8: 813. DOI: 10.1038/nrm2256.

Wu W.S. The signalling mechanism of ROS in tumor progression. Cancer Metastasis Rev 2006; 25: 695–705. doi: 10.1007/s10555-006-9037-8.

Zhang J, Wang X, Vikash V, et al. ROS and ROS-Mediat- ed Cellular Signaling. Oxid Med Cell Longev 2016; 2016: 4350965. doi:10.1155/2016/4350965.

Schieber M, Chandel NS. ROS function in redox signaling and oxidative stress. Curr Biol 2014; 24: R453-62. DOI: 10.1016/j.cub.2014.03.034.

Howlett R. Nobel award stirs up debate on nitric oxide breakthrough. Nature. 1998; 395: 625. https://doi. org/10.1038/27019.

Rosen ED, Spiegelman BM. Adipocytes as regulators of energy balance and glucose homeostasis. Nature 2006; 444: 847-853. doi:10.1038/nature05483.

Cannon B, Nedergaard J. Brown adipose tissue: function and physiological significance. Physiol Rev 2004; 84: 277- 359. doi:10.1152/physrev.00015.2003.

Giralt M, Villarroya F. White, brown, beige/brite: different adipose cells for different functions? Endocrinology 2013; 154: 2992-3000. doi:10.1210/en.2013-1403.

Casteilla L, Penicaud L, Cousin B, Calise D. Choosing an adipose tissue depot for sampling: factors in selection and depot specificity. Methods Mol Biol 2008; 456: 23-38. doi:10.1007/978-1-59745-245-8_2.

Kawamura K, Qi F, Kobayashi J. Potential relationship be- tween the biological effects of low-dose irradiation and mitochondrial ROS production. J Radiat Res 2018; 59: ii91- ii97. http://dx.doi.org/10.1093/jrr/rrx091.

Yamamori T, Yasui H, Yamazumi M, et al. Ionizing radiation induces mitochondrial reactive oxygen species production accompanied by upregulation of mitochondrial electron transport chain function and mitochondrial content under control of the cell cycle checkpoint. Free Radic Biol Med. 2012; 53: 260-270. doi:10.1016/j.freeradbiomed.2012.04.033.

Manoj KM. Chlorinations catalyzed by chloroperoxidase occur via diffusible intermediate(s) and the reaction components play multiple roles in the overall process. Biochim Biophys Acta 2006; 1764: 1325-1339. doi:10.1016/j.bbapap.2006.05.012.

Manoj KM, Hager LP. Chloroperoxidase, a janus enzyme. Biochemistry 2008; 47: 2997-3003. doi:10.1021/ bi7022656.

Manoj KM, Baburaj A, Ephraim B, et al. Explaining the atypical reaction profiles of heme enzymes with a novel mechanistic hypothesis and kinetic treatment. PLoS One 2010; 5: e10601. doi:10.1371/journal.pone.0010601.

Manoj KM, Gade SK, Mathew L. Cytochrome P450 reductase: a harbinger of diffusible reduced oxygen species. PLoS One 2010; 5: e13272. doi:10.1371/journal.pone.0013272.

Andrew D, Hager L, Manoj KM. The intriguing enhancement of chloroperoxidase mediated one-electron oxidations by azide, a known active-site ligand. Biochem Biophys Res Commun 2011; 415: 646-649. doi:10.1016/j. bbrc.2011.10.128.

Gade SK, Bhattacharya S, Manoj KM. Redox active molecules cytochrome c and vitamin C enhance heme-enzyme peroxidations by serving as non-specific agents for redox relay. Biochem Biophys Res Commun 2012; 419: 211-214. doi:10.1016/j.bbrc.2012.01.149.

Parashar A, Manoj KM. Traces of certain drug molecules can enhance heme-enzyme catalytic outcomes. Biochem Biophys Res Commun 2012; 417: 1041-1045. doi:10.1016/j. bbrc.2011.12.090.

Gideon DA, Kumari R, Lynn AM, Manoj KM. What is the functional role of N-terminal transmembrane helices in the metabolism mediated by liver microsomal cytochrome P450 and its reductase? Cell Biochem Biophys 2012; 63: 35– 45. doi:10.1007/s12013-012-9339-0.

Parashar A, Gade SK, Potnuru M, Madhavan N, Manoj KM. The curious case of benzbromarone: insight into super-inhibition of cytochrome P450. PLoS One 2014; 9: e89967. doi:10.1371/journal.pone.0089967.

Parashar A, Venkatachalam A, Gideon DA, Manoj KM. Cyanide does more to inhibit heme enzymes, than merely serving as an active-site ligand. Biochem Biophys Res Com­ mun 2014; 455: 190-193. doi:10.1016/j.bbrc.2014.10.137.

Manoj KM, Gade SK, Venkatachalam A, Gideon DA. Electron transfer amongst flavo- and hemo-proteins: dif- fusible species effect the relay processes, not protein–protein binding. RSC Adv 2016; 6: 24121-24129. doi:10.1039/ C5RA26122H.

Manoj KM, Parashar A, Venkatachalam A, et al. Atypical profiles and modulations of heme-enzymes catalyzed outcomes by low amounts of diverse additives suggest diffusible radicals’ obligatory involvement in such redox reactions. Biochimie 2016; 125: 91-111. doi:10.1016/j.biochi.2016.03.003.

Manoj KM, Parashar A, Gade SK, Venkatachalam A. Functioning of microsomal cytochrome P450s: Murburn concept explains the metabolism of xenobiotics in hepatocytes. Front Pharmacol 2016; 7: 161. doi:10.3389/ fphar.2016.00161.

Manoj KM, Venkatachalam A, Parashar A. Metabolism of xenobiotics by cytochrome P450: novel insights into the thermodynamics, kinetics and roles of redox proteins and diffusible reactive species. Drug Metab Rev 2016; 48: 41-42. doi:10.1080/03602532.2016.1191848.

Venkatachalam A, Parashar A, Manoj KM. Functioning of drug-metabolizing microsomal cytochrome P450s: In silico probing of proteins suggests that the distal heme “active site” pocket plays a relatively “passive role” in some enzyme-substrate interactions. In silico Pharmacol 2016; 4: 2. doi:10.1186/s40203-016-0016-7.

Manoj KM. Debunking chemiosmosis and proposing murburn concept as the explanation for cellular respiration. Biomed Rev 2017; 28: 35-52. doi:10.14748/bmr.v28.4450.

Manoj KM. Aerobic respiration: Criticism of the proton-centric explanation involving rotary ATP synthesis, chemiosmosis principle, proton pumps and electron transport chain. Biochem Insi 2018. doi: 10.1177/1178626418818442.

Manoj KM, Parashar A, Jacob VD, Ramasamy S. Aerobic respiration: Proof of concept for the murburn perspective. 2018. doi: 10.1080/07391102.2018.1552896.

Manoj KM. Murburn scheme for thermogenesis mediated by uncoupling protein. 2018. arXiv:1812.06089 [q-bio.SC]

Parashar A, Gideon DA, Manoj KM. Murburn Concept: A molecular explanation for hormetic and idiosyncratic dose responses. Dose Response 2018; 16: 1559325818774421. doi:10.1177/1559325818774421.

Watson JD. Type 2 diabetes as a redox disease. Lancet 2014; 383: 841-843. doi:10.1016/S0140-6736(13)62365-X.

Mittler R. ROS Are Good. Trends Plant Sci 2017; 22: 11-19. doi:10.1016/j.tplants.2016.08.002.

Huo Y, Qiu W-Y, Pan Q, Yao Y-F, Xing K, Lou MF. Reactive oxygen species (ROS) are essential mediators in epidermal growth factor (EGF)-stimulated corneal epithelial cell proliferation, adhesion, migration, and wound healing. Exp Eye Res 2009; 89: 876-886. doi:10.1016/j. exer.2009.07.012.

Bray GA, Bellanger T. Epidemiology, trends, and morbidities of obesity and the metabolic syndrome. Endocrine 2006; 29: 109-117. doi:10.1385/ENDO:29:1:109.

Chaldakov GN, Stankulov IS, Aloe L. Subepicardial adipose tissue in human coronary atherosclerosis: another neglected phenomenon. Atherosclerosis 2001; 154: 237–238. doi:10.1016/S0021-9150(00)00676-6.

Trayhurn P. Endocrine and signalling role of adipose tissue: new perspectives on fat. Acta Physiol Scand 2005; 184: 285- 293. doi:10.1111/j.1365-201X.2005.01468.x.

Sethi JK, Vidal-Puig AJ. Thematic review series: adipocyte biology. Adipose tissue function and plasticity orchestrate nutritional adaptation. J Lipid Res 2007; 48: 1253-1262. doi:10.1194/jlr.R700005-JLR200.

Besnard P, Passilly-Degrace P, Khan NA. Taste of fat: A sixth taste modality? Physiol Rev 2016; 96: 151-176. doi:10.1152/ physrev.00002.2015.

Chaldakov GN, Fiore M, Tonchev AB, Aloe L. Adipopharmacology, a novel drug discovery approach: A metabotrophic perspective. Lett Drug Des Discov 2006; 3: 503-505. doi:http://dx.doi.org/10.2174/157018006778194835.

Vistoli G, De Maddis D, Cipak A, Zarkovic N, Carini M, Aldini G. Advanced glycoxidation and lipoxidation end products (AGEs and ALEs): an overview of their mechanisms of formation. Free Radic Res. 2013; 47: 3-27. doi:10.3 109/10715762.2013.815348.

Steinberg D. Low density lipoprotein oxidation and its pathobiological significance. J Biol Chem 1997; 272: 20963– 20966. 10.1016/S0006-3495(93)81518-2.

Palinski W, Rosenfeld ME, Yla-Herttuala S, Gurtner GC, Socher SS, Butler SW, et al. Low density lipoprotein undergoes oxidative modification in vivo. Proc Natl Acad Sci USA 1989; 86: 1372–1376. doi:10.1073/pnas.86.4.1372.

Fredrikson GN, Berglund G, Alm R, Nilsson JA, Shah PK, Nilsson J. Identification of autoantibodies in human plasma recognizing an apoB-100 LDL receptor binding site peptide. J Lipid Res 2006; 47: 2049–2054. doi: 10.1194/jlr. M600217-JLR200.

Siems W, Quast S, Carluccio F, Wiswedel I, Hirsch D, Augustin W, et al. Oxidative stress in chronic renal failure as a cardiovascular risk factor. Clin Nephrol 2002; 58: S12– S19.

Carluccio F, Siems W, Stefanelli G, Sommerburg O, Grune T, Riedel E, et al. Homocysteine in chronic renal failure in relation to renal anemia and to oxidative stress parameters 4-hydroxynonenal and malondialdehyde. Clin Nephrol 2002; 58: S26–S30.

Yoritaka A, Hattori N, Uchida K, Tanaka M, Stadtman ER, Mizuno Y. Immunohistochemical detection of 4-hydroxynonenal protein adducts in Parkinson disease. Proc Natl Acad Sci USA 1996; 93: 2696–2701.

Jenner P. Oxidative stress in Parkinson’s disease. Ann Neurol 2003; 53:S26-36; S36-38. doi:10.1002/ana.10483.

Pierre F, Peiro G, Tache S, Cross AJ, Bingham SA, Gasc N, et al. New marker of colon cancer risk associated with heme intake: 1,4-dihydroxynonane mercapturic acid. Cancer Epidemiol Biomarkers Prev 2006; 15: 2274–2279. doi: 10.1158/1055-9965.EPI-06-0085.

Pierre F, Tache S, Gueraud F, Rerole AL, Jourdan ML, Petit C. Apc mutation induces resistance of colonic cells to lipoperoxide-triggered apoptosis induced by faecal water from haem-fed rats. Carcinogenesis 2007; 28: 321–327. doi: 10.1093/carcin/bgl127.

Weber LW, Boll M, Stampfl A. Hepatotoxicity and mechanism of action of haloalkanes: carbon tetrachloride as a toxicological model. Crit Rev Toxicol 2003; 33: 105–136. doi: 10.1080/713611034.

Grune T, Michel P, Sitte N, Eggert W, Albrecht-Nebe H, Esterbauer H, et al. Increased levels of 4-hydroxynonenal modified proteins in plasma of children with autoimmune diseases. Free Radic Biol Med 1997; 23: 357–360. doi:10.1016/S0891-5849(96)00586-2.

Boldogh I, Bacsi A, Choudhury BK, Dharajiya N, Alam R, Hazra TK, et al. ROS generated by pollen NADPH oxidase provide a signal that augments antigen-induced allergic airway inflammation. J Clin Invest 2005; 115: 2169–2179. doi: 10.1172/JCI24422.

Almolki A, Taille C, Martin GF, Jose PJ, Zedda C, Conti M, et al. Heme oxygenase attenuates allergen-induced airway inflammation and hyperreactivity in guinea pigs. Am J Physiol Lung Cell Mol Physiol 2004; 287: L26–L34. doi: 10.1152/ajplung.00237.2003.

Skorokhod OA, Caione L, Marrocco T, et al. Inhibition of erythropoiesis in malaria anemia: role of hemozoin and hemozoin-generated 4-hydroxynonenal. Blood 2010; 116: 4328-4337. doi:10.1182/blood-2010-03-272781.

Albright CD, Klem E, Shah AA, Gallagher P. Breast cancer cell-targeted oxidative stress: enhancement of cancer cell uptake of conjugated linoleic acid, activation of p53, and inhibition of proliferation. Exp Mol Pathol 2005; 79: 118- 125. doi:10.1016/j.yexmp.2005.05.005.

Sunjic SB, Cipak A, Rabuzin F, Wildburger R, Zarkovic N. The influence of 4-hydroxy-2-nonenal on proliferation, differentiation and apoptosis of human osteosarcoma cells. Biofactors 2005; 24: 141-148. doi:10.1002/biof.5520240117.

Cerbone A, Toaldo C, Laurora S, et al. 4-Hydroxynonenal and PPARgamma ligands affect proliferation, differentiation, and apoptosis in colon cancer cells. Free Radic Biol Med 2007; 42: 1661-1670. doi:10.1016/j.freeradbiomed.2007.02.009.

Pizzimenti S, Menegatti E, Berardi D, et al. 4-hydroxynonenal, a lipid peroxidation product of dietary polyunsaturated fatty acids, has anticarcinogenic properties in colon carcinoma cell lines through the inhibition of telomerase activity. J Nutr Biochem 2010; 21: 818-826. doi:10.1016/j. jnutbio.2009.06.005.

Ayala A, Munoz MF, Arguelles S. Lipid peroxidation: production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal. Oxid Med Cell Longev 2014; 2014: 360438. doi:10.1155/2014/360438.

Cai H, Harrison DG. Endothelial dysfunction in cardiovas- cular diseases: the role of oxidant stress. Circ Res. 2000; 87: 840-844.

Bahorun T, Soobrattee MA, Luximon-Ramma V, Aruoma OI. Free radicals and antioxidants in cardiovascular health and disease. Internet J. Med. Update 2006; 1: 1–17. doi:10.4314/ijmu.v1i2.39839.

Schürmann C, Rezende F, Kruse C, et al. The NADPH oxidase Nox4 has anti-atherosclerotic functions. Eur Heart J 2015; 36: 3447-56. doi: 10.1093/eurheartj/ehv460.

Le Lay S, Simard G, Martinez MC, Andriantsitohaina R. Oxidative stress and metabolic pathologies: from an adipocentric point of view. Oxid Med Cell Longev 2014; 2014: 908539. doi:10.1155/2014/908539.

Furukawa S, Fujita T, Shimabukuro M, et al. Increased oxidative stress in obesity and its impact on metabolic syndrome. J Clin Invest 2004; 114: 1752-1761. doi:10.1172/ JCI21625.

Curtis JM, Grimsrud PA, Wright WS, et al. Downregulation of adipose glutathione S-transferase A4 leads to increased protein carbonylation, oxidative stress, and mitochondrial dysfunction. Diabetes 2010; 59: 1132-1142. doi:10.2337/ db09-1105.

31. Lin Y, Berg AH, Iyengar P, et al. The hyperglycemia-induced inflammatory response in adipocytes: the role of reactive oxygen species. J Biol Chem 2005; 280: 4617-4626. doi:10.1074/jbc.M411863200.

Cordeiro RM. Reactive oxygen species at phospholipid bilayers: Distribution, mobility and permeation. Biochim Biophys Acta ­ Biomembr 2014; 1838: 438-444. doi:10.1016/j. bbamem.2013.09.016.

Han CY. Roles of reactive oxygen species on insulin resistance in adipose tissue. Diabetes Metab J 2016; 40: 272-279. doi:10.4093/dmj.2016.40.4.272.

Nott TJ, Petsalaki E, Farber P, et al. Phase transition of a disordered nuage protein generates environmentally responsive membraneless organelles. Mol Cell 2015; 57: 936-947. doi:10.1016/j.molcel.2015.01.013.

Nott TJ, Craggs TD, Baldwin AJ. Membraneless organelles can melt nucleic acid duplexes and act as biomolecular filters. Nat Chem 2016; 8: 569-575. doi:10.1038/nchem.2519.

Feric M, Vaidya N, Harmon TS, et al. Coexisting liquid phases underlie nucleolar subcompartments. Cell 2016; 165: 1686-1697. doi:10.1016/j.cell.2016.04.047.

Wheeler JR, Matheny T, Jain S, Abrisch R, Parker R. Distinct stages in stress granule assembly and disassembly. Elife 2016; 5. doi:10.7554/eLife.18413.




DOI: http://dx.doi.org/10.14748/adipo.v10.6534

Refbacks

Article Tools
Email this article (Login required)
About The Authors

Vivian David Jacob
Satyamjayatu: The Science & Ethics Foundation, Kulappully, Shoranur-2 (PO), Palakkad District, Kerala, India
India

Kelath Murali Manoj
Satyamjayatu: The Science & Ethics Foundation, Kulappully, Shoranur-2 (PO), Palakkad District, Kerala, India
India

Font Size


|