Inflammatory Mechanisms in Obesity: what is known in cats?
Keywords:
Inflammation, Cytokines, Adpocytes, Immune responsesAbstract
This study aimed to provide an overview of the inflammatory mechanisms involved in the obesity process focusing on pro-inflammatory immune responses and the role of adipokines in inflammatory reactionsm in animals and humans, as well as the correlation with the feline specie. Obesity is considered an increasingly prevalent endocrine disease in feline species, caused by a nutritional disorder with negative energy balance. It is defined as an excessive accumulation of adipose tissue that negatively affects the animal's health and is associated with a decrease in life expectancy and as triggering causes are multifactorial, being linked to several genetic and environmental factors. Adipose tissue is an endocrine organ that actively participates in energy metabolism and concentrates hormonal factors that are secreted by adipocytes, which modulate metabolism and exert the ability to directly involve innate and adaptive immune responses through the activity of the main cell types, including adipocytes and macrophages responsible for the activation and release of cytokines that affect normal physiological function, influencing the development of chronic inflammation. The altered production of adipokines in obesity has been implicated in the pathophysiology of several groups of diseases and their possible contribution to the development of insulin resistance and diabetes mellitus. Despite the incomplete understanding of the triggering factors of inflammation in the adipose tissue of cats, it is suggested that aspects associated with mitochondrial dysfunction, hypoxia, or even intrinsic factors of the adipocyte are involved.
References
AHMED, B.; SULTANA, R.; GREENE, M.W. Adipose tissue and insulin resistance in obese. Biomedicine & Pharmacotherapy, v.137, n.1, p.1-13, 2021.
APPLETON, D.J.; RAND, J.S.; SUNVOLD, G.D. Plasma leptin concentrations in cats: Reference range, effect of weight gain and relationship with adiposity as measured by dual energy x-ray absorptiometry. Journal of Feline Medicine and Surgery, v.2, n.4, p.191-199, 2000.
ARMSTRONG, P.J.; LUSBY, A.L. Clinical importance of canine and feline obesity. In: TOWELL, T.L. Practical Weight Management in Dogs and Cats. 1a ed., New Jersey: Wiley-Blackwell, p.3-21, 2011.
BAKERS, R.G.; HAYDEN, M.S.; GHOSH, S. NF-KB Inflammation and metabolic disease. Cell Metabolism, v.13, n.1, p.11-22, 2011.
BARTON, G.M. A calculated response: control of inflammation by the innate immune system. Journal of Clinical Investigation, v.118, n.2, p.413–420, 2008.
BJORNVAD, C.; HOELMKJAER, K.M. Management of obesity in cats. Veterinary Medicine: Research and Reports, v.97, n.1, p.97-107, 2014.
BLÜHER, M. Importance of adipokines in glucose homeostasis. Diabetes Management journal, v.3, n.5, p.389–400, 2013.
BLÜHER, M.; MANTZOROS, C.S. From leptin to other adipokines in health and disease: facts and expectations at the beginning of the 21st Century. Metabolism, v.64, n.1, p.131-145, 2015.
CAO, H. Adipocytokines in obesity and metabolic disease. The Journal of Endocrinology, v.220, n.2, p.47-59, 2014.
CLARK, M.; HOENIG, M. Metabolic effects of obesity and its interaction with endocrine diseases. Veterinary Clinics of North America: Small Animal Practice, v.46, n.5, p.797-815, 2016.
CONDE, J.; SCOTECE, M.; GÓMEZ, R.; GÓMEZ-REINO, J.J.; LAGO, F.; GUALILLO, O. At the crossroad between immunity and metabolism: Focus on leptin. Expert Review of Clinical Immunology, v.6, n.5, p.801-808, 2010.
CORTESE, L.; TERRAZZANO, G.; PELAGALLI, A. Leptin and immunological profile in obesity and its associated diseases in dogs. International Journal of Molecular Science, v.20, n.10, p.2392-2411, 2019.
DE SOUZA, C.T.; ARAUJO, E.P.; BORDIN, S.; ASHIMINE, R.; ZOLLNER, R.L.; BOSCHERO, A.C.; SAAD, M.J.A.; VELLOSO, L.A. Consumption of a fat-rich diet activates a proinflammatory response and induces insulin resistance in the hypothalamus. Endocrinology, v.146, n.10, p.4192-4199, 2005.
DIB, L.H.; ORTEGA, M.T.; FLEMING, S.D.; CHAPES, S.K.; MELGAREJO, T. Bone marrow leptin signaling mediates obesity-associated adipose tissue inflammation in male mice. Endocrinology, v.155, n.1, p.40-46, 2014.
FARNIER, C.; KRIEF, S.; BLACHE, M.; DIOT-DUPUY, F.; MORY, G.; FERRE, P.; BAZIN R. Adipocyte functions are modulated by cell size change: potential involvement of an integrin/ERK signalling pathway. International Journal of Obesity and Related Metabolic Disorders, v.27, n.10, p.1178-1186, 2003.
FISCHER-POSOVASZKY, P.; WABISTSCH, M.; HOCHBERG, Z. Endocrinology of adipose tissue- an update. Hormone and Metabolic Research, v.39, n.5, p.314-321, 2007.
FORBES, J.M.; COOPER, M.E. Mechanisms of diabetic complications. Physiological Reviews, v.93, n.1, p.137-188, 2013.
GARAULET, M.; HERNANDEZ-MORANTE, J.J.; DE HEREDIA, F.P.; TÉBAR, J.B. Adiponectin, the controversial hormone. Public Health Nutrition, v.13, n.10, p.1145-1150, 2007.
GERMAN, A.J.; HERVERA, M.; HUNTER, L.; HOLDEN, S.L.; MORRIS, P.J.; BIOURGE, V.; TRAYHUM, P. Improvement in insulin resistance and reduction in plasma inflammatory adipokines after weight loss in obese dogs. Domestic Animal Endocrinology, v.37, n.4, p.214-226, 2009.
GRANT, R.W.; BOLLER, B.M.V.; RIDGE, T.K.; GRAVES, T.K.; SWANSON, K.S. Adipose tissue transcriptome changes during obesity development in female dogs. Physiology Genomics, v.43, n.6, p.295-307, 2011.
GREGOR, F.M.; HOTAMISLIGIL, G.S. Inflammatory mechanisms in obesity. Annual Review of Immunology, v.29, p.415-445, 2011.
GRUEN, M.L.; HAO, M.; PISTON, D.W.; HASTY, A.H. Leptin requires canonical migratory signaling pathways for induction of monocyte and macrophage chemotaxis. American Journal of Physiology-Cell Physiology, v.293, n.5, p.1481-1488, 2007.
HERNDON, A.M.; BRESHEARS, M.A.; MCFARLANE, D. Oxidative modification, inflammation and amyloid in the normal and diabetic cat pancreas. Journal of Comparative Pathology, v.151, n.4, p.352-362, 2014.
HIROSUMI, J.; TUNCMAN, G.; CHANG, L.; GÖRGÜN, C.Z.K.; UYSAL, T.; MAEDA, K.; KARIN, M.; HOTAMISLIGIL, G.S. A central role for JNK in obesity and insulin resistance. Nature, v.420, n.6913, p.333-336, 2002.
HOENIG, M. Nutrição na saúde e na doença: Metabolismo, Dieta e Obesidade. In: AUGUST, J.R. Medicina Interna de Felinos. 6ª ed., Rio de Janeiro: Elsevier, 2011. 928p.
HOENIG, M.; FERGUSON, D.C. Effects of neutering on hormonal concentrations and energy requirements in male and female cats. American Journal of Veterinary Research, v.63, n.5, p.634-639, 2002.
HOENIG, M.; PACH, N.P.; THOMASETH, K.; LE, A.; SCHAEFFER, D.; FERGUSON, D.C. Cats differ from other species in their cytokine and antioxidant enzyme response when developing obesity. Obesity, v.21, n.9, p.407-414, 2013.
HOTAMISLIGIL, G.S.; ARNER, P.; CARO, J.F.; ATKINSON, R.L.; SPIEGELMAN, B.M. Increased adipose tissue expression of tumor necrosis factor-αin human obesity and insulin resistance. Journal of Clinical Investigation, v.95, n.5, p.2409–2415, 1995.
HOTAMISLIGIL, G.S.; ERBAY, E. Nutrient sensing and inflammation in metabolic diseases. Nature Reviews Immunology, v.8, n.12, p.923–934, 2008.
HOTTA, K.; FUNAHASHI, T.; ARITA, Y.; TAKAHASHI, M.; MATSUDA, M.; OKAMOTO Y.; IWAHASHI, H.; KURIYAMA, H.; OUCHI, N.; MAEDA, K.; NISHIDA, M.; KIHARA, S.; SAKAI, N.; NAKAJIMA, T.; HASEGAWA, K.; MURUGUCHI, M.; OHMOTO, Y.; NAKAMURA, T.; YAMASHITA, S.; HANAFUSA, T.; MATSUZAWA, Y. Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients. Arteriosclerosis Thrombosis, and Vascular Biology, v.20, n.6, p.1595-1599, 2000.
KACZOROWSKI, D.C.; DINGER, M.E.; MEIKLE, P.J.; BOND, P.J.; FEBBRAIO, M.A. Evidence that TLR4 is not a receptor for saturated fatty acids but mediates lipid-induced inflammation by reprogramming macro-phage metabolism. Cell Metabolism, v.27, n.5, p.1096–1110, 2018.
KADOWAKI, T.; YAMAUCHI, T. Adiponectin and adiponectin receptors. Endocrine Reviews, v.26, n.3, p.439-451, 2005.
KAWAI, T.; AKIRA, S. TLR signaling. Seminars in Immunology, v.19, n.1, p.24-32, 2007.
KAWAI, T.; AUTIERI, M.V.; SCALIA, R. Adipose tissue inflammation and metabolic dysfunction in obesity. American Journal of Physiology, v.320, n.3, p.375-391, 2021.
KELLER, C.; LIESEGANG, A.; FREY, D.; WICHERT B. Metabolic response to three different diets in lean cats and cats predisposed to overweight. BMC Veterinary Research, v.184, n.13, p.1-10, 2017.
KERSHAW, E.E.; FLIER, J.S. Adipose tissue as an endocrine organ. The Journal of Clinical Endocrinology & Metabolism, v.89, n.6, p.2548–2556, 2004.
KIERSZENBAUM, A.L. Sistema tegumentar. In: KIERSZENBAUM, A.L.; TRES, L.T. Histologia e biologia celular: uma introdução à patologia. 2aed., Rio de Janeiro: Elsevier, cap.11, p.329-354, 2008.
KIM, M.J.; KIM, E.H.; PUN, N.T.; CHANG, J.H.; KIM, J.A.; JEONG, J.H.; CHOI, D.Y.; KIM, S.H.; PARK, P.H. Globular adiponectin inhibits lipopolysaccharide-primed inflammasomes activation in macrophages via autophagy induction: the critical role of AMPK signaling. International Journal of Molecular Science, v.18, n.6, p.1275, 2017.
KOHN, L.D.; WALLACE, B.; SCHWARTZ, F.; MCCALL, K. Is type 2 diabetes an autoimmune-inflammatory disorder of the innate immune system? Endocrinology, v.146, n.10, p.4189-4191, 2005.
LAFLAMME, D. P. Companion animals symposium: obesity in dogs and cats: what is wrong with being fat? Journal of Animal Science, v. 90, n.5, p. 1653–1662, 2012.
LAFONTAN M. Fat cells: afferent and efferent messages define new approaches to treat obesity. Annual Review of Pharmacology, v.45, n.1, p.119-146, 2005.
LAGO, R.; GÓMEZ, R.; LAGO, F.; GÓMEZ-REINO, J.; GUALILLO, O. Leptin beyond body weight regulation – current concepts concerning its role in immune function and inflammation. Cell Immunology, v.252, n.1-2, p.139–145, 2008.
LANCASTER, G.I.; LANGLEY, K. G.; BERGLUND, N.A.; KAMMOUN, H.L.; REIBE, S.; ESTEVEZ, E.; WEIR, J.; MELLETT, N.A.; PERNES, G.; CONWAY, J.R.W.; LEE, M.K.S.; TIMPSON, P.; MURPHY, A.J.; MASTERS, S.L.; GERONDAKIS, S.; BARTONICEK, N.; Evidence that TLR4 Is Not a Receptor for Saturated Fatty Acids but Mediates Lipid-Induced Inflammation by Reprogramming Macrophage Metabolism. Cell Metabolism, v.27, n.5, p.1096-1110, 2018.
LIU, J.; DIVOUX, A.; SUN, J.; ZHANG, J.; CLEMENT, K.; GLICKMAN, J.N.; SUKHOVA, G.K.; WOLTERS, P.J.; DU, J.; GORGUN, C.Z.; DORIA, A.; LIBBY, P.; BLUMBERG, R.S.; KAHN, B.B.; HOTAMISLIGIL, GS.; SHI, G.P. Genetic deficiency and pharmacological stabilization of mast cells reduce diet-induced obesity and diabetes in mice. Nature Medicine, v.15, n.8, p.940–45, 2009.
MAURY, E.; BRICHARD, S.M. Adipokine dysregulation, adipose tissue inflammation and metabolic syndrome. Molecular and Cellular Endocrinology, v.314, n.1, p.1-16, 2010.
MARTIN, L.; SILIART, B.; DUMON, H.; BACKUS, R.; BIOURGE, V.; NGUYEN, P. Leptin, body fat content and energy expenditure in intact and gonadectomized adult cats: a preliminary study. Journal of Animal Physiology and Animal Nutrition, v.85, n.7-8, p.195-199, 2001.
MAZAKI-TOVI, M.; BOLIN, S.R.; SCHENCK, P.A. Adipokines secretion in feline primary
adipose tissue culture in response to dietary fatty acids. BMC Veterinary Research, v.15, n.324, p.1-9, 2019.
MEDZHITOV, R. Origin and physiological roles of inflammation. Nature, v.454, p.428–435, 2008.
MURANAKA, S.; MORI, N.; HATANO, Y.; SAITO, T.R.; LEE, P.; KOJIMA, M.; KIGURE, M.; ARAI, T. Obesity induced changes to plasma adiponectin concentration and cholesterol lipoprotein composition profile in cats. Research in Veterinary Science, v.91, n.3, p.358-361, 2011.
MÜNZBERG, H.; BJÖRNHOLM, M.; BATES, S. H.; MYERS, M.G. Leptin receptor action and mechanisms of leptin resistance. Cellular and Molecular Life Sciences, v.62, n.6, p.642-652, 2005.
OHMURA, K.; ISHIMORI, N.; OHMURA, Y.; TOKUHARA, S.; NOZAWA, A.; HORII, S.; ANDOH, Y.; FUJII, S.; IWABUCHI, K.; ONOÉ, K.; TSUTSUI, H. Natural killer Tcells are involved in adipose tissues inflammation and glucose intolerance in diet-induced obese mice. Arteriosclerosis Thrombosis and Vascular Biology, v.30, n.2, p.193–99, 2010.
O’LEARY, C.A.; SEDHOM, M.; REEVE-JOHNSON, M.; MALLYON, J.; IRVINE, K.M. Expression profiling feline peripheral blood monocytes identifies a transcriptional signature associated with type two diabetes mellitus. Veterinary Immunology e Immunopathology, v.186, n.1-8, p.327-334, 2017.
PELLEGRINELLI, V.; CAROBBIO, S.; VIDAL-PUIG, A. Adipose tissue plasticity: how fat depots respond differently to pathophysiological cues. Diabetologia, v.59, n.1, p.1075-1088, 2016.
PRADHAN, A. D.; MANSON, J. E.; RIFAI, N.; BURING, J. E.; RIDKER, P. M. C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus. JAMA, v.286, n.2, p.327–334, 2001.
PRADO, W.L.; LOFRANO, M.C.; OYAMA, L.M.; DÂMASO, A.R. Obesidade e adipocinas inflamatórias: implicações práticas para a prescrição de exercício. Revista Brasileira de Medicina e Esporte, v.15, n.5, p.378-383, 2009.
RADIN, M.J.; SHARKEY, L.C.; HOLYCROSS, B.J. Adipokines: a review of biological and analytical principles and an update in dogs, cats, and horses. Veterinary Clinical Pathology, v.38, n.2, p.136–56, 2009.
SILVA, K.R. Avaliação clínico-laboratorial de gatos domésticos obesos e em sobrepeso, 2019. 72p. (Dissertação de Mestrado em Ciência Animal). Escola de Veterinária da Universidade Federal de Minas Gerais, 2019.
SOLINAS, G.; KARIN, M. JNK1 and IKKb: molecular links between obesity and metabolic dysfunction. The FASEB Journal, v.24, n.8, p.2596–2611, 2010.
TAKASHIMA, S.; NISHII, N.; KATO, A.; MATSUBARA, T.; SHIBATA, S.; KITAGAWA, H. Molecular cloning of feline resistin and the expression of resistin, leptin and adiponectin in the adipose tissue of normal and obese cats. The Journal of Veterinary Medical Science, v.78, n.1, p.23-28, 2016.
TAN, H.Y.; RAND, J.S.; MORTON, J.; M.; FLEEMAN, L.M.; ARMSTRONG, P.J.; CORADINI, M.; ISHIOKA, K.; VERKEST, K.R.; RICHARDS, A.A. RAWLINGS, J.M.; ROSE, J.S.; WHITEHEAD, J.P. Adiponectin profiles are affected by chronic and acute changes in carbohydrate intake in healthy cats. General and Comparative Endocrinology, v.171, n.3, p.468-474, 2011.
TIZARD, I.R. Defeitos Imunológicos Secundários. In: TIZARD, I.R. Imunologia Veterinária. 9a ed. Rio de Janeiro, cap.38, p.964-969, 2014. 568p.
TORNATORE, L.; THOTAKURA, A.K.; BENNETT, J.; MORETTI, M.; FRANZOSO, G. The nuclear factor κ B signaling pathway: integrating metabolism with inflammation. Trends in Cell Biology, v.22, n.11, p.557–566, 2012.
TVARIJONAVICIUTE, A.; CERON, J.J.; HOLDEN, S.L.; MORRIS, P.J.; BIOURGE, V.; GERMAN, A.J. Effects of weight loss in obese cats on biochemical analytes related to inflammation and glucose homeostasis. Domestic Animal Endocrinology, v.42, n.3, p.129-141, 2011.
UNAMUNO, X.; GÓMEZ-AMBROSI, J.; RODRÍGUEZ, A.; BERRECIL, S.; FRUHBECK, G.; CATALÁN, V. Adipokine dysregulation and adipose tissue inflammation in human obesity. Europan Journal of Clinical Investigation, v.8, n.9, p.129-197, 2018.
VELLOSO, L.A. O Controle hipotalâmico da fome e da termogênese – implicações no desenvolvimento da obesidade. Arquivos Brasileiros de Endocrinologia e Metabologia, v.50, n.2, p.165-176, 2006.
VIRTUE, S.; VIDAL-PUIG, A. Adipose tissue expandability, lipotoxicity and the Metabolic
Syndrome-an allostatic perspective. Biochimica et Biophysica Acta, v.1801, n.3, p.338-349, 2010.
VISSER, M.; BOUTER, L.M.; MCQUILLAN, G.M.; WENER, M.H.; HARRIS, T.B. Elevated C-reactive protein levels in overweight and obese adults. JAMA, v.282, n.22, p.2131-2135, 1999.
WANG, C.H.; WANG, C.C.; HUANG, H.C.; WEI, Y.H. Mitochondrial dysfunction leads to impairment of insulin sensitivity and adiponectin secretion in adipocytes. The FEBS Journal, v.280, n.4, p.1039-1050, 2013.
WOO, C.Y.; JANG, J.E.; LEE, S.E.; KOH, E.H.; LEE, K.U. Mitochondrial dysfunction in adipocytes as a primary cause of adipose tissue inflammation, v.43, n.3, p.247-256, 2019.
YE, J.; GAO, Z.; YIN, J.; HE, Q. Hypoxia is a potential risk factor for chronic inflammation and adiponectin reduction in adipose tissue of ob/ob and dietary obese mice. American Journal of Physiology-Endocrinology and Metabolism, v.293, n.4, p.1118-1128, 2007.
ZAPATA, R.C.; MEACHEM, M.D.; CARDOSO, N.C.; MEHAIN, S.O.; MCMILLAN, C.J.; SNEAD, E.R.; CHELIKANI, P.K. Differential circulating concentrations of adipokines, glucagon and adropin in a clinical population of lean, overweight and diabetic cats. BMC Veterinary Research, v.13, n.85, p.1-9, 2017.
ZORAN, D.L. Obesity in Dogs and Cats: A Metabolic and Endocrine Disorder. Veterinary Clinics of North America: Small Animal Practice, v.40, n.2, p.205–210, 2010.