Modelos experimentais de obesidade: análise crítica do perfil metabólico e da aplicabilidade
DOI:
https://doi.org/10.34019/1982-8047.2018.v44.14053Palavras-chave:
Metabolismo, Modelos animais, Obesidade, RoedoresResumo
Introdução: a prevalência da obesidade e de outras doenças relacionadas está aumentando em todo o mundo de forma preocupante. Caracterizada pelo aumento do peso corporal ou do acúmulo excessivo de gordura corporal, a obesidade tem sido associada ao aumento da mortalidade decorrente de maior incidência de hipertensão, diabetes e vários tipos de câncer. Os modelos animais fornecem dados fundamentais para a compreensão dos parâmetros básicos que regulam os componentes do nosso balanço energético. Objetivo: esta revisão selecionou artigos que utilizaram modelos animais (ratos e camundongos) de obesidade focando nas principais alterações metabólicas causadas pela obesidade com o objetivo de apresentar os principais modelos utilizados nos últimos 5 anos. Material e Métodos: Foram realizadas duas buscas na base de dados PubMed utilizando as expressões: “obesity” AND “metabolism” AND “animal model” AND “mice” e “obesity” AND “metabolism” AND “animal model” AND “rat”, sendo selecionados os estudos considerados mais relevantes a partir dos critérios: descrição detalhada do modelo experimental e análise dos parâmetros metabólicos de interesse: peso, perfil lipídico e perfil glicêmico. Outras referências foram utilizadas para elucidar melhor os modelos encontrados e também aqueles que não foram citados, mas, que possuem importância no entendimento da evolução dos modelos animais de obesidade. Resultados: A espécie mais utilizada foi o camundongo, o sexo predominante foi o masculino, a faixa etária dos roedores variou de neonatos até 44 semanas e o período de acompanhamento chegou até 53 semanas. A obesidade foi confirmada pelo aumento significativo do peso e na maioria dos estudos foram encontradas alterações no metabolismo lipídico e glicêmico. Encontramos cinco grupos de mecanismos de indução da obesidade porém a maioria dos estudos utilizou dietas hiperlipídicas, modelo que mais se assemelha às alterações metabólicas encontradas em humanos. Conclusão: Investigar as causas e efeitos da obesidade induzida em modelos experimentais pode fornecer uma melhor compreensão da fisiopatologia da obesidade, e proporcionar novas opções de prevenção e tratamento.
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Referências
ALZAMENDI, A. et al. High risk of metabolic and adipose tissue dysfunctions in adult male progeny, due to prenatal and adulthood malnutrition induced by fructose rich diet. Nutrients, v. 8, n. 3, p.178, mar. 2016.
BAHARY, N. et al. Molecular mapping of the mouse db mutation. Proceedings of the National Academy of Sciences of the United States of America, v. 87, n. 21, p. 8642-8646, nov.1990.
BALDASSANO, S. et al. Glucagon-like peptide-2 treatment improves glucose dysmetabolism in mice fed a high-fat diet. Endocrine, v. 54, n. 3, p. 648-656, dec. 2016.
BAO, D. et al. Preliminary characterization of a leptin receptor knockout rat created by CRISPR/Cas9 system. Scientific Reports, v. 5, p. 15942, nov. 2015.
BARANOWSKA, B. et al. The role of neuropeptides in the disturbed control of appetite and hormone secretion in eating disorders. Neuroendocrinology Letters, v. 24, n. 6, p. 431-434, dec. 2003.
BARRETT, P., J. G. et al. Preclinical models for obesity research. Disease Model Mechanisms, v. 9, n. 11, p. 1245-1255, nov. 2016.
BAYOL, S. A. et al. A maternal 'junk food' diet in pregnancy and lactation promotes an exacerbated taste for 'junk food' and a greater propensity for obesity in rat offspring. British Journal of Nutrition, v. 98, n. 4, p. 843-851, oct. 2007.
BERG, C., G. et al. Eating patterns and portion size associated with obesity in a Swedish population. Appetite, v. 52, n. 1, p. 21-26, feb. 2009.
BRAY, G. A. The Zucker-fatty rat: a review. Federation Proceedings, v. 36, n. 2, p. 148-53, feb. 1977.
CHAPUT, J. P. et al. Findings from the Quebec family study on the etiology of obesity: genetics and environmental highlights. Current Obesity Reports, v. 3, p. 54-66, 2014.
D'SOUZA, M. et al. Leptin deficiency in rats results in hyperinsulinemia and impaired glucose homeostasis. Endocrinology, v. 155, n. 4, p. 1268-79, apr. 2014.
DALVI, P. S.; BELSHAM, D. D. Glucagon-like peptide-2 directly regulates hypothalamic neurons expressing neuropeptides linked to appetite control in vivo and in vitro. Endocrinology, v. 153, n. 5, p. 2385-97, may. 2012.
DONNER, D. G. et al. Impact of diet-induced obesity and testosterone deficiency on the cardiovascular system: a novel rodent model representative of males with testosterone-deficient metabolic syndrome (TDMetS). PLoS One, v. 10, n. 9, p. e0138019, 2015.
EZQUER, F. et al. Administration of multipotent mesenchymal stromal cells restores liver regeneration and improves liver function in obese mice with hepatic steatosis after partial hepatectomy. Stem Cell Research & Therapy, v. 8, n. 1, p. 20, jan. 2017.
FERRAMOSCA, A. et al. A high-fat diet negatively affects rat sperm mitochondrial respiration. Andrology, v. 4, n. 3, p. 520-525, may. 2016.
GRASA-LOPEZ, A. et al. Undaria pinnatifida and fucoxanthin ameliorate lipogenesis and markers of both inflammation and cardiovascular dysfunction in an animal model of diet-induced obesity. Marine Drugs, v. 14, n. 8, aug. 2016.
GUH, D. P. et al. The incidence of co-morbidities related to obesity and overweight: a systematic review and meta-analysis. BMC Public Health, v. 9, p. 88, mar. 2009.
HAN, J. M. et al. Repeated sense of hunger leads to the development of visceral obesity and metabolic syndrome in a mouse model. PLoS One, v. 9, n. 5, p. e98276. 2014.
HRUBY, A. et al. Determinants and consequences of obesity. American Journal of Public Health, v. 106, n. 9, p. 1656-1662, sep. 2016.
HVID, H. et al. Treatment with insulin analog X10 and IGF-1 increases growth of colon cancer allografts. PLoS One, v. 8, n. 11, p. e79710, 2013.
INGALLS, A. M. et al. Obese, a new mutation in the house mouse. Journal of Heredity, v. 41, n. 12, p. 317-318, dec. 1950.
ISHII, Y. et al. Female spontaneously diabetic Torii fatty rats develop nonalcoholic steatohepatitis-like hepatic lesions. World Journal of Gastroenterology, v. 21, n. 30, p. 9067-9078, aug. 2015.
JAAKKOLA, J. et al. Eating behavior influences diet, weight, and central obesity in women after pregnancy. Nutrition, v. 29, n. 10, p.1209-1213, oct. 2013.
KAIYALA, K. J.; SCHWARTZ, M. W. Toward a more complete (and less controversial) understanding of energy expenditure and its role in obesity pathogenesis. Diabetes, v. 60, n. 1, p. 17-23. jan. 2011.
KANASAKI, K.; KOYA, D. Biology of obesity: lessons from animal models of obesity. Journal of Biomedicine and Biotechnology, v. 2011, p. 197636, 2011.
KOPELMAN, P. Health risks associated with overweight and obesity. Obesity Reviews, v. 8 Suppl 1, p. 13-17, mar. 2007.
KULKARNI, N. M. et al. A novel animal model of metabolic syndrome with non-alcoholic fatty liver disease and skin inflammation. Pharmaceutical Biology, v. 53, n. 8, p. 1110-1117, aug. 2015.
LAI, Y. S. et al. Mass-spectrometry-based serum metabolomics of a C57BL/6J mouse model of high-fat-diet-induced non-alcoholic fatty liver disease development. Journal of Agricultural and Food Chemistry, v. 63, n. 35, p. 7873-7884, sep. 2015.
LI, J. et al. The Aqueous Extract of Gynura divaricata (L.) DC. Improves glucose and lipid metabolism and ameliorates type 2 diabetes mellitus. Evidence-Based Complementary and Alternative Medicine, v. 2018, p. 8686297. 2018.
LI, N. et al. Short-term moderate diet restriction in adulthood can reverse oxidative, cardiovascular and metabolic alterations induced by postnatal overfeeding in mice. Scientific Reports, v. 6, p.30817, jul. 2016.
LUTZ, T. A.; WOODS, S. C. Overview of animal models of obesity. Current Protocols in Pharmacology, v. Chapter 5, p. Unit5 61, sep. 2012.
MA, Y. et al. Association between eating patterns and obesity in a free-living US adult population. American Journal of Epidemiology, v. 158, n. 1, p. 85-92, jul. 2003.
MADHAVADAS, S. et al. Amyloid beta lowering and cognition enhancing effects of ghrelin receptor analog [D-Lys (3)] GHRP-6 in rat model of obesity. Indian Journal of Biochemistry & Biophysics, v. 51, n. 4, p. 257-262, aug. 2014.
MARIN, V. et al. An Animal model for the juvenile non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. PLoS One, v. 11, n. 7, p. e0158817, 2016.
MARINE-CASADO, R. et al. Intake of an obesogenic cafeteria diet affects body weight, feeding behavior, and glucose and lipid metabolism in a photoperiod-dependent manner in f344 rats. Frontiers in Physiology, v. 9, p. 1639, 2018.
MONTALVO-MARTINEZ, L., R. et al. Maternal overnutrition programs central inflammation and addiction-like behavior in offspring. BioMed Research International, v. 2018, p. 8061389, 2018.
NAKAGAWA, T. et al. Effects of chronic administration of sibutramine on body weight, food intake and motor activity in neonatally monosodium glutamate-treated obese female rats: relationship of antiobesity effect with monoamines. Experimental Animals, v. 49, n. 4, p. 239-49, oct. 2000.
NAKAHARA, K. et al. Characterization of a novel genetically obese mouse model demonstrating early onset hyperphagia and hyperleptinemia. American Journal of Physiology-Endocrinology and Metabolism, v. 305, n. 3, p. E451-63, aug. 2013.
NASCIMENTO-SALES, M. et al. Is the FVB/N mouse strain truly resistant to diet-induced obesity? Physiological Reports, v.5, n.9, may. 2017.
OJO, B. et al. Wheat germ supplementation alleviates insulin resistance and cardiac mitochondrial dysfunction in an animal model of diet-induced obesity. British Journal of Nutrition, v. 118, n. 4, p. 241-249, aug. 2017.
OLIVEIRA, L. S. et al. The inflammatory profile and liver damage of a sucrose-rich diet in mice. Journal of Nutritional Biochemistry, v. 25, n. 2, p.193-200, feb. 2014.
OLIVEIRA, P. S. et al. Eugenia uniflora fruit (red type) standardized extract: a potential pharmacological tool to diet-induced metabolic syndrome damage management. Biomedicine & Pharmacotherapy, v. 92, p.935-941, aug. 2017.
ORLANDO, G. et al. Effects of Kisspeptin-10 on hypothalamic neuropeptides and neurotransmitters involved in appetite control. Molecules, v. 23, n. 12, nov. 2018.
PORRAS, D. et al. Protective effect of quercetin on high-fat diet-induced non-alcoholic fatty liver disease in mice is mediated by modulating intestinal microbiota imbalance and related gut-liver axis activation. Free Radical Biology & Medicine, v. 102, p. 188-202, jan. 2017.
PORTELLA, A. K. et al. Litter size reduction alters insulin signaling in the ventral tegmental area and influences dopamine-related behaviors in adult rats. Behavioural Brain Research, v. 278, p. 66-73, jan. 2015.
SADOWSKA, J. et al. Metabolic risk factors in mice divergently selected for BMR fed high fat and high carb diets. PLoS One, v. 12, n. 2, p. e0172892, 2017.
SALEH, S. et al. Modulation of diabetes and dyslipidemia in diabetic insulin-resistant rats by mangiferin: role of adiponectin and TNF-alpha. Anais da Academia Brasileira de Ciências, v. 86, n. 4, p. 1935-1948, dec. 2014.
SANGHEZ, V. et al. Psychosocial stress induces hyperphagia and exacerbates diet-induced insulin resistance and the manifestations of the Metabolic Syndrome. Psychoneuroendocrinology, v. 38, n. 12, p.2933-2942, dec 2013.
SCHMIDT, I. et al. The effect of leptin treatment on the development of obesity in overfed suckling Wistar rats. International journal of obesity and related metabolic disorders, v. 25, n. 8, p. 1168-1174, aug. 2001.
SHARMA, B. R. et al. Caulerpa okamurae extract inhibits adipogenesis in 3T3-L1 adipocytes and prevents high-fat diet-induced obesity in C57BL/6 mice. Nutrition Research, v. 47, p. 44-52, nov. 2017.
SHIMIZU, Y. et al. Enhanced responses of the chorda tympani nerve to sugars in the ventromedial hypothalamic obese rat. Journal of Neurophysiology, v. 90, n. 1, p. 128-133, jul. 2003.
SINGER, K.; LUMENG, C. N. The initiation of metabolic inflammation in childhood obesity. Journal of Clinical Investigation, v. 127, n. 1, p. 65-73, jan. 2017.
SLADEK, C. D. et al. The "metabolic sensor" function of rat supraoptic oxytocin and vasopressin neurons is attenuated during lactation but not in diet-induced obesity. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, v. 310, n. 4, p. R337-345, feb. 2015.
SPEAKMAN, J. et al. Animal models of obesity. Obesity Reviews, v. 8 Suppl 1, p. 55-61, mar. 2007.
______. The contribution of animal models to the study of obesity. Laboratory Animals, v. 42, n. 4, p. 413-432, oct. 2008.
SUZUKI, Y. et al. Sex difference of hyperinsulinemia in the C57BL/6J-Daruma (obese) mouse. Journal of Veterinary Medical Science, v. 79, n. 7, p. 1284-1293, jul. 2017.
TASYUREK, H. M. et al. HIV-based lentivirus-mediated vasoactive intestinal peptide gene delivery protects against DIO animal model of Type 2 diabetes. Gene Therapy, v. 25, n. 4, p. 269-283, jul. 2018.
TUNG, Y. C. et al. Piceatannol exerts anti-obesity effects in C57BL/6 mice through modulating adipogenic proteins and gut microbiota. Molecules, v. 21, n. 11, oct. 2016.
VIGITEL. Vigilância de fatores de risco e proteção para doenças crônicas por inquérito telefônico. Brasil. Ministério da Saúde, v. 2016. 2016.
VON DIEMEN, V. et al. Experimental model to induce obesity in rats. Acta Cirurgica Brasileira, v. 21, n. 6, p. 425-429, nov./dec. 2006.
WATANABE, S. et al. A high-fat and high-cholesterol diet induces cardiac fibrosis, vascular endothelial, and left ventricular diastolic dysfunction in SHRSP5/Dmcr rats. Journal of Atherosclerosis and Thrombosis, v. 25, n. 5, p. 439-453, may. 2018.
WHO, W. H. O. Obesity and overweight. World Health Organization, 10/29/2018, p.http://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight. 2016.
WILDING, J. P. Neuropeptides and appetite control. Diabetic Medicine, v. 19, n. 8, p. 619-627, aug. 2002.
XU, G. et al. Activation of pluripotent genes in hepatic progenitor cells in the transition of nonalcoholic steatohepatitis to pre-malignant lesions. Laboratory Investigation, v. 97, n. 10, p. 1201-1217, oct. 2017.
ZEENI, N. et al. Cafeteria diet-fed mice is a pertinent model of obesity-induced organ damage: a potential role of inflammation. Inflammation Research, v. 64, n. 7, p.501-512, jul. 2015.
ZHANG, Y. et al. Positional cloning of the mouse obese gene and its human homologue. Nature, v. 372, n. 6505, p. 425-432, dec. 1994.
ZUCKER, L.; ZUCKER, T. Fatty, a new mutation in the rat. Journal of Heredity. v. 52, p. 275-278, 1961.
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