Hostname: page-component-cd9895bd7-8ctnn Total loading time: 0 Render date: 2024-12-27T11:12:18.952Z Has data issue: false hasContentIssue false
  • English
  • Français

(-)-Epicatechin reduces adiposity in male offspring of obese rats

Published online by Cambridge University Press:  10 June 2019

Sergio De los Santos ,
Luis Antonio Reyes-Castro ,
Ramón Mauricio Coral-Vázquez ,
Juan Pablo Méndez ,
Marcela Leal-García ,
Elena Zambrano  and
Patricia Canto Open the ORCID record for Patricia Canto [Opens in a new window]
Sergio De los Santos
Affiliation:
Unidad de Investigación en Obesidad, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad de México, México
Luis Antonio Reyes-Castro
Affiliation:
Departamento de Biología de Reproducción, Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán,”Ciudad de México, México
Ramón Mauricio Coral-Vázquez
Affiliation:
Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Ciudad de México, México Subdirección de Enseñanza e Investigación, Centro Médico Nacional “20 de Noviembre,”Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado, Ciudad de México, México
Juan Pablo Méndez
Affiliation:
Unidad de Investigación en Obesidad, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad de México, México Subdirección de Investigación Clínica, Dirección de Investigación, Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán,”Ciudad de México, México
Marcela Leal-García
Affiliation:
Unidad de Investigación en Obesidad, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad de México, México
Elena Zambrano
Affiliation:
Departamento de Biología de Reproducción, Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán,”Ciudad de México, México
Patricia Canto*
Affiliation:
Unidad de Investigación en Obesidad, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad de México, México Subdirección de Investigación Clínica, Dirección de Investigación, Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán,”Ciudad de México, México
*
Address for correspondence: Patricia Canto, Unidad de Investigación en Obesidad, Facultad de Medicina, Universidad Nacional Autónoma de México & Subdirección de Investigación Clínica, Dirección de Investigación, Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán”, Vasco de Quiroga No. 15, Col. Sección XVI, Delegación Tlalpan, CP 14000, Mexico, D.F., México. Emails: ipcanto@yahoo.com.mx; ipcanto64@gmail.com
Get access Rights & Permissions [Opens in a new window]

Abstract

Objective:

To determine whether (-)-epicatechin (Epi) could decrease visceral adipose tissue and improve the metabolic profile of male offspring rats, after maternal obesity was induced by a high-fat diet (HFD).

Design:

Maternal obesity in albino Wistar rats was induced with a HFD, whereas male offspring were fed with chow diet throughout the study. Eight male offspring per group, from different litters, were randomly assigned to the experimental or to the control groups. In the experimental group, Epi was administered at a dose of 1 mg/kg of body weight to the male offspring twice daily for two weeks, beginning at postnatal day (PND).

Main measures:

Weight of visceral adipose tissue, adipocyte size, and several metabolic parameters.

Results:

Epi administration in the male offspring induced a significant decrease in the amount of visceral fat (11.61 g less, P < 0.05) and in the size of adipose cells (28% smaller, P < 0.01). Besides, Epi was able to decrease insulin, leptin, and Homeostasis Model Assessment -Insulin Resistance (HOMA-IR) (P < 0.05), as well as triglycerides, when the experimental group was compared to the untreated male offspring of obese rats (P < 0.01).

Conclusions:

Epi administration can reverse the negative effects that maternal obesity has on the male offspring. This could be because Epi reduces the amount of visceral fat and improves metabolic profile.

Keywords

(-)-epicatechinmale offspringmaternal obesityrats
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 11 , Issue 1 , February 2020 , pp. 37 - 43
Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2019 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Chan, RSM, Woo, J. Prevention of overweight and obesity: how effective is the current public health approach. Int J Environ Res Public Health. 2010; 7, 765–783.CrossRefGoogle ScholarPubMed
Pi-Sunyer, X. The medical risks of obesity. Postgrad Med. 2009; 121, 21–33.CrossRefGoogle ScholarPubMed
Kotsis, V, Jordan, J, Micic, D, et al. Obesity and cardiovascular risk: a call for action from the European Society of Hypertension Working Group of Obesity, Diabetes and the High-risk Patient and European Association for the Study of Obesity: part A: mechanisms of obesity induced hypertension, diabetes and dyslipidemia and practice guidelines for treatment. J Hypertens. 2018; 36, 1427–1440.CrossRefGoogle Scholar
Collins, KH, Herzog, W, MacDonald, GZ, et al. Obesity, metabolic syndrome, and musculoskeletal disease: common inflammatory pathways suggest a central role for loss of muscle integrity. Front Physiol. 2018; 9, 112.CrossRefGoogle ScholarPubMed
Argolo, DF, Hudis, CA, Iyengar, NM. The impact of obesity on breast cancer. Curr Oncol Rep. 2018; 20, 47.CrossRefGoogle ScholarPubMed
Cohen, DA. Obesity and the built environment: changes in environmental cues cause energy imbalances. Int J Obes. 2008; 32, S137–S142.CrossRefGoogle ScholarPubMed
Jiménez-Pavón, D, Kelly, J, Reilly, JJ. Associations between objectively measured habitual physical activity and adiposity in children and adolescents: systematic review. Int J Pediatr Obes. 2010; 5, 3–18.CrossRefGoogle ScholarPubMed
Zambrano, E, Ibáñez, C, Martínez-Samayoa, PM, et al. Maternal obesity: lifelong metabolic outcomes for offspring from poor developmental trajectories during the perinatal period. Arch Med Res. 2016; 47, 1–12.CrossRefGoogle ScholarPubMed
Taveras, EM, Rifas-Shiman, SL, Belfort, MB, et al. Weight status in the first 6 months of life and obesity at 3 years of age. Pediatrics 2009; 123, 1177–1183.CrossRefGoogle ScholarPubMed
Khan, I, Dekou, V, Hanson, M, et al. Predictive adaptive responses to maternal high-fat diet prevent endothelial dysfunction but not hypertension in adult rat offspring. Circulation. 2004; 110, 1097–1102.CrossRefGoogle Scholar
Wright, CS, Rifas-Shiman, SL, Rich-Edwards, JW, et al. Intrauterine exposure to gestational diabetes, child adiposity, and blood pressure. Am J Hypertens. 2009; 22, 215–220.CrossRefGoogle ScholarPubMed
Eberle, C, Merki, E, Yamashita, T, et al. Maternal immunization affects in utero programming of insulin resistance and type 2 diabetes. PLoS ONE. 2012; 7, e45361.CrossRefGoogle ScholarPubMed
Jones, HN, Woollett, LA, Barbour, N, et al. High-fat diet before and during pregnancy causes marked up-regulation of placental nutrient transport and fetal overgrowth in C57/BL6 mice. FASEB J. 2009; 23, 271–278.CrossRefGoogle ScholarPubMed
Zambrano, E, Nathanielsz, PW. Mechanisms by which maternal obesity programs offspring for obesity: evidence from animal studies. Nutr Rev. 2013; 71, S42–S54.CrossRefGoogle ScholarPubMed
Meydani, M, Hasan, ST. Dietary polyphenols and obesity. Nutrients. 2010; 2, 737–751.CrossRefGoogle ScholarPubMed
Harnly, JM, Doherty, RF, Beecher, GR, et al. Flavonoid content of US fruits, vegetables, and nuts. J Agric Food Chem. 2006; 54, 9966–77.CrossRefGoogle Scholar
Ramirez-Sanchez, I, Maya, L, Ceballos, G, et al. (-)-Epicatechin activation of endothelial cell endothelial nitric oxide synthase, nitric oxide, and related signaling pathways. Hypertension. 2010; 55, 1398–1405.CrossRefGoogle ScholarPubMed
Schroeter, H, Heiss, C, Balzer, J, et al. (-)-Epicatechin mediates beneficial effects of flavanol-rich cocoa on vascular function in humans. Proc Natl Acad Sci USA. 2006; 103, 1024–1029.CrossRefGoogle ScholarPubMed
Nogueira, L, Ramirez-Sanchez, I, Perkins, GA, et al. (-)-Epicatechin enhances fatigue resistance and oxidative capacity in mouse muscle. J Physiol. 2011; 589, 4615–4631.CrossRefGoogle ScholarPubMed
Ramirez-Sanchez, I, De los Santos, S, Gonzalez-Basurto, S, et al. (-)-Epicatechin improves mitochondrial-related protein levels and ameliorates oxidative stress in dystrophic δ-sarcoglycan null mouse striated muscle. FEBS J. 2014; 281, 5567–5580.CrossRefGoogle ScholarPubMed
De Los Santos, S, Palma-Flores, C, Zentella-Dehesa, A, et al. (-)-epicatechin inhibits development of dilated cardiomyopathy in δ sarcoglycan null mouse. Nutr Metab Cardiovasc Dis. 2018; S0939-4753(18)30222-9.CrossRefGoogle ScholarPubMed
De Los Santos, S, García-Pérez, V, Hernández-Reséndiz, S, et al. (-)-Epicatechin induces physiological cardiac growth by activation of the PI3K/Akt pathway in mice. Mol Nutr Food Res. 2017; 61.Google ScholarPubMed
Hoek-van den Hil, EF, van Schothorst, EM, van der Stelt, I, et al. Direct comparison of metabolic health effects of the flavonoids quercetin, hesperetin, epicatechin, apigenin and anthocyanins in high-fat-diet-fed mice. Genes Nutr. 2015; 10, 469.CrossRefGoogle ScholarPubMed
Gutiérrez-Salmeán, G, Ortiz-Vilchis, P, Vacasey del, CM, et al. Effects of (-)-epicatechin on a diet-induced rat model of cardiometabolic risk factors. Eur J Pharmacol. 2014; 728, 24–30.CrossRefGoogle ScholarPubMed
Sano, T, Nagayasu, S, Suzuki, S, et al. Epicatechin downregulates adipose tissue CCL19 expression and thereby ameliorates diet-induced obesity and insulin resistance. Nutr Metab Cardiovasc Dis. 2017; 27, 249–259.CrossRefGoogle ScholarPubMed
Cremonini, E, Bettaieb, A, Haj, FG, et al. (-)-Epicatechin improves insulin sensitivity in high fat diet-fed mice. Arch Biochem Biophys, 2016; 599, 13–21.CrossRefGoogle ScholarPubMed
Bettaieb, A, Vazquez-Prieto, MA, Rodriguez-Lanzi, C, et al. (-)-Epicatechin mitigates high-fructose-associated insulin resistance by modulating redox signaling and endoplasmic reticulum stress. Free Radic Biol Med. 2014; 72, 247–56.CrossRefGoogle ScholarPubMed
Bettaieb, A, Cremonini, E, Kang, H, et al. Anti-inflammatory actions of (-)-epicatechin in the adipose tissue of obese mice. Int J Biochem Cell Biol. 2016; 81(Pt B), 383–92.CrossRefGoogle ScholarPubMed
Zambrano, E, Bautista, CJ, Deás, M, et al. A low maternal protein diet during pregnancy and lactation has sex- and window of exposure-specific effects on offspring growth and food intake, glucose metabolism and serum leptin in the rat. J Physiol 2006; 571, 221–230.CrossRefGoogle ScholarPubMed
Fischer, AH, Jacobson, KA, Rose, J, Zeller, R. Hematoxylin and eosin staining of tissue and cell sections. CSH Protoc. 2008; pdb.prot4986.Google ScholarPubMed
Vega, CC, Reyes-Castro, LA, Rodríguez-González, GL, et al. Resveratrol partially prevents oxidative stress and metabolic dysfunction in pregnant rats fed a low protein diet and their offspring. J Physiol 2016; 594, 1483–1499.CrossRefGoogle ScholarPubMed
Dell, RB, Holleran, S, Ramakrishnan, R. Sample Size Determination. ILAR J. 2002; 43, 207–213.CrossRefGoogle ScholarPubMed
Nathanielsz, PW, Ford, SP, Long, NM, et al. Interventions to prevent adverse fetal programming due to maternal obesity during pregnancy. Nutr Rev. 2013; 71, S78–S87.CrossRefGoogle ScholarPubMed
Zambrano, E, Martínez-Samayoa, PM, Rodríguez-González, GL, et al. Dietary intervention prior to pregnancy reverses metabolic programming in male offspring of obese rats. J Physiol. 2010; 588, 1791–1799.CrossRefGoogle ScholarPubMed
Vega, CC, Reyes-Castro, LA, Bautista, CJ, et al. Exercise in obese female rats has beneficial effects on maternal and male and female offspring metabolism. Int J Obes. 2015; 39, 712–719.CrossRefGoogle ScholarPubMed
Rodríguez-González, GL, Vega, CC, Boeck, L, et al. Maternal obesity and overnutrition increase oxidative stress in male rat offspring reproductive system and decrease fertility. Int J Obes. 2015; 39, 549–556.CrossRefGoogle ScholarPubMed
Parlee, SD, MacDougald, OA. Maternal nutrition and risk of obesity in offspring: the Trojan horse of developmental plasticity. Biochim Biophys Acta. 2014; 1842, 495–506.CrossRefGoogle ScholarPubMed
Williams, L, Seki, Y, Vuguin, PM, et al. Animal models of in utero exposure to a high fat diet: a review. Biochem Biophys Acta. 2014; 1842, 507–519.Google ScholarPubMed
Portha, B, Chavey, A, Movassat, J. Early-life origins of type 2 diabetes: fetal programming of the beta-cell mass. Exp Diabetes Res. 2011; 2011, 105076.CrossRefGoogle ScholarPubMed
Ingelfinger, JR, Nuyt, A-M. Impact of fetal programming, birth weight, and infant feeding on later hypertension. J Clin Hypertens (Greenwich). 2012; 14, 365–371.CrossRefGoogle ScholarPubMed
Sarr, O, Yang, K, Regnault, TRH. In utero programming of later adiposity: the role of fetal growth restriction. J Pregnancy. 2012; 2012, 34758.CrossRefGoogle ScholarPubMed
Desai, M, Beall, M, Ross, MG. Developmental origins of obesity: programmed adipogenesis. Curr Diab Rep. 2013; 13, 27–33.CrossRefGoogle ScholarPubMed
Heiss, C, Dejam, A, Kleinbongard, P, et al. Vascular effects of cocoa rich in flavan-3-ols. JAMA. 2013; 290, 1030–1031.CrossRefGoogle Scholar
Gutiérrez-Salmeán, G, Meaney, E, Lanaspa, MA, et al. A randomized, placebo-controlled, double-blind study on the effects of (–)-epicatechin on the triglyceride/HDLc ratio and cardiometabolic profile of subjects with hypertriglyceridemia: Unique in vitro effects. Int J Cardiol. 2016; 223, 500–506CrossRefGoogle ScholarPubMed
Santos, M, Rodríguez-González, GL, Ibáñez, C, et al. Adult exercise effects on oxidative stress and reproductive programming in male offspring of obese rats. Am J Physiol Regul Integr Comp Physiol. 2015; 308, R219–R225.CrossRefGoogle ScholarPubMed
Fan, W, Evans, RM. Exercise mimetics: impact on health and performance. Cell Metab. 2017; 25, 242–247.CrossRefGoogle ScholarPubMed
Moreno-Ulloa, A, Cid, A, Rubio-Gayosso, I, et al. Effects of (-)-epicatechin and derivatives on nitric oxide-mediated induction of mitochondrial proteins. Bioorg Med Chem Lett. 2013; 23, 4441–6.CrossRefGoogle ScholarPubMed
Varela, CE, Rodriguez, A, Romero-Valdovinos, M, et al. Browning effects of (-)-epicatechin on adipocytes and white adipose tissue. Eur J Pharmacol. 2017; 811, 48–59.CrossRefGoogle ScholarPubMed
Montague, CT, O’Rahilly, S. The perils of portliness: causes and consequences of visceral adiposity. Diabetes. 2000; 49, 883–888.CrossRefGoogle ScholarPubMed
Kintscher, U, Hartge, M, Hess, K, et al. T-lymphocyte infiltration in visceral adipose tissue: a primary event in adipose tissue inflammation and the development of obesity-mediated insulin resistance. Arterioscler Thromb Vasc Biol. 2008; 28, 1304–10.CrossRefGoogle ScholarPubMed
Weisberg, SP, McCann, D, Desai, M, et al. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest. 2003; 112, 1796–1808.CrossRefGoogle ScholarPubMed
Liu, KH, Chan, YL, Chan, WB, et al. Mesenteric fat thickness is an independent determinant of metabolic syndrome and identifies subjects with increased carotid intima-media thickness. Diabetes Care. 2006; 29, 379–84.CrossRefGoogle ScholarPubMed
Choe, SS, Huh, JY, Hwang, IJ, et al. Adipose tissue remodeling: its role in energy metabolism and metabolic disorders. Front Endocrinol. 2016; 13, 7–30.Google Scholar
Hertzer, KM, Xu, M, Moro, A, et al. Robust early inflammation of the peripancreatic visceral adipose tissue during diet-induced obesity in the KrasG12D model of pancreatic cancer. Pancreas. 2016; 45(3), 458–65.CrossRefGoogle ScholarPubMed
Jensen, MD. Role of body fat distribution and the metabolic complications of obesity. J Clin Endocrinol Metab 2008; 93, S57–S63.CrossRefGoogle ScholarPubMed
Cordero-Herrera, I, Chen, X, Ramos, S, Devaraj, S. (-)-Epicatechin attenuates high-glucose-induced inflammation by epigenetic modulation in human monocytes. Eur J Nutr. 2017; 56(3), 1369–73.CrossRefGoogle ScholarPubMed