Hostname: page-component-cd9895bd7-lnqnp Total loading time: 0 Render date: 2024-12-19T05:21:33.490Z Has data issue: false hasContentIssue false
  • English
  • Français

Hepatic lipid metabolism in adult rats using early weaning models: sex-related differences

Part of: DOHaD Research in Latin-American

Published online by Cambridge University Press:  10 June 2020

Iala Milene Bertasso ,
Carla Bruna Pietrobon ,
Beatriz Souza da Silva ,
Rosiane Aparecida Miranda ,
Maria Lucia Bonfleur ,
Sandra Lucinei Balbo ,
Alex Christian Manhães ,
Elaine Oliveira ,
Egberto Gaspar de Moura Open the ORCID record for Egberto Gaspar de Moura [Opens in a new window]  and
Patricia Cristina Lisboa Open the ORCID record for Patricia Cristina Lisboa [Opens in a new window]
Iala Milene Bertasso
Affiliation:
Laboratory of Endocrine Physiology, Biology Institute, State University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil
Carla Bruna Pietrobon
Affiliation:
Laboratory of Endocrine Physiology, Biology Institute, State University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil
Beatriz Souza da Silva
Affiliation:
Laboratory of Endocrine Physiology, Biology Institute, State University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil
Rosiane Aparecida Miranda
Affiliation:
Laboratory of Endocrine Physiology, Biology Institute, State University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil
Maria Lucia Bonfleur
Affiliation:
Laboratory of Endocrine Physiology and Metabolism, Center of Biological and Health Sciences, Western Paraná State University, Cascavel, PR, Brazil
Sandra Lucinei Balbo
Affiliation:
Laboratory of Endocrine Physiology and Metabolism, Center of Biological and Health Sciences, Western Paraná State University, Cascavel, PR, Brazil
Alex Christian Manhães
Affiliation:
Laboratory of Neurophysiology, Biology Institute, State University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil
Elaine Oliveira
Affiliation:
Laboratory of Endocrine Physiology, Biology Institute, State University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil
Egberto Gaspar de Moura
Affiliation:
Laboratory of Endocrine Physiology, Biology Institute, State University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil
Patricia Cristina Lisboa*
Affiliation:
Laboratory of Endocrine Physiology, Biology Institute, State University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil
*
Address for correspondence: Patricia Cristina Lisboa, Departamento de Ciências Fisiológicas – 5° and ar, Instituto de Biologia – Universidade do Estado do Rio de Janeiro, Av. 28 de Setembro, 87 – Rio de Janeiro, RJ20551-031, Brazil. Emails: [email protected]; [email protected]
Get access Rights & Permissions [Opens in a new window]

Abstract

Non-pharmacological early weaning (NPEW) induces liver damage in male progeny at adulthood; however, pharmacological early weaning (PEW) does not cause this dysfunction. To elucidate this difference in liver dysfunction between these two models and determine the phenotype of female offspring, de novo lipogenesis, β-oxidation, very low-density lipoprotein (VLDL) export, and gluconeogenesis in both sexes were investigated in the adult Wistar rats that were weaned after a normal period of lactation (control group) or early weaned either by restriction of access to the dams’ teats (NPEW group) or by reduction of dams’ milk production with bromocriptine (PEW group). The offspring received standard diet from weaning to euthanasia (PN180). NPEW males had higher plasma triglycerides and TyG index, liver triglycerides, and cholesterol by de novo lipogenesis, which leads to intracellular lipids accumulation. As expected, hepatic morphology was preserved in PEW males, but they showed increased liver triglycerides. The only molecular difference between PEW and NPEW males was in acetyl-CoA carboxylase-1 (ACC-1) and stearoyl-CoA desaturase-1 (SCD-1), which were lower in PEW animals. Both early weaning (EW) females had no changes in liver cholesterol and triglyceride contents, and the hepatic cytoarchitecture was preserved. The expression of microsomal triglyceride transfer protein was increased in both the female EW groups, which could constitute a protective factor. The changes in hepatic lipid metabolism in EW offspring were less marked in females. EW impacted in the hepatic cytoarchitecture only in NPEW males, which showed higher ACC-1 and SCD-1 when compared to the PEW group. As these enzymes are lipogenic, it could explain a worsened liver function in NPEW males.

Keywords

Metabolic programmingBreastfeedingBromocriptineSteatosis
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 11 , Issue 5 , October 2020 , pp. 499 - 508
Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2020

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

Berlanga, A, Guiu-Jurado, E, Porras, JA, et al.Molecular pathways in non-alcoholic fatty liver disease. Clin Exp Gastroenterol. 2014; 7, 221–239.Google ScholarPubMed
Brunt, EM.Histopathology of non-alcoholic fatty liver disease. Clin Liver Dis. 2009; 13, 533–544.10.1016/j.cld.2009.07.008CrossRefGoogle ScholarPubMed
Anstee, QM, Goldin, RD.Mouse models in non-alcoholic fatty liver disease and steatohepatitis research. Int J Exp Path. 2006; 87, 1–16.10.1111/j.0959-9673.2006.00465.xCrossRefGoogle ScholarPubMed
Geisler, CE, Renquist, BJ.Hepatic lipid accumulation: cause and consequence of dysregulated glucoregulatory hormones. J Endocrinol. 2017; 234, 1–21.10.1530/JOE-16-0513CrossRefGoogle ScholarPubMed
Day, CP, James, OF.Steatohepatitis: a tale of two ‘hits’? Gastroenterology. 1998; 114, 842–845.CrossRefGoogle Scholar
Angulo, P.Nonalcoholic fatty liver disease. N Engl J Med. 2002; 346, 1221–1231.CrossRefGoogle ScholarPubMed
Sass, DA, Chang, P, Chopra, KB.Nonalcoholic fatty liver disease: a clinical review. Dig Dis Sci. 2005; 50, 171–180.CrossRefGoogle ScholarPubMed
Chalasani, N, Younossi, Z, Lavine, JE, et al.The diagnosis and management of non-alcoholic fatty liver disease: practice guideline by the American association for the study of liver diseases, American college of gastroenterology, and the American gastroenterological association. Hepatology. 2012; 55, 2005–2023.10.1002/hep.25762CrossRefGoogle Scholar
Zambrano, E, Ibanez, C, Martinez-Samayoa, PM, et al.Maternal obesity: lifelong metabolic outcomes for offspring from poor developmental trajectories during the perinatal period. Arch Med Res. 2016; 47, 1–12.10.1016/j.arcmed.2016.01.004CrossRefGoogle ScholarPubMed
Barker, DJ.The developmental origins of chronic adult disease. Acta Paediatr Suppl. 2004; 446, 26–33.Google Scholar
De Moura, EG, Lisboa, PC, Passos, MC.Neonatal programming of neuroimmunomodulation – role of adipocytokines and neuropeptides. Neuroimmunomodulation. 2008; 15, 176–188.CrossRefGoogle ScholarPubMed
Haugen, AC, Schug, TT, Collman, G, et al.Evolution of DOHaD: the impact of environmental health sciences. J Dev Orig Health Dis. 2015; 6, 55–64.10.1017/S2040174414000580CrossRefGoogle ScholarPubMed
Victora, CG, Bahl, R, Barros, AJD, et al. Breastfeeding in the 21st century: epidemiology, mechanisms, and lifelong effect. Lancet. 2016; 387, 475–490.Google Scholar
Horta, BL, Victora, CG, Franca, GVA, et al.Breastfeeding moderates FTO related adiposity: a birth cohort study with 30 years of follow-up. Sci Rep. 2018; 8, 1–11.10.1038/s41598-018-20939-4CrossRefGoogle ScholarPubMed
Bonomo, IT, Lisboa, PC, Pereira, AR, et al.Prolactin inhibition in dams during lactation programs for overweight and leptin resistance in adult offspring. J Endocrinol. 2007; 192, 339–344.10.1677/joe.1.06952CrossRefGoogle ScholarPubMed
De Moura, EG, Bonomo, IT, Nogueira-Neto, JF, et al.Maternal prolactin inhibition during lactation programs for metabolic syndrome in adult progeny. J Physiol. 2009; 587, 4919–4929.10.1113/jphysiol.2009.176289CrossRefGoogle ScholarPubMed
Lima, NS, Moura, EG, Passos, MCF, et al.Early weaning causes undernutrition for a short period and programmes some metabolic syndrome components and leptin resistance in adult rat offspring. Br J Nutr. 2011; 105, 1405–1413.10.1017/S0007114510005064CrossRefGoogle Scholar
Nobre, JL, Lisboa, PC, Lima, NS, et al.Calcium supplementation prevents obesity, hyperleptinaemia and hyperglycaemia in adult rats programmed by early weaning. Br J Nutr. 2012; 107, 979–988.CrossRefGoogle ScholarPubMed
Quinn, R.Comparing rat’s to human’s age: how old is my rat in people years? Nutrition. 2005; 21, 775–777.10.1016/j.nut.2005.04.002CrossRefGoogle ScholarPubMed
Bonomo, IT, Lisboa, PC, Passos, MC, et al.Prolactin inhibition in lactating rats changes leptin transfer through the milk. Horm Metab Res. 2005; 37, 220–225.10.1055/s-2005-861381CrossRefGoogle ScholarPubMed
Franco, JG, Lisboa, PC, Lima, NS, et al.Resveratrol attenuates oxidative stress and prevents steatosis and hypertension in obese rats programmed by early weaning. J Nutr Biochem. 2013; 24, 960–966.10.1016/j.jnutbio.2012.06.019CrossRefGoogle ScholarPubMed
Peixoto-Silva, N, Conceição, EPS, Carvalho, JC, et al.Does bromocriptine play a role in decreasing oxidative stress for early weaned programmed obesity? Life Sci. 2014; 95, 14–21.CrossRefGoogle ScholarPubMed
Davis, LM, Pei, Z, Trush, MA, et al.Bromocriptine reduces steatosis in obese rodent model. J Hepatol. 2006; 45, 439–444.CrossRefGoogle Scholar
Lima, NS, Moura, EG, Franco, JG, et al.Developmental plasticity of endocrine disorders in obesity model primed by early weaning in dams. Horm Metab Res. 2013; 45, 22–30.Google ScholarPubMed
Bigazzi, M, Ronga, R, Lancranjan, I, et al.A pregnancy in an acromegalic woman during bromocriptine treatment: effects on growth hormone and prolactin in the maternal, fetal and amniotic compartments. J Clin Endocrinol Metab. 1979; 48, 9–12.CrossRefGoogle Scholar
Zhang, Z, Cheng, W.Management of pituitary adenoma in pregnancy. Zhonghua Fu Chan Ke Za Zhi. 1996; 3, 537–539.Google Scholar
Bonomo, IT, Lisboa, PC, Passos, MCF, et al.Prolactin inhibition at the end of lactation programs for a central hypothyroidism in adult rat. J endocrinol. 2008; 198, 331–338.CrossRefGoogle ScholarPubMed
Peixoto‐Silva, N, Moura, EG, Carvalho, JC, et al. (2017). Bromocriptine treatment at the end of lactation prevents hyperphagia, higher visceral fat and liver triglycerides in early-weaned rats at adulthood. Clin Exp Pharmacol Physiol. 2017; 44, 488–499.CrossRefGoogle ScholarPubMed
De Albuquerque Maia, L, Lisboa, PC, de Oliveira, E, et al.Bone metabolism in obese rats programmed by early weaning. Metabolism. 2014; 63, 352–364.CrossRefGoogle ScholarPubMed
Frankenfeld, SP, De Oliveira, LP, Ignacio, DL, et al.Nandrolone decanoate inhibits gluconeogenesis and decreases fasting glucose in Wistar male rats. J Endocrinol. 2014; 220, 143–153.CrossRefGoogle ScholarPubMed
Folch, J, Lees, M, Sloane Stanley, GH.A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem. 1957; 226, 497–509.Google Scholar
Guerrero-Romero, F, Simental-Mendía, LE, González-Ortiz, M, et al.The product of triglycerides and glucose, a simple measure of insulin sensitivity. Comparison with the euglycemic-hyperinsulinemic clamp. J Clin Endocrinol Metab. 2010; 95, 3347–3351.CrossRefGoogle ScholarPubMed
Catta-Preta, M., Mendonca, LS, Fraulob-Aquino, J, Aguila, MB, Mandarim-de-Lacerda CA. A critical analysis of three quantitative methods of assessment of hepatic steatosis in liver biopsies. Virchows Archiv. 2011; 459, 477–485.CrossRefGoogle ScholarPubMed
Brunt, EM.Nonalcoholic steatohepatitis: definition and pathology. Sem in Liv Dis. 2001; 21, 3–16.CrossRefGoogle ScholarPubMed
Huynh, H, Feldt, LS.Estimation of the Box correction for degrees of freedom from the sample data in randomized block and split-plot designs. J Educ Stat. 1976; 1, 69–82.10.3102/10769986001001069CrossRefGoogle Scholar
Snedecor, GW, Cochran, WG.Statistical Methods. 6th ed. Ames, 1967; pp. 593. Iowa State University Press, Iowa, USA.Google Scholar
Pietrobon, CB, Bertasso, IM, Silva, BS, et al.Body adiposity and endocrine profile of female Wistar rats of distinct ages that were early weaned. Horm Metab Res. 2020; 52, 58–66.Google ScholarPubMed
Pietrobon, CB, Miranda, RA, Bertasso, IM, et al.Early weaning induces short-and long-term effects on pancreatic islets in Wistar rats of both sexes. J Physiol. 2020; 598, 489–502.CrossRefGoogle ScholarPubMed
Jornayvaz, FR, Samuel, VT, Shulman, GI.The role of muscle insulin resistance in the pathogenesis of atherogenic dyslipidemia and nonalcoholic fatty liver disease associated with the metabolic syndrome. Annu Ver Nutr. 2010; 30, 273–290.CrossRefGoogle ScholarPubMed
Jiang, T, Zhang, Y, Bai, M, et al.Up-regulation of hepatic fatty acid transporters and inhibition/down-regulation of hepatic OCTN2 contribute to olanzapine-induced liver steatosis. Toxicol Lett. 2019; 316, 183–193.CrossRefGoogle ScholarPubMed
Ikonen, E.Cellular cholesterol trafficking and compartmentalization. Nat Rev Mol Cell Biol. 2008; 9, 125–138.CrossRefGoogle ScholarPubMed
Pownall, HJ, Gotto, AM. Jr Cholesterol: can’t live with it, can’t live without it. Methodist DeBakey Cardiovasc J. 2019; 15, 9–15.Google Scholar
Browning, JD, Szczepaniak, LS, Dobbins, R, et al.Prevalence of hepatic steatosis in an urban population in the United States: Impact of ethnicity. Hepatology. 2004; 40, 1387–1395.CrossRefGoogle Scholar
Clark, JM.Weight loss as a treatment for nonalcoholic fatty liver disease. J Clin Gastroenterol. 2006; 40, 39–43.Google ScholarPubMed
Volzke, H, Schwarz, S, Baumeister, SE, et al.Menopausal status and hepatic steatosis in a general female population. Gut. 2007; 56, 594–595.10.1136/gut.2006.115345CrossRefGoogle Scholar
Polyzos, SA, Kountouras, J, Tsatsoulis, A, et al.Sex steroids and sex hormone-binding globulin in postmenopausal women with nonalcoholic fatty liver disease. Hormones. 2013; 12, 405–416.CrossRefGoogle ScholarPubMed
Lee, YH, Kim, SH, Kim, SN, et al.Sex-specific metabolic interactions between liver and adipose tissue in MCD diet-induced nonalcoholic fatty liver disease. Oncotarget. 2016; 7, 46959–46971.CrossRefGoogle Scholar
Gruber, CJ, Tschugguel, W, Schneeberger, C, et al.Production and actions of estrogens. N Engl J Med. 2002; 346, 340–352.10.1056/NEJMra000471CrossRefGoogle ScholarPubMed
Jia, M, Dahlman-Wright, K, Gustafsson, JÅ.Estrogen receptor alpha and beta in health and disease. Best Pract Res Clin Endocrinol Metab. 2015; 29, 557–568.CrossRefGoogle ScholarPubMed
Nilsson, S, Makela, S, Treuter, E, et al.Mechanisms of estrogen action. Physiol Rev. 2001; 81, 1535–1565.10.1152/physrev.2001.81.4.1535CrossRefGoogle ScholarPubMed
Hevener, AL, Clegg, DJ, Mauvais-Jarvis, F.Impaired estrogen receptor action in the pathogenesis of the metabolic syndrome. Mol Cell Endocrinol. 2015, 418, 306–321.CrossRefGoogle ScholarPubMed
Rettberg, JR, Yao, J, Brinton, RD.Estrogen: a master regulator of bioenergetic systems in the brain and body. Front Neuroendocrinol. 2014; 35, 8–30.CrossRefGoogle ScholarPubMed
Morselli, E, Santos, RS, Criollo, A, et al.The effects of oestrogens and their receptors on cardiometabolic health. Nat Rev Endocrinol. 2017; 13, 352–364.CrossRefGoogle ScholarPubMed
Shimizu, T, Yu, HP, Suzuki, T, et al.The role of estrogen receptor subtypes in ameliorating hepatic injury following trauma-hemorrhage. J Hepatol. 2007; 46, 1047–1054.CrossRefGoogle ScholarPubMed
Barsalani, R, Chapados, NA, Lavoie, JM.Hepatic VLDL-TG production and MTP gene expression are decreased in ovariectomized rats: effects of exercise training. Horm Metab Res. 2010; 42, 860–867.CrossRefGoogle ScholarPubMed
D’Eon, TM, Souza, SC, Aronovitz, M, et al.Estrogen regulation of adiposity and fuel partitioning evidence of genomic and non-genomic regulation of lipogenic and oxidative pathways. J Biol Chem. 2005; 280, 35983–35991.CrossRefGoogle ScholarPubMed
Paquette, A, Wang, D, Jankowski, M, et al.Effects of ovariectomy on PPARα, SREBP-1c, and SCD-1 gene expression in the rat liver. Menopause. 2008; 15, 1169–1175.CrossRefGoogle ScholarPubMed
Paquette, A, Chapados, NA, Bergeron, R, et al.Fatty acid oxidation is decreased in the liver of ovariectomized rats. Horm Metab Res. 2009; 41, 511–515.CrossRefGoogle ScholarPubMed
Chen, J, Yue, J, Liu, Y, et al.Blocking of STAT-3/SREBP1-mediated glucose–lipid metabolism is involved in dietary phytoestrogen-inhibited ovariectomized-induced body weight gain in rats. J Nutr Biochem. 2018; 61, 17–23.CrossRefGoogle ScholarPubMed
Guillaume, M, Handgraaf, S, Fabre, A, et al.Selective activation of estrogen receptor α activation Function-1 is sufficient to prevent obesity, steatosis, and insulin resistance in mouse. American J Pathol. 2017; 187, 1273–1287.CrossRefGoogle Scholar
Kamada, Y, Kiso, S, Yoshida, Y, et al.Estrogen deficiency worsens steatohepatitis in mice fed high fat and high cholesterol diet. Am J Physiol Gastrointest Liver Physiol. 2011; 301, 1031–1043.10.1152/ajpgi.00211.2011CrossRefGoogle ScholarPubMed
Gao, H, Bryzgalova, G, Hedman, E, et al.Long-term administration of estradiol decreases expression of hepatic lipogenic genes and improves insulin sensitivity in ob/ob mice: a possible mechanism is through direct regulation of signal transducer and activator of transcription 3. Mol Endocrinol. 2006; 20, 1287–1299.CrossRefGoogle ScholarPubMed
Chukijrungroat, N, Khamphaya, T, Weerachayaphorn, J, et al.Hepatic FGF21 mediates gender differences in high-fat high-fructose diet induced fatty liver. Am J Physiol Endocrinol Metab. 2017; 313, 203–212.CrossRefGoogle ScholarPubMed
Gibbons, GF, Wiggins, D, Brown, AM, et al.Synthesis and function of hepatic very-low-density lipoprotein. Biochem Soc Trans. 2004; 32, 59–64.CrossRefGoogle ScholarPubMed
Wetterau, JR, Lin, MC, Jamil, H.Microsomal triglyceride transfer protein. Biochim Biophys Acta. 1997; 1345, 136–150.10.1016/S0005-2760(96)00168-3CrossRefGoogle ScholarPubMed
Améen, C, Oscarsson, J.Sex difference in hepatic microsomal triglyceride transfer protein expression is determined by the growth hormone secretory pattern in the rat. Endocrinology. 2003; 144, 3914–3921.CrossRefGoogle ScholarPubMed
Picard, F, Deshaies, Y, Lalonde, J, et al.Effects of the estrogen antagonist EM-652.HCl on energy balance and lipid metabolism in ovariectomized rats. Int J Obes. 2000; 24, 830–840.CrossRefGoogle ScholarPubMed
Supplementary material: Image

Bertasso et al. supplementary material

Bertasso et al. supplementary material

Download Bertasso et al. supplementary material(Image)
Image 3.7 MB