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Pregnancy and lactation after Roux-en-Y gastric bypass worsen nonalcoholic fatty liver disease in obese rats and lead to differential programming of hepatic de novo lipogenesis in offspring

Published online by Cambridge University Press:  17 May 2021

Iala Milene Bertasso
Affiliation:
Laboratório de Fisiologia Endócrina e Metabolismo (LAFEM), Centro de Ciências Biológicas e da Saúde, Universidade Estadual do Oeste do Paraná (UNIOESTE), Cascavel, PR, Brazil
Carla Bruna Pietrobon
Affiliation:
Laboratório de Fisiologia Endócrina e Metabolismo (LAFEM), Centro de Ciências Biológicas e da Saúde, Universidade Estadual do Oeste do Paraná (UNIOESTE), Cascavel, PR, Brazil
Rosane Aparecida Ribeiro
Affiliation:
Departamento de Biologia Geral, Setor de Ciências Biológicas e da Saúde, Universidade Estadual de Ponta Grossa (UEPG), Ponta Grossa, PR, Brazil
Gabriela Moreira Soares
Affiliation:
Laboratório de Pâncreas Endócrino e Metabolismo, Departamento de Biologia Estrutural e Funcional, Instituto de Biologia, Universidade Estadual de Campinas (UNICAMP), Campinas, SP, Brazil
Janaina Chaves de Oliveira
Affiliation:
Laboratório de Fisiopatologia, Divisão de Pesquisa Integrada em Produtos Bioativos e Biociências, Universidade Federal do Rio de Janeiro, Campus UFRJ-Macaé, Macaé, RJ, Brazil
Ana Claudia Paiva Alegre-Maller
Affiliation:
Laboratório de Fisiologia Endócrina e Metabolismo (LAFEM), Centro de Ciências Biológicas e da Saúde, Universidade Estadual do Oeste do Paraná (UNIOESTE), Cascavel, PR, Brazil
Antonio Carlos Boschero
Affiliation:
Laboratório de Pâncreas Endócrino e Metabolismo, Departamento de Biologia Estrutural e Funcional, Instituto de Biologia, Universidade Estadual de Campinas (UNICAMP), Campinas, SP, Brazil
Allan Cezar Faria Araújo
Affiliation:
Centro de Ciências Médicas e Farmacêuticas, UNIOESTE, Cascavel, PR, Brazil
Ana Tereza Bittencourt Guimarães
Affiliation:
Laboratório de Fisiologia Endócrina e Metabolismo (LAFEM), Centro de Ciências Biológicas e da Saúde, Universidade Estadual do Oeste do Paraná (UNIOESTE), Cascavel, PR, Brazil
Maria Lúcia Bonfleur*
Affiliation:
Laboratório de Fisiologia Endócrina e Metabolismo (LAFEM), Centro de Ciências Biológicas e da Saúde, Universidade Estadual do Oeste do Paraná (UNIOESTE), Cascavel, PR, Brazil
Sandra Lucinei Balbo
Affiliation:
Laboratório de Fisiologia Endócrina e Metabolismo (LAFEM), Centro de Ciências Biológicas e da Saúde, Universidade Estadual do Oeste do Paraná (UNIOESTE), Cascavel, PR, Brazil
*
Address for correspondence: Maria Lúcia Bonfleur, Endocrine Physiology and Metabolism Laboratory, Cascavel, PR, Brazil, Zip code: 858119-110. Email: [email protected]

Abstract

Maternal obesity increases the risk of nonalcoholic fatty liver disease (NAFLD) in offspring. The Roux-en-Y gastric bypass (RYBG) is effective for achieving weight loss and ameliorates NAFLD. To determine whether these benefits are maintained after pregnancy and/or lactation, and whether they modulate hepatic morphofunction in the next generation, we evaluated hepatic lipid metabolism in Western diet (WD)-obese female rats that underwent RYGB and in their F1 offspring at adulthood. Female Wistar rats consumed a WD from 21 to 130 days of age, before being submitted to RYGB (WD-RYGB-F0) or SHAM (WD-SHAM-F0) operations. After 5 weeks, these females were mated with control male breeders, and the male and female F1 offspring were identified as WD-RYGB-F1 and WD-SHAM-F1. WD-RYGB-F0 dams exhibited lower serum lipids levels, but severe hepatic steatosis and pathological features of advanced liver injury. The hepatic proteins involved in lipogenesis were reduced in WD-RYGB-F0, as were the genes related to β-oxidation and bile acids (BAs). Although the female and male WD-RYGB-F1 groups did not exhibit hepatic steatosis, the livers of female WD-RYGB-F1 demonstrated higher amounts of lipogenic genes and proteins, while male WD-RYGB-F1 presented a similar downregulation of lipogenic factors to that seen in WD-RYGB-F0 dams. In contrast, maternal and offspring groups of both sexes displayed reductions in the expressions of genes involved in BAs physiology and gluconeogenesis. As such, RYGB aggravates NAFLD after pregnancy and lactation and induces a gender-dependent differential expression of the hepatic lipogenesis pathway in offspring, indicating that female WD-RYGB-F1 may be an increased risk of developing NAFLD.

Type
Original Article
Copyright
© The Author(s), 2021. Published by Cambridge University Press in association with International Society for Developmental Origins of Health and Disease

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References

Silvestris, E, de Pergola, G, Rosania, R, Loverro, G. Obesity as disruptor of the female fertility. Reprod Biol Endocrinol. 2018; 16, 22.CrossRefGoogle ScholarPubMed
Scott-Pillai, R, Spence, D, Cardwell, CR, Hunter, A, Holmes, VA. The impact of body mass index on maternal and neonatal outcomes: a retrospective study in a UK obstetric population, 2004–2011. BJOG. 2013; 120, 932939.CrossRefGoogle Scholar
Khan, MN, Rahman, MM, Shariff, AA, et al. Maternal undernutrition and excessive body weight and risk of birth and health outcomes. Arch Public Health. 2017; 75, 12.CrossRefGoogle ScholarPubMed
Dahlhoff, M, Pfister, S, Blutke, A, et al. Peri-conceptional obesogenic exposure induces sex-specific programming of disease susceptibilities in adult mouse offspring. Biochim Biophys Acta. 2014; 1842, 304317.CrossRefGoogle ScholarPubMed
Hanafi, MY, Saad, MI, Abdelkhalek, TM, Saleh, MM, Kamel, MA. In utero nutritional manipulation provokes dysregulated adipocytokines production in F1 offspring in rats. Scientifica (Cairo). 2016; 2016, 3892890.Google ScholarPubMed
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, 112.CrossRefGoogle ScholarPubMed
Wankhade, UD, Zhong, Y, Kang, P, et al. Maternal high-fat diet programs offspring liver steatosis in a sexually dimorphic manner in association with changes in gut microbial ecology in mice. Sci Rep. 2018; 8, 16502.CrossRefGoogle Scholar
Lomas-Soria, C, Reyes-Castro, LA, Rodriguez-Gonzalez, GL, et al. Maternal obesity has sex-dependent effects on insulin, glucose and lipid metabolism and the liver transcriptome in young adult rat offspring. J Physiol. 2018; 596, 46114628.CrossRefGoogle ScholarPubMed
Contos, MJ, Choudhury, J, Mills, AS, Sanyal, AJ. The histologic spectrum of nonalcoholic fatty liver disease. Clin Liver Dis. 2004; 8, 481500.CrossRefGoogle ScholarPubMed
Younossi, ZM, Koenig, AB, Abdelatif, D, et al. Global epidemiology of nonalcoholic fatty liver disease-meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2016; 64, 7384.CrossRefGoogle ScholarPubMed
Donnelly, KL, Smith, CI, Schwarzenberg, SJ, et al. Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease. J Clin Invest. 2005; 115, 13431351.CrossRefGoogle ScholarPubMed
Fujita, K, Imajo, K, Shinohara, Y, et al. Novel findings for the development of drug therapy for various liver diseases: liver microsomal triglyceride transfer protein activator may be a possible therapeutic agent in non-alcoholic steatohepatitis. J Pharmacol Sci. 2011; 115, 270273.CrossRefGoogle ScholarPubMed
Koo, SH. Nonalcoholic fatty liver disease: molecular mechanisms for the hepatic steatosis. Clin Mol Hepatol. 2013; 19, 210215.CrossRefGoogle ScholarPubMed
Berlanga, A, Guiu-Jurado, E, Porras, JA, Auguet, T. Molecular pathways in non-alcoholic fatty liver disease. Clin Exp Gastroenterol. 2014; 7, 221239.Google ScholarPubMed
Sampey, BP, Vanhoose, AM, Winfield, HM, et al. Cafeteria diet is a robust model of human metabolic syndrome with liver and adipose inflammation: comparison to high-fat diet. Obesity. 2011; 19, 11091117.CrossRefGoogle ScholarPubMed
Balbo, SL, Ribeiro, RA, Mendes, MC, et al. Vagotomy diminishes obesity in cafeteria rats by decreasing cholinergic potentiation of insulin release. J Physiol Biochem. 2016; 72, 625633.CrossRefGoogle ScholarPubMed
Gloy, VL, Briel, M, Bhatt, DL et al. Bariatric surgery versus non-surgical treatment for obesity: a systematic review and meta-analysis of randomised controlled trials. BMJ. 2013; 347, f5934.CrossRefGoogle ScholarPubMed
Cheng, J, Gao, J, Shuai, X, Wang, G, Tao, K. The comprehensive summary of surgical versus non-surgical treatment for obesity: a systematic review and meta-analysis of randomized controlled trials. Oncotarget. 2016; 7, 3921639230.CrossRefGoogle ScholarPubMed
Browning, MG, Pessoa, BM, Khoraki, J, Campos, GM. Changes in bile acid metabolism, transport, and signaling as central drivers for metabolic improvements after bariatric surgery. Curr Obes Rep 2019; 8; 175184.CrossRefGoogle ScholarPubMed
Cummings, BP, Graham, JL, Stanhope, KL, Chouinard, ML, Havel, PJ. Maternal ileal interposition surgery confers metabolic improvements to offspring independent of effects on maternal body weight in UCD-T2DM rats. Obes Surg. 2013; 23, 20422049.CrossRefGoogle ScholarPubMed
Grayson, BE, Schneider, KM, Woods, SC, Seeley, RJ. Improved rodent maternal metabolism but reduced intrauterine growth after vertical sleeve gastrectomy. Sci Transl Med. 2013; 5, 199ra112.CrossRefGoogle ScholarPubMed
Pietrobon, CB, Bertasso, IM, Ribeiro, RA, et al. Maternal Roux-en-Y gastric bypass impairs insulin action and endocrine pancreatic function in male F1 offspring. Eur J Nutr. 2020; 59, 10671079.CrossRefGoogle ScholarPubMed
Edison, E, Whyte, M, van Vlymen, J, et al. Bariatric surgery in obese women of reproductive age improves conditions that underlie fertility and pregnancy outcomes: Retrospective Cohort Study of UK National Bariatric Surgery Registry (NBSR). Ob Surg. 2016; 26, 28372842.CrossRefGoogle Scholar
Soares, JM Junior, Lobel, A, Ejzenberg, D, Serafini, PC, Baracat, EC. Bariatric surgery in infertile women with morbid obesity: definitive solution? Rev Assoc Med Bras (1992). 2018; 64, 565567.CrossRefGoogle Scholar
Gonzalez, I, Lecube, A, Rubio, MA, Garcia-Luna, PP. Pregnancy after bariatric surgery: improving outcomes for mother and child. Int J Womens Health. 2016; 8, 721729.CrossRefGoogle ScholarPubMed
Machado, SN, Pereira, S, Saboya, C, Saunders, C, Ramalho, A. Influence of Roux-en-Y gastric bypass on the nutritional status of vitamin A in pregnant women: a comparative study. Obes Surg. 2016; 26, 2631.CrossRefGoogle ScholarPubMed
Pan, Q, Qin, T, Gao, Y, et al. Hepatic mTOR-AKT2-Insig2 signaling pathway contributes to the improvement of hepatic steatosis after Roux-en-Y Gastric Bypass in mice. Biochim Biophys Acta Mol Basis Dis. 2019; 1865, 525534.CrossRefGoogle Scholar
Mathes, CM, Letourneau, C, Blonde, GD, le Roux, CW, Spector, AC. Roux-en-Y gastric bypass in rats progressively decreases the proportion of fat calories selected from a palatable cafeteria diet. Am J Physiol Regul Integr Comp Physiol. 2016; 310, 952959.CrossRefGoogle ScholarPubMed
Carswell, KA, Belgaumkar, AP, Amiel, SA, Patel, AG. A systematic review and meta-analysis of the effect of gastric bypass surgery on plasma lipid levels. Obes Surg. 2016; 26, 843855.CrossRefGoogle ScholarPubMed
Flynn, CR, Albaugh, VL, Cai, S, et al. Bile diversion to the distal small intestine has comparable metabolic benefits to bariatric surgery. Nat Commun. 2015; 6, 7715.CrossRefGoogle Scholar
Pihlajamäki, J, Grönlund, S, Simonen, M, et al. Cholesterol absorption decreases after Roux-en-Y gastric bypass but not after gastric banding. Metab Clin Exp. 2010; 59, 866872.CrossRefGoogle Scholar
Kalinowski, P, Paluszkiewicz, R, Ziarkiewicz-Wroblewska, B, et al. Liver function in patients with nonalcoholic fatty liver disease randomized to Roux-en-Y gastric bypass versus sleeve gastrectomy: a secondary analysis of a randomized clinical trial. Ann Surg. 2017; 266, 738745.CrossRefGoogle ScholarPubMed
Schwenger, KJP, Fischer, SE, Jackson, T, Okrainec, A, Allard, JP. In nonalcoholic fatty liver disease, Roux-en-Y gastric bypass improves liver histology while persistent disease is associated with lower improvements in waist circumference and glycemic control. Surg Obes Relat Dis. 2018; 14, 12331239.CrossRefGoogle ScholarPubMed
Silva-Morita, FS, Ribeiro, RA, Balbo, SL, et al. Roux-en-Y gastric bypass is more effective than sleeve gastrectomy against hepatic steatosis, in western-diet-obese rats. IJDR. 2018; 8, 2161521621.Google Scholar
Mahawar, KK, Parmar, C, Graham, Y, et al. Monitoring of liver function tests after Roux-en-Y gastric bypass: an examination of evidence base. Obes Surg. 2016; 26, 25162522.CrossRefGoogle ScholarPubMed
Jacobsen, SH, Bojsen-Moller, KN, Dirksen, C, et al. Effects of gastric bypass surgery on glucose absorption and metabolism during a mixed meal in glucose-tolerant individuals. Diabetologia. 2013; 56, 22502254.CrossRefGoogle ScholarPubMed
Verna, EC, Berk, PD. Role of fatty acids in the pathogenesis of obesity and fatty liver: impact of bariatric surgery. Semin Liver Dis. 2008; 28, 407426.CrossRefGoogle ScholarPubMed
Aitchison, RE, Clegg, RA, Vernon, RG. Lipolysis in rat adipocytes during pregnancy and lactation. The response to noradrenaline. Biochem J. 1982; 202, 243247.CrossRefGoogle ScholarPubMed
Pujol, E, Proenza, A, Llado, I, Roca, P. Pregnancy effects on rat adipose tissue lipolytic capacity are dependent on anatomical location. Cell Physiol Biochem. 2005; 16, 229236.CrossRefGoogle ScholarPubMed
Bessone, F, Razori, MV, Roma, MG. Molecular pathways of nonalcoholic fatty liver disease development and progression. Cell Mol Life Sci. 2019; 76, 99128.CrossRefGoogle ScholarPubMed
Basaranoglu, M, Basaranoglu, G, Senturk, H. From fatty liver to fibrosis: a tale of “second hit”. World J Gastroenterol. 2013; 19, 11581165.CrossRefGoogle ScholarPubMed
Risstad, H, Kristinsson, JA, Fagerland, MW, et al. Bile acid profiles over 5 years after gastric bypass and duodenal switch: results from a randomized clinical trial. Surg Obes Relat Dis. 2017; 13, 15441553.CrossRefGoogle ScholarPubMed
de Siqueira Cardinelli, C, Torrinhas, RS, Sala, P, et al. Fecal bile acid profile after Roux-en-Y gastric bypass and its association with the remission of type 2 diabetes in obese women: a preliminary study. Clin Nutr. 2019; 38, 29062912.CrossRefGoogle ScholarPubMed
Gardes, C, Chaput, E, Staempfli, A, et al. Differential regulation of bile acid and cholesterol metabolism by the farnesoid X receptor in Ldlr -/- mice versus hamsters. J Lipid Res. 2013; 54, 12831299.CrossRefGoogle Scholar
Jiao, Y, Lu, Y, Li, XY. Farnesoid X receptor: a master regulator of hepatic triglyceride and glucose homeostasis. Acta Pharmacol Sin. 2015; 36, 4450.CrossRefGoogle ScholarPubMed
Decker, GA, Swain, JM, Crowell, MD, Scolapio, JS. Gastrointestinal and nutritional complications after bariatric surgery. Am J Gastroenterol. 2007; 102, 25712580.CrossRefGoogle ScholarPubMed
Blume, CA, Machado, BM, da Rosa, RR, et al. Association of maternal Roux-en-Y gastric bypass with obstetric outcomes and fluid intelligence in offspring. Obes Surg. 2018; 28, 36113620.CrossRefGoogle ScholarPubMed
Hagstrom, H, Hoijer, J, Ludvigsson, JF, et al. Adverse outcomes of pregnancy in women with non-alcoholic fatty liver disease. Liver Int. 2016; 36, 268274.CrossRefGoogle ScholarPubMed
Thompson, MD, Derse, A, Ferey, J, et al. Transgenerational impact of maternal obesogenic diet on offspring bile acid homeostasis and nonalcoholic fatty liver disease. Am J Physiol Endocrinol Metab. 2019; 316, 674686.CrossRefGoogle ScholarPubMed
Glastras, SJ, Wong, MG, Chen, H, et al. FXR expression is associated with dysregulated glucose and lipid levels in the offspring kidney induced by maternal obesity. Nutr Metab (Lond). 2015; 12, 40.CrossRefGoogle ScholarPubMed
Guenard, F, Deshaies, Y, Cianflone, K, et al. Differential methylation in glucoregulatory genes of offspring born before vs. after maternal gastrointestinal bypass surgery. Proc Natl Acad Sci USA. 2013; 110, 1143911444.CrossRefGoogle ScholarPubMed
Benatti, RO, Melo, AM, Borges, FO, et al. Maternal high-fat diet consumption modulates hepatic lipid metabolism and microRNA-122 (miR-122) and microRNA-370 (miR-370) expression in offspring. Br J Nutr. 2014; 111, 21122122.CrossRefGoogle ScholarPubMed
Wankhade, UD, Zhong, Y, Kang, P, et al. Enhanced offspring predisposition to steatohepatitis with maternal high-fat diet is associated with epigenetic and microbiome alterations. PLoS One. 2017; 12, e0175675.CrossRefGoogle ScholarPubMed
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