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 in: Journal of developmental origins of health and disease Vol. 13; no. 2; pp. 263 - 273
• Main Authors: Bertasso, Iala Milene, Pietrobon, Carla Bruna, Ribeiro, Rosane Aparecida, Soares, Gabriela Moreira, Oliveira, Janaina Chaves de, Alegre-Maller, Ana Claudia Paiva, Boschero, Antonio Carlos, Araújo, Allan Cezar Faria, Guimarães, Ana Tereza Bittencourt, Bonfleur, Maria Lúcia, Balbo, Sandra Lucinei
• Format: Journal Article
• Language: English
• Published: Cambridge, UK Cambridge University Press 01.04.2022
• Subjects: Abdomen; Adult; Adults; Age; Animals; Breastfeeding & lactation; Diabetes; Diet, High-Fat - adverse effects; Female; Females; Gastric Bypass - adverse effects; Gastrointestinal surgery; Humans; Lactation; Lipids; Lipogenesis; Liver - metabolism; Liver diseases; Male; Metabolism; Mortality; Non-alcoholic Fatty Liver Disease - etiology; Non-alcoholic Fatty Liver Disease - metabolism; Obesity; Obesity - complications; Obesity - surgery; Original Article; Pregnancy; Rats; Rats, Wistar; Rodents; Small intestine; Womens health; maternal programming; non-alcoholic fatty liver disease; pregnancy and lactation; Bariatric operation; obesity
• ISSN: 2040-1744; 2040-1752
• DOI: 10.1017/S2040174421000271

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.