Hitting a triple in the non-alcoholic fatty liver disease field: sucrose intake in adulthood increases fat content in the female but not in the male rat offspring of dams fed a gestational low-protein diet

Abstract

The excessive consumption of carbohydrates is related to non-alcoholic fatty liver disease (NAFLD) in infants and adults. The effect of combining maternal malnutrition and a high carbohydrate intake on the development of NAFLD in adulthood remains unknown. We therefore hypothesized that consumption of 5% sucrose by the offspring of dams fed a low-protein diet during pregnancy promotes liver fat accumulation and oxidative damage differently in females and males. To test this, 12-month-old female and male offspring of mothers fed a Control (C) or low-protein diet (Restricted, R) were provided with either tap water or 5% sucrose for a period of 10 weeks. Livers were excised to measure the fat content and 3-nitrotyrosine (3-NTyr) immunostaining; serum samples were also obtained to measure the concentration of malondialdehyde (MDA). Data were analyzed using a non-repeated measures three-way analysis of variance to determine significant differences (P<0.05) regarding to the interaction among maternal diet, sucrose consumption and sex. Results showed that the liver fat content of females from R mothers was higher than that of their male counterpart. Hepatic 3-NTyr immunostaining and serum MDA concentrations were not affected by the interaction involving maternal diet, sucrose consumption and sex. Otherwise, liver fat content was correlated with the hepatic 3-NTyr immunostaining and serum MDA concentrations only in females. Thus, sucrose intake in adulthood increases fat content in the female but not in the male rat offspring of dams fed with a low-protein diet during pregnancy. This research emphasizes the importance of a balanced diet during pregnancy and the influence of the diet on the adult offspring.

Maternal and Offspring Sugar Consumption Increases Perigonadal Adipose Tissue Hypertrophy and Negatively Affects the Testis Histological Organization in Adult Rats

“…This increase in the sugar consumption is present from gestation (Gamba et al, 2019;Casas et al, 2020) and breastfeeding (Zou et al, 2012), continuing throughout childhood (Dubois et al, 2007;De León-Ramírez et al, 2021) and adult life (Kumar et al, 2014). During gestation and breastfeeding, nutrition through the maternal diet plays a critical role (Cervantes-Rodríguez et al, 2014;Nicolás-Toledo et al, 2018;Pedrana et al, 2020), it is already well known that imbalances in the adequate consumption of macronutrients, such as proteins (Pedrana et al, 2020) and carbohydrates (Casas et al, 2020), negatively affect the development and maturation of different organs in later stages (Cervantes-Rodríguez et al, 2014;Nicolás-Toledo et al, 2018;Corona-Quintanilla et al, Online ahead of print) because both the glucose and fructose cross the placenta (Holmberg et al, 1956) and fetal development depends on transport of glucose through the mother's blood (Regnault et al, 2013). These programmed or established changes during the fetal/ embryonic stage that can cause diseases in adulthood are known as the theory of the origin and development of diseases (Barker, 1990).…”

“…Both high-calorie diets (Jastrzębska et al, 2014;De León-Ramírez et al, 2021) and a BMI > 25 kg/m 2 (overweight and obesity) (Organization for Economic Co-operation and Development (OECD), 2017; Morales et al, 2014) is associated with male reproductive tract diseases related to some metabolic disorders (metabolic syndrome, insulin resistance, and dyslipidemias) (Nicolás-Toledo et al, 2018;De León-Ramírez et al, 2021). In animal models, high-carbohydrate diets have been established depending on the type and amount of mono, di, or polysaccharide used (Rodríguez-Correa et al, 2020).…”

Non-alcoholic fatty liver disease and the impact of genetic, epigenetic and environmental factors in the offspring

“…Therefore, the study concluded that fructose intake during adolescence hastens NAFLD onset and reveals a differentiated hepatic response to metabolic insult, depending on the maternal diet. Notwithstanding, Nicolás-Toledo et al [ 43 ] showed that sucrose intake in adulthood increases fat content only in female rat offspring of dams fed with a low-protein diet during pregnancy, reinforcing the influence of maternal diet in the offspring[ 43 ]. Of note, regarding specific epigenetic mechanisms, Suter et al [ 44 ] have described that epigenetic changes to histones may act as a molecular memory of intrauterine exposure, rendering the risk of adult disease.…”

Bulbospongiosus Muscle Frecuency Activity is Modified by Sucrose Consumption During Pregnancy-lactation and Postweaning Offspring Male Rats

“…2,3 It related metabolic disorders of the progeny with the type of maternal nutrition during the perinatal period (gestation and lactation). [4][5][6][7] A high sucrose diet increased the fat mass and reduced lean mass in the offspring. [8][9][10][11] Likewise, the histological arrangement of the testis is hypertrophied 12 and affects the neural and endothelial components of penile erection.…”

“…18 The regulation adequately promotes the muscle development and homeostasis in coordination with liver and adipose tissue metabolism. 7,18 Alterations in the growth and the development of the skeletal muscle during the perinatal period could result not only in muscle mass defects, besides metabolic disorders 19 that are related with the erectile dysfunction in males. 15,20 An explanation is severe alterations in the pelvic 15 or perineal 21 muscles, which play a role in erectile dysfunction with metabolic disorders.…”