Maternal dietary free or bound fructose diversely influence developmental programming of lipogenesis

Abstract

Background: Maternal dietary choices throughout preconception, pregnancy, and lactation irreversibly affect the development of fetal tissues and organs, known as fetal programming. Recommendations tend to emphasize reducing added sugars. However, the impact of maternal dietary free or bound fructose in added sugars on developmental programming of lipogenesis is unknown.

Methods: Virgin Sprague-Dawley rats were randomly divided into five groups. Rats were given feed and plain water (control) or water containing maltodextrin (vehicle), fructose, high-fructose corn syrup (HFCS) containing 55% fructose, sucrose (20% w/v) for 12 weeks before mating and throughout the pregnancy and lactation periods. Body weight, water, and feed intake were measured throughout the study. At the end of the lactation period, blood was drawn to determine the fasting levels of glucose, insulin, triglycerides, and non-esterified fatty acids (NEFA) in blood. Triglycerides and acetyl Co-A Carboxylase-1 (ACC1) levels in livers were analyzed, and insulin resistance was calculated.

Results: The energy intake of dams in the HFCS group was higher than in the fructose group, while weight gain was less in the HFCS group than in the fructose group. HFCS resulted in greater insulin resistance in dams, whereas free fructose had a robust effect on the fetal programming of insulin resistance. Free fructose and HFCS in the maternal diet increased blood and liver triglycerides and NEFA content in pups. Furthermore, fructose and HFCS exposure increased phosphorylated ACC1 as compared to maltodextrin and control, indicating greater fatty acid synthesis in pups and dams.

Conclusion: Different types of added sugar in the maternal diet have different metabolic effects on the developmental programming of lipogenesis. Consequently, high fructose intake via processed foods may increase the risk for chronic diseases, and free fructose might contribute to developmental programming of chronic diseases more than bound fructose.

Keywords: Fetal programming; Fructose; Insulin; Non-esterified fatty acids; Triglyceride.

Fig. 1

Schematic representation of the study design. Plain water (Control), and water with added maltodextrin (Vehicle: Maltodextrin), fructose (Fructose), high fructose corn syrup (HFCS), and sucrose (Sucrose). Values for “n” on the left represent the number of dams and “n” at the bottom represents the total number of offspring chosen

Fig. 2

Effect of dietary free or bound fructose on maternal feed and water intake, and body weight changes of dams and pups. a Body weights of dams during the study; b Daily feed intake of dams during the study; c Daily intake of water with added sugar or plain water of dams during the study; d Birth weights and body weight changes of pups till weaning. Means (nd_ams = 5–7 per group; n_pups = 6–7 per group). *p < 0.05 vs. vehicle (maltodextrin)

Fig. 3

Influence of dietary free or bound fructose on maternal and fetal glucose metabolism and insulin resistance. a Blood glucose levels of dams and pups; b Blood insulin levels of dams and pups; c Blood insulin resistance of dams and pups; d Blood insulin sensitivity of dams and pups. Means ± SEM (n_dams = 5–7 per group; n_pups = 6–7 per group); *p < 0.05 vs. vehicle (maltodextrin); NS, not significant

Fig. 4

Outcome of dietary free or bound fructose on maternal and fetal circulating free fatty acids, triglycerides, and fatty acid synthesis. a Blood triglycerides levels of dams and pups; b Blood non-esterified fatty acids (NEFA) levels of dams and pups; c Liver triglyceride levels of dams and pups; d Acetyl Co-A Carboxylase (ACC1) and phosphorylated forms (p-ACC1) expression estimated by western blot in liver tissue of dams and pups. Means ± SEM (n_dams = 5–7 per group; n_pups = 6–7 per group); *p < 0.05 vs. vehicle (maltodextrin); NS, not significant