Maternal Fructose Intake Causes Developmental Reprogramming of Hepatic Mitochondrial Catalytic Activity and Lipid Metabolism in Weanling and Young Adult Offspring.

Rebecca Maree Dyson,Lifeng Peng,Christina M G Vanderboor,Ousseynou Sarr,Timothy R H Regnault,Erin Vanessa Larae Smith,Clint Gray,Jane Anderson,Mary J Berry

doi:10.3390/ijms23020999

Abstract

Excess dietary fructose is a major public health concern, yet little is known about its influence on offspring development and later-life disease when consumed in excess during pregnancy. To determine whether increased maternal fructose intake could have long-term consequences on offspring health, we investigated the effects of 10% w/v fructose water intake during preconception and pregnancy in guinea pigs. Female Dunkin Hartley guinea pigs were fed a control diet (CD) or fructose diet (FD; providing 16% of total daily caloric intake) ad libitum 60 days prior to mating and throughout gestation. Dietary interventions ceased at day of delivery. Offspring were culled at day 21 (D21) (weaning) and at 4 months (4 M) (young adult). Fetal exposure to excess maternal fructose intake significantly increased male and female triglycerides at D21 and 4 M and circulating palmitoleic acid and total omega-7 through day 0 (D0) to 4 M. Proteomic and functional analysis of significantly differentially expressed proteins revealed that FD offspring (D21 and 4 M) had significantly increased mitochondrial metabolic activities of β-oxidation, electron transport chain (ETC) and oxidative phosphorylation and reactive oxygen species production compared to the CD offspring. Western blotting analysis of both FD offspring validated the increased protein abundances of mitochondrial ETC complex II and IV, SREBP-1c and FAS, whereas VDAC1 expression was higher at D21 but lower at 4 M. We provide evidence demonstrating offspring programmed hepatic mitochondrial metabolism and de novo lipogenesis following excess maternal fructose exposure. These underlying asymptomatic programmed pathways may lead to a predisposition to metabolic dysfunction later in life.

Highlights

Fructose has become a major public health concern due to the associated increase of metabolic diseases such as; dyslipidemia, hyperlipidemia, insulin resistance, visceral adiposity, obesity, diabetes, high blood pressure, cardiovascular disease and non-alcoholic fatty liver disease (NAFLD) [1–7]
fructose diet (FD) males and females had significantly decreased bone mineral density (BMD) compared to control diet (CD) offspring, an effect of diet
FD males and females had significantly decreased BMD compared to CD offspring, an of effect of Maternal diet

Summary

Introduction

Fructose has become a major public health concern due to the associated increase of metabolic diseases such as; dyslipidemia, hyperlipidemia, insulin resistance, visceral adiposity, obesity, diabetes, high blood pressure, cardiovascular disease and non-alcoholic fatty liver disease (NAFLD) [1–7]. When considering the impact of fructose on the prevalence 4.0/). In the presence of readily available hepatic glucose and glycogen stores, key metabolic pathways of fructose metabolism become unregulated and excess fructose is channeled to lipogenesis. The chronic metabolic alteration caused by excess fructose consumption initiates an adaptive series of responses in signaling pathways. These adaptive responses to an abnormal hepatic de novo lipogenesis may contribute to altered mitochondrial catalytic activity and function and metabolic dysregulation [1,5,8]. No studies have examined the mechanistic impact of increased fructose intake during pregnancy and subsequent adverse effects on offspring mitochondrial metabolism

Objectives

Methods

Results

Conclusion