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

• Published in: International journal of molecular sciences 2022-01, Vol.23 (2), p.999
• Main Authors: Smith, Erin Vanessa LaRae, Dyson, Rebecca Maree, Vanderboor, Christina M G, Sarr, Ousseynou, Anderson, Jane, Berry, Mary J, Regnault, Timothy R H, Peng, Lifeng, Gray, Clint
• Format: Article
• Language: English
• Subjects: Animals; Body composition; Catalytic activity; Chromatography, Liquid; developmental programming; Diet; Disease; Electron transport; Electron transport chain; Electron Transport Chain Complex Proteins - metabolism; Ethics; excess fructose intake; Fatty acids; Fatty Acids, Monounsaturated - blood; Female; Females; Fetal alcohol syndrome; Fetuses; Fructose; Fructose - adverse effects; Functional analysis; Glucose; Guinea Pigs; hepatic metabolism; Humans; Insulin resistance; Laboratory animals; Lipid metabolism; Lipid Metabolism - drug effects; Lipids; Lipogenesis; Liver; Male; Males; maternal fructose; Metabolic disorders; Metabolites; Mitochondria, Liver - drug effects; Mitochondria, Liver - metabolism; Mitochondrial DNA; mitochondrial function; mitochondrial metabolism; Nutrition research; Oxidation; Oxidative phosphorylation; Oxidative Phosphorylation - drug effects; Palmitoleic acid; Phosphorylation; Pregnancy; Prenatal exposure; Prenatal Exposure Delayed Effects - blood; Prenatal Exposure Delayed Effects - metabolism; Proteins; Proteomics; Proteomics - methods; Public health; Reactive oxygen species; Reactive Oxygen Species - metabolism; Sterol regulatory element-binding protein; Tandem Mass Spectrometry; Triglycerides; Triglycerides - metabolism; Water intake; Water intakes; Weaning; Western blotting; Young adults
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms23020999

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% / 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.