Show simple item record

dc.contributor.advisorGray, Clint
dc.contributor.advisorDyson, Rebecca
dc.contributor.advisorBerry, Mary
dc.contributor.authorSmith, Erin Vanessa La Rae
dc.date.available2021-05-26T21:50:01Z
dc.date.copyright2021
dc.identifier.citationSmith, E. V. L. R. (2021). Excess maternal fructose intake and the developmental programming of mitochondrial function and lipid metabolism in adult offspring (Thesis, Doctor of Philosophy). University of Otago. Retrieved from http://hdl.handle.net/10523/11963en
dc.identifier.urihttp://hdl.handle.net/10523/11963
dc.description.abstractExcess dietary fructose is a major public health concern. Evidence shows increased fructose intake can cause insulin resistance, hepatic de novo lipogenesis, hypertriglyceridemia, obesity and non-alcoholic fatty liver disease (NAFLD). However, little is known about the effects of fructose during pregnancy and its influence on offspring development and predisposition to later-life disease. To determine whether moderately increased maternal fructose intake could have health future consequences on offspring, we have 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; 10% kcal from fructose) ad-libitum 60 days prior to mating and throughout gestation. Weanling Offspring were culled at weaning, day 21 (d21) and adolescent offspring at 4-months (4M). Compared to CD dams, FD dams had altered glucose metabolism and increased milk free fatty acid content. Matsuda-DeFronzo insulin sensitivity index (M-ISI) from OGTT plasma showed no significant difference in whole-body insulin sensitivity between FD and CD dams 60 days post-dietary intervention and during mid-gestation. Fetal exposure to increased maternal fructose resulted in offspring with significantly altered serum free fatty acids at day 0, 7, 14 and 21 (including pentadecanoic acid (15:0), dma16:0, margaric acid (17:0) palmitoleic acid, total omega-7 and total saturates), increased levels of uric acid and triglycerides were also observed at d21. In male and female fructose offspring, proteomic analysis revealed that key markers of mitochondria function, oxidative phosphorylation, NRF-2 pathways were significantly altered. Western blot analysis confirmed these findings by increased protein abundance in complex II & IV and key enzymes involved in hepatic de novo lipogenesis (FAS, SREBP-1C). In adult male and female fructose offspring (4 month) were observed to also have very similar changes in pathways involved in fatty acid B-oxidation, oxidative phosphorylation and mitochondrial function. Similar to d21 fructose offspring, adults also displayed programmed increases in key enzymes of de novo lipogenesis (FAS and SREBP-1c), mitochondrial function (Complex II & IV) and consistently increased palmitoleic acid at all time-points (day 0 to 4 month of age). We have demonstrated that excess maternal fructose intake during pregnancy and not lactation can cause significant changes in maternal metabolic function and milk composition, which programmes weanling and adult offspring hepatic mitochondrial function, de novo lipogenesis and metabolism. Taken together, these changes in pregnancy outcomes and feto-maternal condition may underlie their offspring’s predisposition to metabolic dysfunction during later-life.
dc.format.mimetypeapplication/pdf
dc.language.isoen
dc.publisherUniversity of Otago
dc.rightsAll items in OUR Archive are provided for private study and research purposes and are protected by copyright with all rights reserved unless otherwise indicated.
dc.subjectdevelopmental programming
dc.subjectmaternal fructose
dc.subjectmilk composition
dc.subjectpalmitoleic acid
dc.subjectfree fatty acids
dc.subjecthepatic lipids
dc.subjecthepatic function
dc.subjectomega-7
dc.subjecthepatic metabolic function
dc.subjecthepatic mitochondrial function
dc.subjectde novo lipogenesis
dc.subjectbeta-oxidation
dc.subjectoxidative phosphorylation
dc.subjectcomplex II
dc.subjectcomplex IV
dc.subjectSREBP-1c
dc.subjectFAS
dc.subjectVDAC1
dc.subjectfructose
dc.subjectmitochondria
dc.titleExcess maternal fructose intake and the developmental programming of mitochondrial function and lipid metabolism in adult offspring
dc.typeThesis
dc.date.updated2021-05-26T01:52:08Z
dc.language.rfc3066en
thesis.degree.disciplinePaediatrics and Child Health, UOW
thesis.degree.nameDoctor of Philosophy
thesis.degree.grantorUniversity of Otago
thesis.degree.levelDoctoral
otago.interloanno
otago.openaccessOpen
otago.evidence.presentYes
otago.abstractonly.term26w
 Find in your library

Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record