Lipid traffic analysis reveals the impact of high paternal carbohydrate intake on offsprings' lipid metabolism

Furse, Samuel; Watkins, Adam; Hojat, Nima; Smith, James M.; Williams, Huw E. L.; Chiarugi, Davide; Koulman, Albert

doi:10.5281/zenodo.4309347

Cited by 4 publications

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“…The novel R code developed in the present study for Lipid Traffic Analysis v2.3 is in Supplementary file 2. LTA v1.0 is available publicly available through Zenodo (Furse et al, 2021a) and BioRxiv (Furse et al, 2020b). The abundance analysis for the present study is shown in Supplementary file 3.…”

Section: Supplementary Informationmentioning

confidence: 99%

Paternal Nutritional Programming of Lipid Metabolism is Propagated Through Sperm and Seminal Plasma

Furse¹,

Watkins

Williams

et al. 2021

SSRN Journal

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Section: Supplementary Informationmentioning

confidence: 99%

Paternal Nutritional Programming of Lipid Metabolism is Propagated Through Sperm and Seminal Plasma

Furse¹,

Watkins

Williams

et al. 2021

SSRN Journal

Self Cite

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Paternal nutritional programming of lipid metabolism is propagated through sperm and seminal plasma

et al. 2022

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Background The paternal diet affects lipid metabolism in offspring for at least two generations through nutritional programming. However, we do not know how this is propagated to the offspring. Objectives We tested the hypothesis that the changes in lipid metabolism that are driven by paternal diet are propagated through spermatozoa and not seminal plasma. Methods We applied an updated, purpose-built computational network analysis tool to characterise control of lipid metabolism systemically (Lipid Traffic Analysis v2.3) on a known mouse model of paternal nutritional programming. Results The analysis showed that the two possible routes for programming effects, the sperm (genes) and seminal plasma (influence on the uterine environment), both have a distinct effect on the offspring’s lipid metabolism. Further, the programming effects in offspring suggest that changes in lipid distribution are more important than alterations in lipid biosynthesis. Conclusions These results show how the uterine environment and genes both affect lipid metabolism in offspring, enhancing our understanding of the link between parental diet and metabolism in offspring.

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A mouse model of gestational diabetes shows dysregulated lipid metabolism post-weaning, after return to euglycaemia

et al. 2022

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Background Gestational diabetes is associated with increased risk of type 2 diabetes mellitus and cardiovascular disease for the mother in the decade after delivery. However, the molecular mechanisms that drive these effects are unknown. Recent studies in humans have shown that lipid metabolism is dysregulated before diagnosis of and during gestational diabetes and we have shown previously that lipid metabolism is also altered in obese female mice before, during and after pregnancy. These observations led us to the hypothesis that this persistent dysregulation reflects an altered control of lipid distribution throughout the organism. Methods We tested this in post-weaning (PW) dams using our established mouse model of obese GDM (high fat, high sugar, obesogenic diet) and an updated purpose-built computational tool for plotting the distribution of lipid variables throughout the maternal system (Lipid Traffic Analysis v2.3). Results This network analysis showed that unlike hyperglycaemia, lipid distribution and traffic do not return to normal after pregnancy in obese mouse dams. A greater range of phosphatidylcholines was found throughout the lean compared to obese post-weaning dams. A range of triglycerides that were found in the hearts of lean post-weaning dams were only found in the livers of obese post-weaning dams and the abundance of odd-chain FA-containing lipids differed locally in the two groups. We have therefore shown that the control of lipid distribution changed for several metabolic pathways, with evidence for changes to the regulation of phospholipid biosynthesis and FA distribution, in a number of tissues. Conclusions We conclude that the control of lipid metabolism is altered following an obese pregnancy. These results support the hypothesis that obese dams that developed GDM maintain dysregulated lipid metabolism after pregnancy even when glycaemia returned to normal, and that these alterations could contribute to the increased risk of later type 2 diabetes and cardiovascular disease.

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Lipid traffic analysis reveals the impact of high paternal carbohydrate intake on offsprings' lipid metabolism

Cited by 4 publications

References 0 publications

Paternal Nutritional Programming of Lipid Metabolism is Propagated Through Sperm and Seminal Plasma

Paternal Nutritional Programming of Lipid Metabolism is Propagated Through Sperm and Seminal Plasma

Paternal nutritional programming of lipid metabolism is propagated through sperm and seminal plasma

A mouse model of gestational diabetes shows dysregulated lipid metabolism post-weaning, after return to euglycaemia

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