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Impact of maternal intermittent fasting on the development of metabolic disease in the offspring

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  • Full or part time
    Dr N Ashton
    Dr J Glazier
  • Application Deadline
    Applications accepted all year round
  • Self-Funded PhD Students Only
    Self-Funded PhD Students Only

Project Description

Pregnant Muslim women are exempt from the daily fast during the month of Ramadan; however many choose participate, wanting to share this experience with their families. Women who fast during the latter part of pregnancy have been reported to have smaller placentas. As fetal growth velocity and birth weight are positively correlated with placental dimensions, the narrower, lighter placenta in mothers who fasted during Ramadan was associated with having a smaller baby. Low birth weight is recognised as a risk factor for propensity to metabolic diseases in adulthood, including diabetes, cardiovascular disease and cancer.

We have developed a rat model of intermittent fasting during pregnancy, to mimic aspects of Ramadan fasting, which results in lighter placentas and smaller fetuses with reduced length, head and abdominal circumferences. Intermittent fasting affected glucose metabolism (a sensitive marker of metabolic perturbation and ‘stress’) in both the mother and fetus. Fasting mothers had lower blood glucose but similar insulin concentrations compared with controls; whereas the opposite was seen in the fetus.

The aim of the project is to determine the effect of maternal intermittent fasting during pregnancy on glucose metabolism in the offspring. The study will build on our initial observations to explore materno-fetal glucose transport and development of the endocrine pancreas and liver. Offspring will be followed into adulthood in order to assess their risk of developing metabolic syndrome (e.g. insulin resistance, dyslipidaemia, adiposity, high blood pressure). Key organs such as pancreas, liver, brain, kidney and adipose tissue will be examined; biomarkers of enhanced pro-inflammatory response, mitochondrial dysfunction and increased oxidative stress will be investigated. To identify potential underlying mechanisms, the methylome will be examined using genome-wide analysis to identify changes in epigenetic signatures.

This project interfaces with current ongoing studies investigating how maternal intermittent fasting during pregnancy influences offspring metabolism, physiology and function.


Training/techniques to be provided:

This project will employ a variety of in vivo and in vitro techniques to investigate the project objectives. The study will employ a rat model and will involve animal handling, breeding and the manipulation of both maternal and offspring diets, as well as assessment of physiological parameters e.g. glucose tolerance tests. Training in in vitro methodology will include molecular and biochemical techniques such PCR, immunoblotting, immunohistochemistry, enzyme activity and transporter assays.

The project will involve the use of laboratory rats; therefore applicants must be comfortable with the use of animals in biomedical research. Full training will be provided and the successful candidate will be expected to pass a Home Office personal licensee training course.

Funding Notes

Candidates are expected to hold (or be about to obtain) a minimum upper second class honours degree (or equivalent) in a relevant biological/medical science, molecular biology or related discipline. A Masters qualification in a similar area and/or previous research experience would be advantageous. Candidates with experience of in vivo studies are encouraged to apply.

This project has a Band 3 fee. Details of our different fee bands can be found on our website (https://www.bmh.manchester.ac.uk/study/research/fees/). For information on how to apply for this project, please our website (https://www.bmh.manchester.ac.uk/study/research/apply/).

Informal enquiries may be made directly to the primary supervisor.

References

Sibley, C., Glazier, J. & D'Souza, S.D. (1997). Placental transporter activity and expression in relation to fetal growth.
Experimental Physiology 82: 389-402.

Sibley, C.P., Brownbill, P., Dilworth, M. & Glazier, J.D. (2010). Adaptation in placental nutrient supply to meet fetal growth demand: Implications for programming. Placenta 31 (Suppl A), Trophoblast Research 24: S70-S74



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