Alteration in metabolic programming of first-generation offspring of diet-induced obese mothers.

Summary

Children exposed to diabetes in utero are prone to obesity and associated comorbidities, possibly due to detrimental exposure to diabetic intrauterine environment^1-4. The mechanisms by which in utero exposure to diabetes/obesity results in long-term consequences on offspring are poorly understood. Altered intrauterine metabolism and subsequent hormonal changes in offspring exposed to diabetes may contribute towards later obesity development⁵. Gut peptidesplay an important role in the regulation of body weight and glucose homeostasis. Glucagon-like peptide-1 (GLP-1), glucose‐dependent insulinotropic polypepide (GIP) and peptide-tyrosine-tyrosine (PYY) are key hormones secreted from intestinal and pancreatic endocrine cells and play critical role in regulating appetite, islet function and adiposity. This project aims to understand the impact of maternal obesity and hyperglycaemia on gut-pancreatic axis in offspring. Previous publications from our laboratory indicate adaptations of islet-derived GLP-1 and GIP during pregnancy⁶. More recently, we observed receptors expression for the aforementioned peptides in female reproductive organs suggesting key role of incretin peptides in reproductive function. Additionally, children born to diabetic mothers had increased circulating PYY and suppressed postprandial GLP-1 response⁵. High-fat (HF) feeding during pregnancy is also suggested to effect GIP-regulated metabolic pathways in male offspring⁷.

Objectives of the research:

The main objective of this project is to understand effects of on maternal dietary influence on offspring’s gut-pancreatic development. This study may unravel consequences of exposure to HF-diet in utero on islet and intestinal adaptations and determine subtle abnormalities in the activity of gut hormones that may contribute to metabolic disorders among children exposed to diabetes/obesity in utero.

Methods to be used:

To assess changes in islet/ intestinal morphometry and expression of GLP-1, GIP and PYY in endocrine cell population in first-generation offspring of normal chow and HF-fed female Wistar rats.

4-weeks-old female Wistar fed either chow or HF-diet (45%fat) for 14-weeks. Post 14-weeks feeding, females mated with control males. Postpartum, litter size, body weight and blood glucose of offspring will be monitored. Offspring will be sacrificed on day-21 and blood plasma, pancreata and small intestines will be collected. Islet and intestinal morphology (islet area, villus length/height, mucosal thickness), endocrine cell (GLP-1,GIP,PYY) population and colocalization will be assessed using immunohistochemistry. Hormone content will be measured using commercially available ELISA kits. This study will evaluate the effect of maternal fuel intake on gut-pancreatic hormonal adaptions in offspring.

Skills required of applicant:

Proficiency in designing, conducting, and analyzing research.

Ability to critically evaluate existing literature, identify gaps, and formulate research questions.

Understanding basic idea of obesity and diabetes with immunohistochemistry, handling tissues and proficiency in data analysis tools. Strong writing skills to produce clear, coherent, and well-structured research papers, thesis, and reports.

Effective time management, organization, and planning skills to manage the different phases of the research project. Ability to present research findings clearly and effectively, both in

Understanding of ethical considerations and integrity in conducting and presenting research.

Essential criteria

Applicants should hold, or expect to obtain, a First or Upper Second Class Honours Degree in a subject relevant to the proposed area of study.

We may also consider applications from those who hold equivalent qualifications, for example, a Lower Second Class Honours Degree plus a Master’s Degree with Distinction.

In exceptional circumstances, the University may consider a portfolio of evidence from applicants who have appropriate professional experience which is equivalent to the learning outcomes of an Honours degree in lieu of academic qualifications.

• Experience using research methods or other approaches relevant to the subject domain
• A comprehensive and articulate personal statement
• A demonstrable interest in the research area associated with the studentship

Desirable Criteria

If the University receives a large number of applicants for the project, the following desirable criteria may be applied to shortlist applicants for interview.

• First Class Honours (1st) Degree
• A comprehensive and articulate personal statement
• Use of personal initiative as evidenced by record of work above that normally expected at career stage.
• Applicants will be shortlisted if they have an average of 75% or greater in a first (honours) degree (or a GPA of 8.75/10). For applicants with a first degree average in the range of 70% to 74% (GPA 3.3): If they are undertaking an Masters, then the average of their first degree marks and their Masters marks will be used for shortlisting.
• Relevant professional qualification and/or a Degree in a Health or Health related area

Equal Opportunities

The University is an equal opportunities employer and welcomes applicants from all sections of the community, particularly from those with disabilities.

Appointment will be made on merit.

Funding and eligibility