My latest review paper now available online

Nutrition in early life and the programming of adult disease: a review

Abstract

Foetal development and infancy are life stages that are characterised by rapid growth, development and maturation of organs and systems. Variation in the quality or quantity of nutrients consumed by mothers during pregnancy, or infants during the first year of life, can exert permanent and powerful effects upon developing tissues. These effects are termed ‘programming’ and represent an important risk factor for noncommunicable diseases of adulthood, including the metabolic syndrome and coronary heart disease. This narrative review provides an overview of the evidence-base showing that indicators of nutritional deficit in pregnancy are associated with a greater risk of type-2 diabetes and cardiovascular mortality. There is also a limited evidence-base that suggests some relationship between breastfeeding and the timing and type of foods used in weaning, and disease in later life. Many of the associations reported between indicators of early growth and adult disease appear to interact with specific genotypes. This supports the idea that programming is one of several cumulative influences upon health and disease acting across the lifespan. Experimental studies have provided important clues to the mechanisms that link nutritional challenges in early life to disease in adulthood. It is suggested that nutritional programming is a product of the altered expression of genes that regulate the cell cycle, resulting in effective remodelling of tissue structure and functionality. The observation that traits programmed by nutritional exposures in foetal life can be transmitted to further generations adds weight the argument that heritable epigenetic modifications play a critical role in nutritional programming.

 

Venturing into the lab

Hold on to your hats… I am going into the lab today. To work. To do bench science. I am scared and no doubt the other people in the lab will be equally disturbed. Generally going into the lab is about me looking for somebody I need to talk to, or checking freezer temperatures. This is the real thing though and I will have to work out how to operate a Gilson again. 

I just checked my lab book and my last day in the lab (a disaster judging from the notes) was on April 5th 2011.

Progress with the book

Editing my book as proved extremely challenging. I thought that it would be very easy to take the previously published text and make some tweaks and updates, move some bits around, add in extra details, remove some bits and bobs, etc. It turns out it’s not like that at all. To do it that way would be a waste of time and short-changes the punters who will go on to buy the new edition. Yes, there is tweaking and adjusting to do, but there is also a huge wadge of more extensive stuff to do. So far I have worked on one chapter, just a nice easy one, and surprisingly I have found myself deleting big sections to make myself properly rewrite them from scratch. That makes for a lot more work, but a fresher feel to the end product.

 

Of course having started on that process, the publisher informs me that they will provide me with Word copies of the original post-production and that I should be working from those instead of my own original files. That makes a lot of sense. It does make for something of a hiatus, but to fill the space I have embarked on the task of refreshing all of the figures. The publisher wants there to be a lot more in the new edition and to be honest I wasn’t happy with the quality of a some of the originals. I am in the process of updating everything and creating new figures, which will then go off to Wiley for their professional illustrators to work with. That’s exciting and allows me to be more imaginative about what I create- they can work from loose sketches to produce things that are way beyond my ability.

And the all important soundtrack for the second edition… Well, it seems to have evolved into a collection of three albums by Glass Hammer. Not everyone’s cup of tea and they have taken a long time to grow on me. They’re very long albums and the suite of three will last me a whole morning and keep me in the writing zone.

Some travel is planned

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No sabbatical would be complete without some elements of travel, I gather. Whenever I mention that I am on sabbatical, people ask me, “Where are you going?” and I lamely reply, “Oh, I’m just staying here”. Just staying here, is of course extremely productive and already great things have been happening and I am producing ideas and writings and working impressively ahead of the schedule that I have imposed upon myself.
But, some travel is going to happen after all it seems. I have just returned from a trip to Milan to see my collaborators there. The data is coming together nicely and I think we should have an exciting publication before too long. We had some good discussions and I think that there will be some strong grant applications arising from the collaboration (reviewers willing). The next trip that I have just booked is to a Keystone Symposium meeting (Epigenetic Programming and Inheritance) in Boston. Hopefully we will be presenting an abstract on the Milan work there. It’s already had an outing at the Wellcome Hinxton meeting last year, but this would be a very different crowd and it ail be of interest to see how the work plays with them. Then, there will be a trip to California where I will be Visiting Scientist in the Center for Perinatal Biology of Loma Linda for a few days.  A bit of a US tour is shaping up…

A piece of MAGIC

The Langley-Evans Blog hasn’t previously had a guest blogger, but I am always open to new ideas. Here’s a piece from PhD student Sarah Ellis.

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I’m a dietitian not a magician but I am involved with MAGIC.

What I mean with this statement is that, as a clinical dietitian, I have to manage people’s expectations about what can be achieved with dietetic input alongside their commitment to make changes to improve their health. There is no magic wand moment…

Despite no magic wand I am involved with MAGIC, or less snappy but more explanatory, the Managing weight in pregnancy study. This is a collaborative study between the University of Nottingham and Nottingham University Hospitals QMC campus. The main aim of the study is to find ways to support mums in getting back to a healthy weight once they have had their baby.

The sad truth is that as a nation we are getting heavier. Entering pregnancy with excess weight, or gaining too much weight during pregnancy, can have some fairly awful outcomes for both mum and baby. It is also hard to lose this excess weight once baby arrives. Despite this, the UK has no specific guidelines for weight gain in pregnancy. The main interest of the MAGIC team is in what the main predictors are of excess weight gain or retention of weight after delivery. Our aim is to come up with new ways of helping women optimise their weight and health.

The best way to find out how to support someone in achieving a goal like this is to ask them what might help. Pregnant ladies visiting the Queens Medical Centre in Nottingham for either their 12 or 20 week scan were invited to take part in data collection over the next 18 months. All data collection is questionnaire based although mum’s were weighed and measured when they first agreed to take part. The questionnaires are sent out at specific times throughout the pregnancy and during the year after the birth. They ask a wide variety of questions around issues that may affect weight and cover diet, physical activity, social support etc. All of this is then painstakingly added to a data sheet. We’re now sitting on a pile of data from the questionnaires we received from the mums-to-be, and are beginning to get back the post pregnancy questionnaires.

And here’s a call to arms – We Need You (student dietitians)!

Here’s an amazing opportunity to be involved in this study and use some of this data for your dissertation. There’s a mix of quantitative and qualitative data so something for everyone. Plus you get to work with a top-notch team of researchers (did I mention my involvement). More information about the study can be found here: http://clinicaltrials.gov/show/NCT01770522
If you’re interested speak with me at sbxse@nottingham.ac.uk
I look forward to welcoming you to the MAGIC team.

What do you think of it so far?

What do you think of it so far?

Well I couldn’t resist a bit of Eric Morecambe. I watched a great collection of M&W sketches the other night, which made me laugh out loud, so why not borrow the great man’s catch phrase.

Two days back at work after the Christmas break and colleagues in adjoining offices have commented on my smiley face already. I am on sabbatical and so far I like it. This period of study leave means that I don’t have any teaching responsibilities and my administrative duties are slightly reduced (I will pick and choose what I want to do to some degree) and I am therefore free to focus on research. Two days isn’t much to go on and with the students away still the true effects of the sabbatical are yet to manifest, but even so, I feel different. Maybe all the sleeping I did in the holidays explains it, but maybe the psychological benefits of having reduced pressures on my time are coming through. I am enjoying myself with some writing to begin with. Chapter 2 of my book is undergoing it’s refresh ready for the second edition and I have spent some time generating some new diagrams, reading around some of the sections that had become a bit tired and inserting new information. There is a new paper bubbling away on the edges of consciousness too, so maybe that is the next project.

Meanwhile, Genes and Nutrition have published our paper on cafeteria feeding and the expression of the insulin signalling pathway. The pdf of the article can be downloaded here. I am very impressed by their speed in handling this and will revisit them with future work.

An immensely important paper

The paper which came out of the MRC funded collaboration with Adrian Clark, Elia Stupka and others has finally been published in PlosOne after a fairly difficult gestation. 

Genome-Wide Methylation and Gene Expression Changes in Newborn Rats following Maternal Protein Restriction and Reversal by Folic Acid

This paper describes the findings of genome wide assessment of DNA methylation assessed by MBD sequencing and whole genome microarray in a set of livers obtained from neonatal rats exposed to either control or low protein diets (with or without folate supplementation). We found differential expression of 618 genes at 5% FDR and 131 at 1% FDR associated with protein restriction. As with other microarray studies that we have performed, the main pathways affected were association with cell cycle regulation and DNA maintenance. Incredibly the folate supplementation removed all of these gene expression changes- a finding consistent with earlier work and strongly supporting the hypothesis that DNA methylation and availability of methyl donors plays a major role in programming. Protein restriction was associated with widespread differential methylation (1183 DMRs). Again, this effect was highly sensitive to folate availability. Surprisingly there was virtually no overlap between the DMR and gene expression differences, a finding that was difficult to explain. 

 

In my view this is one of the most important papers that I have published. It offers some useful insight into the role of epigenetics in fetal programming. It confirms that the cell cycle plays a key role in the programming of tissue development and long-term health and that availability of folate is a modulator of the effects of protein undernutrition, emphasising that folate sufficiency in pregnancy is of critical importance for lifelong health.