Another paper accepted from our British Heart Foundation funded project

I’m very happy to report that Scientific Reports has accepted our paper entitled, ‘The impact of exposure to cafeteria diet during pregnancy or lactation on offspring growth and adiposity before weaning.’ This is work from the BHF funded project of Grace George who secured her PhD earlier this year.

 

The impact of exposure to cafeteria diet during pregnancy or lactation on offspring growth and adiposity before weaning.

Grace George, Sally A.V. Draycott, Ronan Muir, Bethan Clifford, Matthew J. Elmes, Simon C. Langley-Evans

Exposure to maternal obesity during early-life can have adverse consequences for offspring growth and adiposity. We aimed to assess the relative contributions of exposure to maternal obesity, induced by a highly varied cafeteria diet, during pregnancy and lactation on these measures in rat offspring prior to weaning. Female Wistar rats were fed either a control (C) or cafeteria diet (O) for 8 weeks before mating, throughout pregnancy and lactation. Offspring were cross-fostered at birth to a dam on the same (CC,OO) or alternate diet prior to birth (CO,OC). Feeding a cafeteria diet based on 40 different foods, was associated with a sustained period of elevated energy intake before birth and during lactation (up to 1.7-fold), through increased sugar, total fat and saturated fat intake, and lower protein consumption. Cafeteria fed dams sustained greater weight than animals fed a control chow diet and greater perirenal adiposity by the end of lactation. Exposure to obesity during pregnancy was associated with lower offspring birth weight and body weight in early-postnatal life. In contrast, exposure during lactation alone reduced offspring weight but increased adiposity in male CO offspring before weaning. This research highlights that exposure to maternal obesity during lactation alone can programme adiposity in a sex specific manner.

 

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New paper accepted

I’m very pleased to report that we have had a paper accepted for publication in the Journal of the Developmental Origins of Health and Disease. The work entitled ‘Expression of cholesterol packaging and transport genes in human and rat placenta: impact of obesity and a high-fat diet’, details some interesting observations of commonality between rodent and human placentas in response to over-nutrition. The work is a collaboration between our group at Sutton Bonington, Raheela Khan at Derby Medical School and Bev Muhlhausler in Adelaide.

Expression of cholesterol packaging and transport genes in human and rat placenta: impact of obesity and a high-fat diet

Sally Draycott, Zoe Daniel, Raheela Khan, Beverly Muhlhausler, Matthew Elmes, Simon Langley-Evans

Increasing evidence suggests that sub-optimal maternal nutrition can have implications for the developing offspring. We have previously shown that exposure to a low protein diet during gestation was associated with upregulation of key genes associated with cholesterol packaging and transport within the placenta. This study aimed to elucidate the effect of altering maternal dietary linoleic acid (LA; omega-6): alpha-linolenic acid (ALA; omega-6) ratios as well as total fat content on placental expression of genes associated with cholesterol transport. A potential link between maternal BMI and association with increased expression of these key genes in human placental samples was also evaluated. Placentas were collected from 24 Wistar rats at 20 d gestation (term=21-22d gestation) that had been fed a diet containing varying fatty acid compositions during pregnancy, and from 62women at the time of delivery. Expression of 14 placental genes associated with cholesterol packaging and transfer were assessed in rodent and human samples by qRT-PCR. In rats, placental mRNA expression of ApoA2,ApoC2, Cubn, Fgg, Mttp and Ttrwas significantly elevated (3-30 fold) in animals fed on high linoleic acid (LA) diets with a higher fat content (36% fat vs 18% fat), suggesting increased cholesterol transport across the placenta in this group. In women, maternal BMI was associated with fewer and less consistent alterations in gene expression. In summary, sub-optimal maternal nutrition is associated with alterations in the expression of key genes associated with cholesterol transport and may contribute to altered fetal development and potentially programme disease risk in later life in a rat model. Further investigation of human placenta in response to specific dietary interventions is required. These results showed striking similarities to those observed in our previous work in rats exposed to a low-protein diet.

A new way of working

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One of the highlights of my week has been the acquisition of a new standing desk. This was previously used by a colleague who left the University at the end of June, and so I’ve abused my Head of School privilege to liberate it. I’ve suffered with back problems for many years (including a spectacular herniated disk in 2012, which I have never really recovered from) and so I’m going to see if standing for some of the day makes things better than slouching in a chair all day.

The import of a new desk has created a lot more room in my tiny office and so I’m feeling quite excited by all the space too.

My desk has an electric control that allows me to set it to any height, and so the plan is to spend about 3 hours a day with it raised up to about elbow level for standing work (as in picture), and the remainder of the day has it down in seated mode. I’m finding that I am automatically selecting different types of task for each position. Reading and intense writing gets done sitting down, whilst I answer emails and do editing jobs standing up.

Among the positives I noted so far are:

  1. I’ve actually had some standing up meetings with visitors to the office. That keeps them shorter and by standing by the screens we have focused on specific tasks.
  2. I’ve taken a lot more steps this week- I wander around when I’m thinking if I’m working in standing mode
  3. When I am standing I am less prone to procrastination or daydreaming- in standing mode I am very focused

So far the negatives that I have noticed are:

  1. I am a lot more tired at the end of the day
  2. My feet and knees are hurting- they aren’t used to working so hard
  3. I still haven’t worked out the best ‘mode’ for different tasks
  4. I like listening to music while I work and there is a tendency to either dance, or pretend that I am playing keyboards in a band, whilst I am working. Both are very embarrassing if someone comes into the office without me noticing. The new layout has me with my back to the door. Thufir Hawat’s admonition to Paul Atreides is ingrained in my brain, so I’m most uncomfortable.

New paper accepted

We recently had the very good news that former PhD student Grace George (now based in New Zealand) has had her first paper accepted for publication in Scientific Reports. Grace’s PhD considered the effect of feeding a cafeteria diet to rats pre-pregnancy, during pregnancy and during lactation, on the metabolic health of the resulting offspring.

Ironically, this first paper accepted is the second in a series. It looks at the post-weaning characteristics of the offspring. The first in the series describes the impact of the diet on maternal weight and nutrient intake, and is currently under review at the same journal.

 

Exposure to maternal obesity during suckling outweighs in utero exposure in programming for post-weaning adiposity and insulin resistance in rats.

Grace George, Sally A.V. Draycott, Ronan Muir, Bethan Clifford, Matthew J. Elmes, Simon C. Langley-Evans.

Abstract

Exposure to maternal obesity during early development programmes adverse metabolic health in rodent offspring. We assessed the relative contributions of obesity during pregnancy and suckling on metabolic health post-weaning.Wistar rat offspring exposed to control (C) or cafeteria diet (O) during pregnancy were cross-fostered to dams on the same (CC,OO) or alternate diet during suckling (CO,OC) and weaned onto standard chow. Measures of offspring metabolic health included growth, adipose tissue mass, and 12-week glucose and insulin concentrations during an ipGTT.Exposure to maternal obesity during lactation was a driver for reduced offspring weight post-weaning, higher fasting blood glucose concentrations and greater gonadal adiposity (in females). Males displayed insulin resistance, through slower glucose clearance despite normal circulating insulin and lower mRNA expression of PIK3R1, SREBP1-c and PIK3CB in gonadal fat and liver. In contrast, maternal obesity during pregnancy up-regulated the insulin signalling genes IRS2, PIK3CB and SREPBP1-c in skeletal muscle and perirenal fat, , favouring insulin sensitivity. In conclusion exposure to maternal obesity during lactation programmes offspring adiposity and insulin resistance that overrides exposure to an optimal nutritional environment in uterothat cannot be alleviated by a nutritionally balanced post-weaning diet.

Shaking off social media

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After many years I have almost completely weaned myself off personal social media. Facebook was shed around a year ago. I became deeply suspicious of their data harvesting activities following the Cambridge Analytica scandal and it was easily lost from my portfolio. Twitter clung on tenaciously despite several attempts to leave, and I am now a month free from it. The level of hatred, bile, and unpleasantness became too much to bear. Whilst the platform clearly has some benefits and is undoubtedly a good way to get a message out to a mass market, those benefits pale compared to the mental health impact.

Being free of the trivia of social media is saving me time, avoiding the stress of being exposed to right wing scumbags and racists and is a real plus for me. I think I am enjoying aspects of life more. I am going out and looking at the world without that stupid feeling that I need to tell complete strangers what I am doing and providing a photo to go with it. I’m glad I have moved on.

This blog is of course a form of social media and will still be circulated via LinkedIn. I feel more in control though. I will post occasionally and almost always on professional issues, plus the right for others to reply is limited and comments can be vetted.

The blog has become a bit moribund recently but it will have more content from now on. Not quite sure yet, but expect some insights on leadership, given that is now my role in academia.

Our latest paper on cafeteria diet, learning and behaviour in rodents.

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The prefrontal cortex (PFC) undergoes protracted postnatal development such that its structure and behavioural function may be profoundly altered by environmental factors. Here we investigate the effect of lactational dietary manipulations on novel object recognition (NOR) learning and PFC monoamine neurotransmitter metabolism in early adolescent rats. To this end, Wistar rat dams were fed a high caloric cafeteria diet (CD) during lactation and resultant 24–26 day old offspring exposed to NOR testing and simultaneous PFC dopamine and serotonin metabolism measurement. In the second NOR choice trial where one familiar and one novel object were presented controls explored the novel preferentially to the familiar object both after a 5 min (P < 0.001) or 30 min (P < 0.05) inter-trial intervals (ITI). By contrast, offspring from dams fed on lactational CD failed to show any significant preference for the novel object at either time point. Compared with chow fed controls, their average exploration ratio of the novel object was lower after the 5 min ITI (P < 0.05). Following a 60 min ITI, neither CD nor control offspring showed a preference for the novel object. PFC dopamine metabolism was significantly reduced in the CD group (P < 0.001), whereas serotonin metabolism was increased (P < 0.001). These results suggest that an obesogenic lactational diet can have a detrimental impact on cognition in adolescent offspring associated with aberrant PFC serotonin and dopamine metabolism.

 

Full text is available at:

Voigt P, Clifford B, Moreton E, Tiplady S, Baron P, Langley-Evans S, McCall S, Fone KCF (2019). Impact of early exposure to a cafeteria diet on prefrontal cortex monoamines and novel object recognition in adolescent rats.Behavioural Brain Research363, 191-198.

Second magnesium paper published

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The second paper from Lujain Almousa’s work on magnesium and human umbilical vein endothelial cells has been published in Magnesium Research. The full reference is:

Almousa LA, Salter AM, Langley-Evans SC, (2018). Varying magnesium concentration elicits changes in inflammatory response in human umbilical vein endothelial cells (HUVECs). Magnesium Research31, 99-109.

The abstract is below.

The aims of this study were to determine whether low concentrations of magnesium in vitroexacerbated the human umbilical vein endothelial cell (HUVEC) response to inflammatory challenge, and whether expression of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) through the toll-like receptor 4 (TLR4) played a role in this process. HUVECs were incubated with different concentrations of Mg (low- 0.1mM, control- 1mM, high- 5mM) for 72 h before being stimulated with bacterial lipopolysaccharide (LPS) for 4 h. The response of cells to LPS was greater in cells cultured in low Mg, relative to control cells and suppressed in high Mg. Expression of NF-κB was increased in low-Mg and decreased with high Mg. Low Mg increased the expression of TLR4 mRNA, but only in the presence of LPS. Antibody blockade of TLR4 but not TLR2 blunted the response of cells to LPS in low Mg, such that they were similar to unblocked 1mM Mg cells. Associations of Mg with cardiovascular disease may therefore relate to inflammatory responses mediated through the TLR4/NF-κB pathway.