Wednesday, 26 September 2012

Fat, Fate & Disease

In Fat, Fate and Disease by Peter Gluckman and Mark Hanson, we see an attempt to synthesise the scientific research from various sources in to one volume that explains why our current strategy is not working, drawing heavily from evolutionary biology and evolutionary theory.  As you'd expect, epigenetics are a big part of the puzzle.

They pull some interesting examples of epigenetic 'predictive, adaptive response' from various sources of the animal world.  The Pennsylvanian meadow vole for example, can be born in either spring or autumn, which determines the thickness of it coat of fur.  The type and density of its hair follicles are set before birth, but temperature clues are thin on the ground as the temperature in the womb is pretty consistent.  The trigger in this case are melatonin levels in the mother which reflect the length of day and so the season.  They also indicate how biological decisions early in development can be outside of our individual control.  Butterflies also pull a similar trick.  Their wing colour needs to reflect the seasonal colour of foliage.  In this case the temperature the larva is exposed to triggers the relevant epigenetic change.

A final example is with genetically identical queen bees and worker bees. The worker bees develop mouth parts adapted to collect pollen with a metabolism suited to frequent short flights and shrunken reproductive organs. The queen bee develops a mouth suited to fighting, a metabolism suited to a single long flight and with ovaries prepared to lay thousands of eggs,
  • "The developmental path that the larva will take depends solely on what it eats in the first few days after hatching - fed on protein-rich royal jelly for only a few days and then with sugary nectar, the larva becomes a worker bee, while prolonged feeding on the royal jelly alone turns the larva in to a queen."
Their fate is NOT sealed thus.  If the queen dies, previously sterile workers may become reproductively active.  Their environment has changed their fate - although they never become 'complete' queens.

If you cast your mind back to my earlier post about the Dutch Hunger Winter you can see why researchers are taking seriously the notion of how nutrition might influence epigenetic change in humans.  Gluckman and Hanson go on to discuss malnutrition in Jamaica,
  • "Jamaica still has a high incidence of severe infant malnutrition, and children are admitted to [the Tropical Metabolism Research Unit in Kingston] in a terrible nutritional state every week.  Many families live on the edge of poverty and only one thing needs to happen - the father loses his job or leaves the home, the mother has another child, a hurricane strikes or just that the child gets an infection - and the child's nutritional state collapses.  Severely malnourished children may develop one of two syndromes: marasmus or kwashiorkor.  Infants with marasmus look terribly emaciated, with their muscles wasted away.  Infants with kwashiokor have swollen bodies with pot bellies distended by fluid accumulation...Infants with kwashiokor are more likely to die.  But tragically, even though they die of malnutrition, they still have fuel stores left in the muscle and fat in their bodies.  It is as if they cannot mobilise their fuel supplies, unlike marasmic children who seem to cling on to life, getting thinner and thinner, until there is no more fuel left to burn."
The big question is why do some children develop marasmus and some kwashiorkor given that the children were from similar backgrounds and exposed to similar levels of malnutrition?  The answer seemed to lay with birthweight,
  • "...marasmic children had lower birth weights than those who developed kwashiorkor.  It seemed that foetuses who were less well nourished before birth, and therefore grew less and had a lower birth weight, had predicted a poor nutritional environment and had adjusted their physiology to be good at mobilising their fuel supplies to withstand famine.  In contrast, foetuses who were better nourished and had higher birth weights had not predicted such famine.  When it struck they were not so well prepared..."
Gluckman and Hanson wanted to test this idea in a more controlled environment and recruited David Raubenheimer and Steve Simpson to look at 'appetite control and development history',
  • "In Jamaica, Rebenheimer and Forrester carefully measured appetite control in a group of survivors of famine , who had suffered either kwashiorkor or marasmus as young children.  These people are now between 25 and 40 years of age.  Sure enough, those people who had predicted a bad environment based on their prenatal cues had very different appetite control mechanisms from those of higher birth size..."
Gary Taubes made some interesting observations in GCBC about the presence of obesity in poor countries.  Looks like we might have one possible mechanism.

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