Wednesday, 17 October 2012

Identically Different (Extra)

In Identically Different Tim Spector (Professor of Genetic Epidemiology at King's College London) looks at the 'heritability' of various diseases, illnesses and other physiologic phenomena.  He covers similar ground to Nesse in The Epigenetics Revolution but in a less technical style.

As with all these books, what is of particular interest to me is epigenetics can uncover with regard to obesity, and in this regard, Spector comes down firmly (but not exclusively) on the side of food reward,

  • "...we believed that different metabolic rates and different types of fat were the genetic factors in why people differed.  We now know that the brain may be more important.  The first and strongest gene found so far is called FTO, and is expressed in the brain, especially in the key reward centre of the pypothalamus in the base of the brain (hypothalamus means under-chamber in Greek).  For some rare humans who have two copies of the variant, chances of being obese increase by up to 70 per cent.  Experiments in rats and observations in humans have shown that having different variants of FTO genes directly alter the chosen diet - influencing total calories and fat content of food eaten and man release oxytocin - the cuddle hormone.  Other forms of a newly discovered gene called amylase we helped uncover dramatically alter the wish for starch and fatty foods and influence obesity.

      Most of the other 30 or more genes associated with obesity found to date are actually expressed mainly in the brain, not the fat or intestines or liver, where metabolism mainly occurs."

Obviously obesity has to be concerned with hormonal wash, and here we see mention of our old friend Ghrelin,
  • "We know there is a gene that codes of the Ghrelin protein, and so the threshold and intensity for the hunger signal has a general genetic influence.  While normal twins would be expected to have similar Ghrelin levels, a study of identical twins has shown that the hormone levels differ significantly between fat and thin discordant pairs, suggesting that once an individual has gained fat, this new environment and possibly diet alters the expression of Ghrelin."
 Interestingly, bariatric surgery (a gut bypass) is also believed to (favourably) change hormonal factors leading to weight loss, and also the importance of gut ecology,
  • "Within 48 hours of the operation to effectively bypass most of the stomach, sugar ind insulin levels of patients return to normal and stay that way for ten years in over 70 per cent of cases.  The conventional explanation is that this is due to malabsorption and that nutrients just pass through the gut quicker, but there is no hard evidence for this and many patients actually have constipation, suggesting that passage of food through the gut is if anything slower.  Some of these rapid changes could could be due changes in the gut hormones that signal the brain when it's hungry and full...However patients' eating habits don't alter dramatically, although they have more frequent small meals and less fatty foods.  What is also happening is that the gut bacteria change rapidly and suddenly take over new areas and alter metabolism."
Spector uncovers some exciting research on the methylation of gut bacteria in the intestine which turn-off bacterial genes that can 'kick-start the cancer process by disrupting the DNA in the cells of the stomach wall'!  A powerful concept for anyone who has taken a course of antibiotics - although anyone who eats highly processed modern foods may also do well to consider what kind of gut bacteria this may encourage to flourish.  Spector reports that our gut flora are drawn from a pool of 3 million unique bacterial genes, the profile of which can be hard to alter in places (our 'metagenome'),
  • "These genes make proteins that have a key role in many processes from breaking down carbohydrates and sugars to creating fats and vitamins.  Thus we possess a huge accessory genome that can influence how we filter and metabolise our diet and derive energy from it - as well as many other processes that we can only guess at."
So your lifestyle can influence the genetic expression in both your self and your offspring.  What you eat can affect your metagenome (gut flora/ecology).  But there is another thing to consider here - research from the Beijing Genomics Institute in China conducted an experiment that suggests bacteria can prefer the genes of some humans to others!  Did someone say feedback mechanism?  Could it be that fat loss is so difficult becuase you need to change your gut ecology?  An ecology that defends itself?

  • "These twin results show that bacteria can recognise and prefer the genes of certain humans to others.  Some of these bacterial species prefer younger or older hosts, and as there are major differences in gut flora between young and old people, some of these bacteria may turn out to be important in the ageing process itself.  Deep sequencing of 22 gut microbiomes from individuals in four countries has shown that our gut contents belong to three main distinctive groups, called 'enterotypes' - a bit like blood groups.  Strangely, these are not related to race or place of birth, and the groups may well behave very differently in affecting how we interact with our environment, diet, and even ageing.  Each of these has some dominant bacterial species.  Some bacterial species also prefer to live in hosts that produce different amounts of body fat."
This is truly incredible stuff!  I thoroughly recommend this book!

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