Fatso and the gene genie

By Tracy Purbrick
Primary Care Dietitian

I should be fat! Descended, as I am, from somewhat corpulent stock and having spent my most genetically malleable months attached, not to a breast, but a bottle. Sure I’ve resisted my biologically bequeathed destiny for nigh on 39 years, but if the papers are right, I’ll be upsizing sometime soon.

The reason I am doomed is the discovery of yet another fat gene and thus yet another reason to surrender to my fat fate. Actually, whilst this gene, the fatso (FTSO) gene, has been heralded by many as an obesity gene first, even the briefest of Googles trawls up a myriad more. There’s the PPARgamma2protein, MC4-R, Sarb1b and so the alphanumerical list rambles on. But whilst you might quibble over its primacy in the fat gene race, with a name like fatso it’s certainly the most media savvy.

So just how certain is this latest gene at portending whom will be portly? Apparently possessing one of the fatso genes increases the risk of obesity by 30 percent, whilst inheriting two increases it by nearly 70 percent; still not a fat guarantee. Strangely, whilst half the population has one such mutant copy, the remainder of the population is skewed heavily towards having none. And even for the least fortunate 16 percent who do face the double whammy, the actual average weight burden incurred, is a rather unspectacular three kilograms. Even the study’s author concedes that worldwide waist inflation is due to diet, not genes. But, the fact that the gene pool hasn’t changed in the past 20-30 years and neither presumably has that of our increasingly hefty pets, is a minor botheration in the way of a good story.

So why do we need to cling to a gremlin in our internal workings to explain away our weight, when the first law of thermodynamics already does such a sterling job? Well, it’s because we all know someone who eats twice as much as us, with half of the wobble to show for it. Or so we like to believe. Yet the notion of the ‘thrifty gene’ has of late been somewhat debunked. If people who are obese do have a genetic nudge that way, it’s not via any pathetically sluggish metabolism. When notoriously podge prone nations are studied, they have been found to tell as many porkies about their diets as the rest of us. What transpires is not so much a thrifty gene, but if anything, (as posited by Andrew Prentice, a perennial pursuer of obesity truth), a greedy one!

That is, they eat more in response to environmental cues. This possibility has been further investigated in a recent study with kids. Faced with a barrage of TV junk food ads, virtually all of the little blighters doubled their usual snacking. But those kids whose bones were already ‘well padded’, scoffed most rapturously of them all. However, that doesn’t prove genetically induced gluttony, any more than it absolves them of a weaker will. What it does suggest though is that rather than fiddling around in the human genome, a little tweaking of the environment could work wonders faster.

Let’s face it, any obesity gene of significant prevalence is likely to be recessive, polygenic and of low penetrance, thus not particularly influential, difficult to pin down and easily overpowered by will power. Even assuming genes could explain away a penchant for KFC or a phobia for physical exertion, where would any genetic discovery take the majority of us, beyond motivational collapse? If we could summon up an obesity ‘gene genie’ by rubbing some kitchen crockery, how would we wish to tweak our genetics and what would be the wisdom of it?

The number one foodie’s fantasy has to be a turbo charged metabolism, enabling them to eat more (preferably of the chocolate, chips and cakes variety), whilst staying slim. However, by revving up the metabolism, you also rev up free radical production. Indeed the only diet so far proven to promote longevity is a hypo-caloric - but nutritionally dense one. And, of course, turning up the calorie burners, in the long run, probably wouldn’t even result in staying slim. Inevitably, people would just up the ante on what they ate, staying plump, whilst indulging ever more. So whilst their own plodding footprint might look the same, their carbon one would inevitably expand, in line with their shopping baskets and till receipts.

So how about tinkering with the works, so that people simply couldn’t lay down any fat? Well, that genetic glitch already exists in the form of Berardinelli-Seip Syndrome. The victims of this condition possess virtually no body fat. Sound enticing? Well, with no where to store fat on their bodies, it just swills around their milky bloodstream, giving them high triglycerides, insulin resistance and a 100 fold increase in cardiovascular disease. Oh, and they also have to inject themselves daily with leptin, one of the satiety hormones normally made in the fat cells, to stave off the constant gnawing hunger.

But, of course! Leptin, the anti-hunger hormone… that has to be the answer! Indeed, after the millions of pharmaceutical industry dollars already invested, there’s a financial imperative to make darned sure it is. But after the initial excitement over leptin discovery, it has stunningly failed to live up to its promise. Leptin deficiency is, disappointingly, exceedingly rare. So in a bid to get a return on their cash, researchers instead turned to a possible leptin receptor deficiency. Yet again, though, this affliction is hardly rife, affecting only eight people out of 300 in a group already pre-selected for severe early onset obesity. And out of those afflicted few, six were from consanguineous families. Cue the next possible use; slipping it into baby milk on the rationale that breast milk contains leptin, but bottle milk doesn’t and bottle-fed babies are more likely to become obese. Well, that ‘bottle to blob’ link has also been recently scuppered. More worryingly though, a link between leptin and obesity related cancer is suspected, with leptin found to trigger colon cancer growth.

All this study into subduing hunger ignores one inconvenient truth. Very few people actually overeat to the state of obesity because of hunger. How many patients do we see, who, like the unfortunates with Prader Willi, would be prepared to shovel down frozen chips or rummage around in the garbage for soggy leftovers?

If you’re waiting for a gene genie to save you from the urge to splurge, you’ll have to wait more than one thousand and one nights. So, if you excuse me, I’d better lace up my trainers. I’ve got a big fat legacy to run away from.