You’ve heard it everywhere: your friends, your doctor, the New York Times, your personal trainer, virtually anyone who talks to you about health for more than five minutes will give you the same litany:  we need to lose weight to be healthy and all we need to do to achieve that loss is to change what we eat (fewer refined high glycemic index carbs, leaner meats, more fish, better quality fats, etc.) and, ultimately, how much of it we eat — otherwise we will not only get fat and look bad but also become insulin resistant, develop type 2 diabetes and have high cholesterol. Scary, right? But the fly in this particular ointment is that, notoriously, diets don’t work as designed.

Some people find intolerable the concept that genetics may determine our weight, our shape, our cholesterol and weight distribution.  For one thing some fear it “let’s people off the hook” and “gives them permission to eat whatever they want”.  Further, it fails to recognize the “moral superiority” of those who are able to remain thin.  I myself find this rather odd; wouldn’t it be better to worry less about what we eat and enjoy it more?  Anxiety reduction alone might help blood pressure and tempers.  Eating together in a spirit of joy rather than guilt or competition would — in my opinion — be a boon.

So along comes an article by Sandra Schreyer, David Cummings, G. Stanley McKnight and (ironically named) Renee LeBoef,  scientists from the University of Washington’s divisions of metabolism and pharmacology with their article: Mutation of the RIIβ Subunit of Protein Kinase A Prevents Diet-induced Insulin Resistance and Dyslipidemia in Mice  in Diabetes Vol 50 November 2001.

Now, 2001 is a long time ago (although, famously, Gregor Mendel’s work sat unnoticed for many, many years) and there has been much ground-breaking genetics work done since then, but to my knowledge, it all points in the same general direction: the cards we are dealt genetically determine in large part how we respond to our environment.  In this case, to food.

The cliff notes to this lengthy, erudite and somewhat hard-to-read (even for a doctor) work are these:  PKA (protein kinase A) signaling mediates much of the diabetes developed in response to obesity.  The above referenced RIIβ is a subunit of PKA which is expressed in brain and fat cells.  “Knockout mice”, those mice who genetically lack this subunit or the ability to make it (“express” it), are natively lean and are remarkably resistant to diet-induced obesity, even when fed a high calorie, high fat diet. (We all know these annoying “mice” among us who can eat everything and stay thin!).  In the experiment reported on at great length, knockout mice and normal (‘wild type’) mice were fed a high fat, high calorie diet and examined for weight gain, insulin levels, insulin sensitivity and glucose disposal (diabetes).  The mice who were lacking these aforementioned RIIβ subunits were leaner, had improved glucose disposal, insulin sensitivity and reduced insulin levels.  For you cardiologists out there, they also had reduced levels of VLDL and LDL cholesterols (the so-called “bad fats”).  Given their findings, the authors suggest that “targeting RIIβ would be an excellent therapy to reduce both obesity and metabolic disorders associated with obesity”.

Now I don’t know anything about what would be involved in “targeting RIIβ”, but my take away here was the refreshing discussion of a genetic susceptibility to obesity rather than thinly disguised rants about how “weak-willed” and “gluttonous” fat people are.  Why don’t they just eat less?  Well, because not only is that unpleasant but it also doesn’t work.

Now, can we get on with finding something that does?