Fight Aging!

Research into treatments for the direct consequences of obesity may be, like much of aging research at the moment, the cover story set up by metabolic researchers in order to raise funds from a system that demands some connection, however tenuous, to the end goal of building treatments. In fact the principal goal of these scientific groups is to catalog and completely understand the massive complexity of cellular metabolism. Making use of that knowledge for any purpose other than to speed up other areas of the cataloging process is a distant second concern. A lot of modern medical research makes much more sense if viewed through this lens, though I can't vouch for the accuracy of its cynicism. It is generally true that knowledge is the primary goal of science, while it is more typically the engineering disciplines whose members work on building new applications of that knowledge. The line between scientist and engineer - between researcher and clinician - was always blurry and indistinct, however, and remains so today.

We live in a world in which wealth has been generated to such an extent that our natural urges, evolved for scarcity, now guide us to harm ourselves. Food, transport, and comfort are so cheap in wealthier regions of the world that simply failing to care and plan for diet and health will turn a thin individual into a considerably overweight individual in a matter of a handful of years. In some parts of Asia the transition from rural subsistence poverty to a society of such wealth happened in a single lifetime, bringing the demographics of disease and longevity into line with the US and Western Europe in that short span of years. Thus there are a lot of overweight individuals nowadays: we are a lot wealthier today even than fifty years ago in measures that matter, such as cost of calories and transportation. As a result a lot more money flows into medical services related to the health consequences of being overweight, and - follow the money - a large amount of funding exists for work on medical means to address these conditions. This is largely centered around work on treating type 2 diabetes, but it is also true that there is a greater level of funding for numerous other conditions much more commonly suffered by those who are overweight.

There is far less funding for the strategy of simple self control and just eating less, but that's what you get in an age of comfort. People want to be told they are fine, there is nothing they did wrong, and that the research community is working on zero-effort, write-a-check methods for making everything right in the world. People don't want to be told to adjust their expectations and diet while simultaneously exercising their willpower, even if that approach can reverse being overweight and reverse type 2 diabetes to boot. A lot of wishful thinking sloshes around in this ecosystem.

The inevitable consequence of giving a lot of researchers a lot of money to do something about obesity, even if they are principally focused on building the Grand Map of Metabolism, is that someone, somewhere, might actually come up with a treatment that works. I can assure you that there is a lot more funding out there for work on obesity and type 2 diabetes, conditions that the vast majority of patients choose to suffer - and worse, choose on a daily basis to continue to suffer - than for meaningful research into treating aging. Does success make it all worthwhile in comparison to other things those resources might have purchased in the research community? That is a question without an answer.

The best hypothetical treatment for obesity is probably one that does absolutely nothing other than make the patient eat less. That seems to be the case in the research noted below, so one has to wonder to what degree the rest of the panoply of effects they describe are relevant to the end result:

Another success on the path to cure adult-onset diabetes, obesity

A new treatment for adult-onset diabetes and obesity developed by researchers has essentially cured lab animals of obesity, diabetes and associated lipid abnormalities through improved glucose sensitivity, reduced appetite and enhanced calorie burning. In preclinical trials, the new peptide - a molecular integration of three gastrointestinal hormones - lowered blood sugar levels and reduced body fat beyond all existing drugs.

These preclinical results advance the clinical work the team announced last year that a peptide combining the properties of two endocrine hormones, GLP-1 and GIP, was an effective treatment for adult-onset diabetes. This new molecule includes a third hormone activity, glucagon. "A number of metabolic control centers are influenced simultaneously, namely in the pancreas, liver, fat depots and brain. The benefits of the previously reported individual co-agonists have been integrated to a single molecule of triple action that provides unprecedented efficacy to lower body weight and control metabolism."

The triple hormone specifically and equally targets three receptors of GLP-1, GIP and glucagon. GLP-1 and GIP predominantly contribute to enhancing insulin action and reducing blood glucose. GLP-1 also curbs appetite, while glucagon primarily increases the long-term rate at which calories are burned and improves liver function.

A rationally designed monomeric peptide triagonist corrects obesity and diabetes in rodents

We report the discovery of a new monomeric peptide that reduces body weight and diabetic complications in rodent models of obesity by acting as an agonist at three key metabolically-related peptide hormone receptors: glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP) and glucagon receptors. Such balanced unimolecular triple agonism proved superior to any existing dual coagonists and best-in-class monoagonists to reduce body weight, enhance glycemic control and reverse hepatic steatosis in relevant rodent models. We demonstrate that these individual constituent activities harmonize to govern the overall metabolic efficacy, which predominantly results from synergistic glucagon action to increase energy expenditure, GLP-1 action to reduce caloric intake and improve glucose control, and GIP action to potentiate the incretin effect and buffer against the diabetogenic effect of inherent glucagon activity.