A recent obesity study is quite interesting because it looks at the peripheral impact and benefit of exercise, that is, physiological mechanisms in the body (peripherally) as opposed to those controlled by the brain (centrally). Warning: I don’t believe that the peripheral aspect of bodily function is really all that key to weight loss.
- Di Meo Sergio, Iossa Susanna, Venditti Paola. Improvement of obesity-linked skeletal muscle insulin resistance by strength and endurance training. J Endocrinol. September 2017;234(3):R159-R181. doi:10.1530/JOE-17-0186.
Obesity-linked insulin resistance is mainly due to fatty acid overload in non-adipose tissues, particularly skeletal muscle and liver, where it results in high production of reactive oxygen species and mitochondrial dysfunction. Accumulating evidence indicates that resistance and endurance training alone and in combination can counteract the harmful effects of obesity increasing insulin sensitivity, thus preventing diabetes. This review focuses on the mechanisms underlying the exercise role in opposing skeletal muscle insulin resistance-linked metabolic dysfunction. It is apparent that exercise acts through two mechanisms: it stimulates glucose transport by activating an insulin-independent pathway and it protects against mitochondrial dysfunction-induced insulin resistance by increasing muscle antioxidant defenses and mitochondrial biogenesis.
Early on, this article dives deeply into the peripheral mechanism of obesity. That review is quite thorough and also clarifies why most of the diabetes research is a waste of time clinically. Such researchers keep trying to figure out what the etiology of obesity is by looking at what the peripheral changes are. It’s pretty clear that the human has very little control and very little ability to control the periphery. So, that instills a focus on drugs to change the periphery, from insulin to all kinds of other interventions. Yet, from my recent experience, we are losing the battle against diabetes. Like cancer, we need more money and more research right?
But, if you take a behavioral approach, a peripheral emphasis is meaningless. Thus, we (behavioral-focused people) often emphasize the central nervous system (CNS). If you look at the success of the weight-loss combination of bupropion and naltrexone in dealing with cravings, it shows that a central mechanism is more intelligent and effective.
The other parts of the article continue to point out that the user has no control over peripheral events related to obesity and diabetes when it looks at genetic factors. However exciting the literature is in terms of understanding the genetics of insulin resistance, basically it’s meaningless from the patient perspective since changing insulin resistance is not something they can do.
They review all the data to date and show, yet again, that medications don’t impact weight loss much. We are left with coming up with some way of fiddling with gene expression as the real hope. This is a dead-end.
A Central Approach
More significant (and terrifying to pharma greed) is the finding that the central approach doesn’t need a drug. Similarly, data on the effectiveness of psychotherapy matches the effectiveness of medication, but without the side effects. That is, without the side effect of high cost (because society pays for pills, but not therapy). That side effect profile is good news to pharma companies that sell anti-depressants.
Essentially, the approach to diabetes can be addressed behaviorally through non-intervention with pharmaceutical agents and at a lower cost. So, it is key to kill the concept that such a strategy will work. And you need to make sure NIDDK only funds that kind of research – the “scientific” kind.
But It Is Worse – The Brain Works Against You!
The other point always missed in all of this is that it’s possible we ignore the reality that the brain has a positive and negative role. And, generally, its role is negative in that it provides countermeasures to all of our peripheral interventions. That is, our emphasis on a peripheral solution to fat absorption or glucose excretion or manipulation of human beings doesn’t recognize the potential of eating more and exercising less actually worsens the problem. We push the stone and the stone gets heavier. See how hard it is to recognize a changing condition? We like to believe that change happens in a world where everything stays the same. But, things don’t stay the same. And as we starve people (or use medications to extract glucose by having them excrete it in their urine or not absorb fat), they change their behavior to counter that.
The result is that obesity-related medications plateau and achieve a minimal impact in contrast to other medications like antidepressants or antibiotics, which tend to improve over time. The brain vs. periphery issue explains the failure of interventions to work over time, from surgery to basically everything else. By ignoring behavioral interventions we ignore the reality that the human brain is ready to counter any benefit.
The take-home point is that almost all obesity interventions ignore the brain, and this ignorance is why we consistently see the curve of patients’ weight loss plateauing and then patients regaining the weight if the intervention is removed. Time is working against peripheral interventions, even for weight-loss surgery.
