Has science found a way to overcome one of the most mysterious – and frustrating – challenges facing those seeking weight loss?
It’s a frustration expressed by millions of “losers” around the world.
After losing weight, why does it so often find its way back?
Conventional wisdom says people often get less compliant with their eating plans, allowing more calories and non-supportive foods to make their way back into their diets.
Conventional wisdom also says people become less compliant and consistent with exercise programs, perhaps not exercising as often or as intensely as during peak weight loss.
Conventional wisdom also suggests that some people simply give up, that the burden of maintaining healthy eating habits and frequent physical activity becomes too much for them.
If current science is right, conventional wisdom may not be so wise.
According to Gregory Steinberg, Canada Research Chair in Metabolism and Obesity at McMaster University, “It’s not that people just give up. We know people are good at losing weight with diet and exercise.”
If what Steinberg says is true, what’s the real problem? Just keep going with your caloric reduction (you know, the paleo-keto-whole30-lowcarb-lowfat-vegetarian-vegan-rawfood-macrobiotic) diet and keep up your exercise and the weight should keep coming off and stay off, right?
Wrong! The struggle is real for millions. They drop a bunch of weight and poof! It stops on a dime and often returns with a vengeance!
Wait! You didn’t KNOW that all successful weight loss diets work the same way, via caloric deficit? Huh…more on that reality of weight loss another time. For now, back to the cool science.
The problem is metabolism and body physiology. After losing weight, the body simply requires fewer calories.
Says Steinberg, “Quickly you hit a plateau at 5 to 10 percent weight loss and you can’t lose more weight than that because your metabolism slows down too much. This explains why relapse weight gain is so high.”
Why does the body’s calorie-burning capacity fall off after weight loss? It’s never been explained.
The accepted theory is that something stifles the body’s fat burning systems. The brain and hormonal systems work to reduce the metabolic rate, thereby reducing calorie and fat expenditures both at rest and, to a lesser degree, while active. Luckily, there are some pretty sharp folks working on figuring out what those things are.
One possible answer is being pursued by Ann Marie Schmidt and her team at NYU School of Medicine. She published a paper in Cell Reports last week about her study.
Schmidt is looking at a receptor on fat cells that appears to interfere with the weight loss function. In the mouse model she created, mice without any of this specific type of receptor didn’t gain weight even when they were consistently overfed.
Of her work, Schmidt said “When you delete (the receptor) it completely resets their metabolic program so that they are resistant to the diet-induced obesity. It’s totally unexpected and it has so many implications for human health.”
The receptor in question is the receptor for advanced glycation end products, or RAGE for short. Very appropriate, since I’m sure lots of people who gain rebound weight feel exactly that. But I digress…
Glycation happens when a molecule of sugar like glucose, fructose or galactose binds to a protein or lipid (fat) molecule without the mediating or controlling action of an enzyme. It’s also called non-enzymatic glycosylation.
Glycation in the human bloodstream leads to the production of advanced glycation end products, or AGE’s. Some of these are highly reactive molecules that have been associated with a number of age-related chronic diseases like cardiovascular disease, Alzheimer’s (amyloid proteins are by-products of the reactions leading to AGE’s,) peripheral neuropathy, sensory losses and even cancer. (1, 2)
While human and murine biology isn’t an exact match, RAGE receptors are found in a variety of both human and mouse cells, making it more likely the connection in mice also exists in humans.
If we target this receptor properly, then, we fix the weight loss plateau problem, right? Make a new drug, pump ourselves full of it and the weight falls off like dust. Not so fast, there, slick.
While it may be possible to target the receptor with drugs to make it stop stifling weight loss, as Schmidt says, “The puzzle has a lot more pieces to be worked out, for sure.”
McMaster’s Steinberg and his team had a breakthrough several years ago along the same lines. They discovered another system that seems to put a lid on fat burning via a mechanism involving serotonin. This one seems to prevent the body’s brown fat from burning more energy.
What is brown fat, you ask? While you can expect more from me on brown and white fat, what they do and what makes them different (and important,) for now I’ll give you the short explanation.
White adipose tissue (white fat) makes you fat. It’s the fat largely responsible for obesity and all the bad stuff associated with it. Okay, the fat itself isn’t responsible for all the metabolic diseases and problems. But having too much of it certainly leads to big problems.
Brown adipose tissue (brown fat,) on the other hand, has been linked with a lower BMI. (3) Brown fat has also been shown to have profound effects on body weight, energy balance and glucose metabolism. (4, 5, 6)
Brown fat has also been shown to protect against diet-induced obesity and diabetes. (4, 7) Hooray for brown fat, then, right? Maybe.
For a long time, the medical experts believed that humans had brown fat as infants but lost it as they grew into adulthood. Too bad for us, or so we thought.
Researchers using positron-emitting tomographic scans (PET scans) on adults with cancer noticed something interesting and not cancer-related. They found areas of metabolically active brown fat in the cervical-superclavicular regions of their human patients. This demonstrated the persistence of brown adipose tissue into adulthood.
Biopsies proved the existence of a unique protein found in brown fat in mice. The protein helps maintain body temperature and allows the mice to survive cold temperatures.
The discovery of brown adipose tissue in humans has spurred researchers all over to look for other similar mechanisms that might stifle calorie burning and weight loss. An entire new field of research is earnestly trying to figure out how we can burn more calories and conquer weight loss.
Obesity is quite complex. There are numerous factors involved, many of which are not purely X’s and O’s. Stress, emotion, hormones, the brain, food quality and quantity and a hundred other factors impact weight gain and loss and must be taken into consideration on at least a cursory level.
If scientists are able to create drugs to overcome the mechanisms that short-circuit fat-burning, calorie burning and weight loss, that might represent the “magic bullet” for which so many dieters and folks trying to lose fat are praying.
To date the road to that magic bullet has been paved with lots of snake oil, false hopes, fad diets and plenty of BS. With this discovery, it’s very possible that therapeutic treatments for the down-regulation of metabolism that occurs after weight loss might actually happen.
Needless to say, whoever makes that happen is likely to have some instant fans.
Keep the faith and keep after it!
1. Münch, Gerald; et al. (27 February 1997). “Influence of advanced glycation end-products and AGE-inhibitors on nucleation-dependent polymerization of β-amyloid peptide”. Biochimica et Biophysica Acta. – Molecular Basis of Disease
2. Munch, G; Deuther-Conrad W; Gasic-Milenkovic J. (2002). “Glycoxidative stress creates a vicious cycle of neurodegeneration in Alzheimer’s disease–a target for neuroprotective treatment strategies?”. Journal of Neural Transmission. Supplementa
3. Cohade C, Osman M, Pannu HK, Wahl RL. Uptake in supraclavicular area fat (“USA-Fat”): description on 18F-FDG PET/CT. Journal of Nuclear Medicine 2003
4. Cannon B, Nedergaard J. Brown adipose tissue: function and physiological significance. Physiological Reviews 2004
5. Himms-Hagen J. Obesity may be due to a malfunctioning of brown fat. Canadian Medical Association Journal 1979
6. Lowell BB, Flier JS. Brown adipose tissue, beta 3-adrenergic receptors, and obesity. Annual Review of Medicine 1997
7. Cinti S. The adipose organ. Prostaglandins Leukot Essent Fatty Acids 2005