In The Real Bathroom Scales, we verified two important facts. First, we confirmed that the body responds to alterations in calorie balance with a combination of adjustments to energy storage (body mass) and to energy usage, the latter being mostly via changes to TEF and NEAT. Second, we saw that there was a wide variance between individuals in their rate and degree of adaption via the energy expenditure variables. In fact, in the Mayo Clinic NEAT study, the change in expenditure in response to an added 1,000 calories per day ranged from a low of +107 cals to a high of +917 cals, a nine-fold difference!1 So what drives these vast differences in our ability to adapt to changes in intake, such that some of us pile on the pounds, while others never seem to gain an ounce?
While there are myriad biological abnormalities that can lead to obesity, most of them are uncommon, such as leptin deficiency, adrenal tumors, or genetic diseases such as Prader-Willi Syndrome. Most common obesities, on the other hand, can be directly linked to poor function or signaling of the sympathetic nervous system. The SNS is a primary regulator of many of the body’s homeostatic mechanisms, not the least of which is energy balance. The effects of the SNS on energy balance are achieved through the binding of catecholamines (adrenaline and noradrenaline) to a series of receptors known as the adrenergic receptors.
“Greek Alphabet Soup”
There are two basic types of adrenergic receptors, the alphas and the betas, and while both play a role in the management of body fat, the beta adrenergic receptors have been much more extensively studied with regard to energy balance, so we’ll start there. There are three beta receptors, and all are involved in the automatic regulation of energy expenditure, with some ability of each to compensate for the others. When these receptors are sufficiently stimulated by endogenous catecholamines or pharmacologic substitutes, the body is relatively resistant to weight gain. High levels of beta adrenergic stimulation probably underlie the “lean ‘n hungry” phenotype referred to in The Calculus of Calorie Counting. Without that stimulation, eating the same amount of food and doing the same amount of exercise, you will simply burn less of it as heat and energy and store more of it as fat. Like the patient in the Mayo Clinic NEAT study who only increased his energy expenditure by 107 calories per day, you would have what researchers call “defective thermogenesis”.
Although the concept of thermogenesis has been around for at least half a century, the definitive proof that the beta-adrenergic receptors mediate thermogenesis took some time to develop.
Adapted from “beta-AR Signaling Required for Diet-Induced Thermogenesis and Obesity Resistance” by Bachman, E.S., et. al. Science, August 2, 2002; 297(5582): 843 – 845.
While on the diet, the mutant mice maintained slightly lower blood glucose levels, despite secreting approximately half the amount of insulin as the controls. Because of the reduction in insulin, weight gain was significantly lower, too. After 10 weeks on the diet, the mutants had added 27% to their weight, while the wild-types gained 50%–all while eating and exercising in a similar fashion.
So here we have two common physiologic aberrations–insulin resistance and decreased adrenergc stimulation–that lead to decreased energy expenditure without any difference in diet or exercise patterns. For those who have any degree of either or both of these conditions, fat will tend to accumulate easily and be difficult to lose, while those on the other end of the spectrum, our (annoying) “lean ‘n hungry” friends, can’t gain weight to save their lives.
Now, the important thing is, is there anything we can do about this? Well, it just so happens there is. If nature left a little something out of your gene pool, you can get it back. In my next post, You Can Get There From Here, I’ll start showing you which products, both prescription and OTC, can truly change your metabolism.
- Levine, J.A., et. al. Role of Nonexercise Activity Thermogenesis. Science 1999; 283(5399): 212–214. ↩
- Price, L.H., et. al. Alpha 2-adrenergic receptor function in depression. The cortisol response to yohimbine. Arch Gen Psychiatry 1986 Sep; 43(9): 849-58 ↩
- Segal, K.R., et al. Independent Effects of Obesity and Insulin Resistance on Postprandial Thermogenesis in men. J Clin Invest 1992; 89:824-833. ↩
- Marette, A. and Bukowiecki, L. J. Stimulation of glucose transport by insulin and norepinephrine in isolated rat brown adipocytes. Am J Physiol Cell Physiol 1989; 257: C714-C721. ↩
Besides a flashback to a musical era I’d just as soon forget, the phrase “lean and hungry” has been used in obesity research to describe those naturally thin folks who have difficulty gaining weight, no matter how much they eat—much like Sims’ prisoners in 
As you can see, it appears that the leannest individuals actually eat the most. Even if you have doubts about self-reported intake, it’s pretty clear that weight is not proportional to consumption; that is, people who are 30, 40, or 50% above normal weight eat nowhere near 30, 40, or 50% more than their lean ‘n hungry counterparts. So how are variations in caloric intake actually dealt with by our bodies?
“A calorie is a calorie is a calorie…NOT!”
In 
Total energy intake was increased by 35%, from 2,824 to 3,824 kcal/day, while total energy expenditure increased by just over half that amount, from 2,824 to 3,350 (18.6%), by the end of the eight weeks. If the subjects were not exercising (a fact verified by accelerometer use), how did their daily energy expenditure increase? The measurement processes showed the following: REE increased 4.8% for a total of 79 calories, which is about what we’d expect from the increase in body mass. Calories attributable to TEF increased by an impressive 62%, moving from 218 to 354 calories per day. And the calories burned in Non-Exercise Activity Thermogenesis (NEAT), changed from 913 to 1,224 per day, an increase of 311 kcal, or 37%. Thus, TEE, after eight weeks of eating 1,000 additional calories, was automatically raised by the body to the tune of 527 calories per day, or 53% of the increase in intake—the equivalent of a 4-5 mile walk. To summarize:
What we’ve shown here is that the difference in people’s weights has precious little to do with how many cheeseburgers we eat or how many marathons we run, but rather much to do with energy expenditure variables we cannot voluntarily control—TEF and NEAT. All we have proven so far is that when our bodies sense a surfeit or deficit in energy supply, they attempt to balance it with changes to both energy storage and energy use, the relative percentages of which are highly variable between individuals. But what makes some folks more prone to the storage side and others more prone to “use”? We’ll explore that question in my next post, 
As an example, in 2006, researchers showed that the metabolic rate of mildly overweight people during non-movement sleep (a decent proxy for REE) decreased after just three months of a 25% calorie deficit, created through diet alone or diet + exercise. In the graph, you see sleep energy expenditure (SEE) predicted from baseline SEE and three-month LBM, compared to the actual three-month SEE. The difference is small, but significant: 7.7% for the diet-only group, and 4.9% for the diet+exercise group. The difference persisted over the next three months, when the subjects were fed the amount necessary to maintain the three-month loss.
In fact, many studies found that TEF was consistently higher in lean vs. overweight folks, which led to explorations of what else might be involved in TEF. In a series of elegantly designed experiments, Dr. Karen Segal and her team showed that insulin resistance and body fatness are independently and negatively associated with TEF. In this image, we can see that insulin-sensitive, lean persons burn considerably more calories in response to a given meal than do insulin-resistant or obese persons, matched for LBM and RMR. Clearly, there is much we have to learn from studying TEF, even if it is a relatively small portion of our daily TEE, and I’ll get into that more deeply in another post.
In a delightful study performed just down the road at UNC-Chapel Hill, a group of Sprague-Dawley rats (a strain of rat disinclined to high levels of activity) showed researchers what happens to NEAT when sudden changes are made in EEE. The scientists forced the rats to run on little rat treadmills for a specified distance and at a specified speed for the first three days of each week, then allowed them to rest the other four. This experiment went on for five weeks, and during the final week, spontaneous activity of the animals was measured during their non-exercise period and compared to matched controls. What the researchers discovered was quite fascinating. Spontaneous activity was greatly reduced on the three exercise days and modestly reduced on the four non-exercise days. That is, the forced increase in EEE was compensated for by an unconscious decrease in NEAT. Furthermore, following cessation of the experiment, there was a “persistent depression of spontaneous activity” for “a very considerable period of time”. The rats’ little bodies were battling back against the attempt to use a lot more energy than they were naturally designed for.
“The dieter’s playground”
So what is all this telling us? Well, the next time someone refers to weight loss dieting as a roller coaster, you can correct them—it’s not a roller coaster, or a merry-go-round, and it’s certainly not “The Fun House”. It’s more like a see-saw—the harder you push down on your end, the higher up you’re going to bounce when your body pushes back. In my next post, 
