Obesity and weight regulation

When last we left off, the subject was the food reward/palatability hypothesis of obesity and why I find it so unconvincing and problematic.

This post is going to address that issue by first discussing three new papers published on the subject of sugar.  Then I’m going to ask a lot of questions, hoping at least some of the answers will be obvious. All three papers are from Peter Havel and his collaborators at U.C. Davis and Vanderbilt; all three looked at the metabolic effect of the fructose-component of sugar, while one of them one also looked at the effect of sugar itself in the form of high fructose corn syrup (HFCS).

Paper number one describes an experiment in which rhesus monkeys were fed their usual monkey chow diet supplemented by a daily 300-calorie ration of fructose-sweetened water. After a year, every last one of the 29 monkeys had developed “insulin resistance and many features of metabolic syndrome, including central obesity, dyslipidemia and inflammation.” Four of the monkeys progressed to type 2 diabetes.

Worth noting is that the monkeys apparently drank all the fructose-sweetened drinks they were given, but they adjusted for the 300 additional calories by cutting back significantly on the chow. All in all, they averaged only 26 calories per day more with the fructose than they did without it. This suggests that the negative sequelae observed over the course of the year were indeed caused by the fructose itself and not an increased intake of total calories (unless we’re willing to accept that increasing calories by just a couple a dozen a day is sufficient to do some very bad things to monkeys and do them relatively quickly.)

The second and third papers, both published in October, were randomized controlled trials in humans — rather than primates or rodents — which is  always a nice attraction in nutrition research since there’s no guarantee any animal model really reflects the physiological situation in, well, us.

The second paper reported that overweight and obese older adults (40 to 72 years-old) getting a quarter of their calories from fructose-sweetened beverages used less fat for fuel and actually expended less energy than did the same subjects when they were getting the equivalent calories from glucose drinks. So the calories were the same; the metabolic effects were different. For the fructose, the effects were what we’d expect (okay, what I’d expect) if the fructose beverages were causing or exacerbating insulin resistance, an observation that Havel et al had published earlier. The more insulin resistant these people became, the less fat they used for fuel—hence, we can assume, the more fat they stored—and the lower their basal metabolic rate. (The rhesus monkeys, too, had decreased their energy expenditure in response to drinking fructose.)

The third study was a trial in younger subjects (18 to 40-year-olds), some lean, some not. These subjects were given three beverages to drink every day, constituting again about a quarter of their day’s ration of calories. The beverages were sweetened either with fructose, glucose or high fructose corn syrup. For the HFCS group, this 25 percent of calories was compatible with what the U.S. Dietary Guidelines considers a safe upper limit for sugar consumption. Still, after only 12 days—less than two weeks—subjects in both the HFCS and fructose groups, but not the glucose group, saw a significant increase in heart disease risk. Triglycerides went up; LDL cholesterol went up, and ApoB concentrations, a measure of the number of LDL particles, increased.

What can we take away from these studies? Well, these three papers certainly support the contention that the sugars consumed in western diets have very specific deleterious metabolic effects, and that maybe these sugars are the, or at least a proximate cause of insulin resistance and metabolic syndrome, and so, we can assume, obesity and type 2 diabetes and perhaps all the other chronic diseases that associate with these two conditions (cancer anyone?). This was the thesis of my April New York Times Magazine cover article “Is Sugar Toxic.” Here’s how Havel et al phrased this notion in the monkey paper:

The incidence and prevalence of insulin resistance and metabolic syndrome in the United States has increased dramatically over the past several years, and we and others have proposed that this increase may in part be attributable to increased consumption of fructose derived from dietary sugars, principally sucrose and high-fructose corn syrup (HFCS).

And, yes, the three papers certainly add fuel to this possible fire.

So on one hand, we can explain the metabolic abnormalities observed in these three studies—the insulin resistance, metabolic syndrome, raised triglycerides and increases in ApoB and LDL cholesterol—as all caused by the metabolism of the fructose in the liver in concert perhaps with the insulin-stimulating effects of glucose.  This is not a particularly controversial position. The sugar industry is not a fan, but research has consistently demonstrated these effects and has since the 1960s, and the biochemistry behind them is well understood.

So now we have three clear propositions and we’ll follow them up with the obvious question:

Proposition #1: The metabolism of fructose in large quantities by the liver results in a system-wide hormonal disruption — insulin resistance, in particular.

Proposition #2: Insulin resistance is intimately associated with obesity and is the underlying defect in type 2 diabetes.

Proposition #3: Insulin is the fundamental hormonal regulator of fat accumulation in fat cells.

Obvious question: Considering these three propositions, isn’t it likely that insulin resistance and the chronically elevated levels of insulin that go with it are causal factors in the obesity seen in the monkeys and, well, in humans who consume significant sugar, too?

This line of reasoning is one of the principle reasons that I’ve argued in my books and this blog that the carb/insulin hypothesis should be considered the null hypothesis of obesity, the one we believe until remarkable, unambiguous evidence comes along to refute it.

We have a disorder, obesity, that associates with a host of chronic diseases of western diets, all of which are associated as well with metabolic syndrome – i.e.,  insulin resistance — and type 2 diabetes. So if insulin plays a major role in regulating fat accumulation in individual fat cells, which is not a point of controversy, and if dysregulation of insulin signaling is a major component if not the causal factor in the diseases that associate with obesity, also not particularly controversial, it seems like a very good assumption that obesity, too, is caused by a the same dysregulation in insulin signaling.

Now the salient questions are these: How remarkable and unambiguous does the evidence have to be before we toss all this out in favor of the idea that we get fat because rewarding foods stimulate neurochemical changes in brain centers that raise our adiposity set point and ultimately make us eat more than we expend? And what do we gain by doing it?

I will argue that tossing out the role of insulin on fat accumulation to embrace the idea that rewarding foods stimulate brain centers seems inherently foolish, because the evidence is by no means unambiguous and in the process we disassociate weight gain from all these other insulin-mediated and very closely related disorders.

Let’s first try to address this cost-benefit ratio — what we gain from the food reward/palatability hypothesis compared to what we lose — by narrowing our scope to the three sugar papers from Havel’s group. We want to answer these two questions: 1). what does the food reward/palatability hypothesis of obesity add to our understanding of the fructose-related effects documented in these papers? 2). Is it a valuable addition?

As I said, few of us, if any, would doubt that sugar-sweetened beverages (SSBs, as they’re now fashionably known) or fructose-sweetened beverages have a high-food reward value. The monkeys seemed content to drink all their 300 calories-a-day of fructose, and to do so at the expense of other more nourishing food (the chow). Put simply, they apparently found the fructose more rewarding. Havel told me when I interviewed him for the NYT Magazine article that they had difficulty finding any of the younger (human) subjects for their experiments who didn’t already drink at least two daily sugar-sweetened beverages, and quite a few were drinking six.

So it’s certainly a reasonable assumption that SSBs are hyper-rewarding, among the low-hanging fruit in the food reward/palatability world, as , as Dr. Guyenet of Whole Health Source has categorized them in his posts on this subject. Easy targets in other words—indisputably rewarding.

Now these highly rewarding beverages are given in a randomized-controlled trial to human subjects, as Havel and colleagues did, and the amount given is fixed.  They’re given daily to monkeys as part of their dietary regimen, as Havel and colleagues did, again a fixed amount. In both species, they cause the metabolic/hormonal effects we would expect on the basis of a few decades of biochemical and endocrinological research on insulin and on the metabolism of fructose in the liver.

So now we’re going to take a leap of faith and assume that the hyper-rewarding nature of these beverages explains why the monkeys got fatter drinking them, and maybe the humans, too, if any of them did indeed gain fat in such a short period on the beverages, but what about the metabolic and hormonal effects observed?  Does the fact that SSBs have a high food reward/palatability value tell us anything meaningful about why these sugar- or fructose-sweetened beverages cause peripheral effects in addition to increased adiposity—insulin resistance, metabolic syndrome, type 2 diabetes, raised triglycerides and ApoB number, etc.?

Here’s another way to phrase that same question: If consuming these different sugar waters have very well-specified effects in the body (peripheral effects, as they’re known in the lingo), and these effects are sufficient to explain all the observations – increases in adiposity, insulin resistance, dyslipidemia, type 2 diabetes, etc. — why evoke a couple of arguably vague concepts like food reward and palatability to explain one of them alone, the increase in adiposity?

Let’s agree for the moment, that it’s worth it. We’re going to accept this hypothesis because it’s just right and the carbohydrate/insulin hypothesis is not. It’s the hyper-rewarding nature of sugar- and fructose-sweetened beverages causes fat accumulation, as seen in the monkeys in paper number one, and in free-living humans drinking SSBs. If we decide this reward value thing is at least a major contributor, we’re still stuck with having to explain the metabolic and hormonal disorders. We can’t just ignore those, so we have to complicate the hypothesis to do so — add epicycles, as historians or philosophers of science would put it. We have to explain how these SSBs also cause insulin resistance and metabolic syndrome, why they raise triglycerides and LDL cholesterol and ApoB etc..

Researchers who study obesity and insulin resistance have been confronted with this same problem since the early 1960s, once they decided that obesity had to be caused by taking in more calories than we expend. The way they’ve traditionally done it is to say that we get fatter because we take in more calories than we expend, and then we get insulin resistant because we are getting fatter. Two different mechanisms.

This rationale can help proponents of the food reward/palatability hypothesis out of the same hole. In this case, blame the excess fat accumulation on the hyper-rewarding nature of sugar and the neurochemical effects it induces in the brain; this raises set point and so we eat more than we did and get fatter. Then we can blame the insulin resistance and all that goes with it on the process of getting fatter.

Not too bad, but then we have to explain why the same metabolic effects happen in individuals who remain lean, who do not accumulate the offending fat, and we can’t, or at least not without adding yet another mechanism (another epicycle) for the lean people. Because lean people can also be insulin resistant and dyslipidemic and get type 2 diabetes and all the associated chronic diseases. So one way or the other (or so it seems to me), we need our knowledge of the peripheral effects of sugar consumption – the metabolic and hormonal effects in the liver, the pancreas and other organs – to understand at least some of the observations, if not all of them.

In its current form, the palatability/food reward hypothesis explains only fat accumulation. It explains why the monkeys gained weight, and I guess why we do too when we drink a lot of sugared beverages, but it offers no explanation for the the metabolic consequences that accompany the weight gain, both in the studies discussed and in real life.

Here’s yet another question to always keep in mind when thinking about the food reward/palatability hypothesis of obesity: Do we gain anything from it other than the obvious: that if these foods weren’t highly rewarding or palatable, we probably wouldn’t eat them, or at least not enough of them to make us fat and cause the deleterious metabolic effects?

And even if we do gain something meaningful from acknowledging that the food reward/palatability value of foods causes us to consume more of them, this benefit to our understanding would still come with a very important caveat: Maybe the reason these foods have a high reward value or are so palatable is because of the metabolic and hormonal effects of eating them. Maybe a food that can cause insulin resistance or hyperinsulinemia can also cause us, through its various peripheral effects, to crave it more, to find it more rewarding.

Anything’s possible, and this is one hypothesis, a very important one, we should always keep in mind. And it’s one I’ll return to shortly, or at least shortly by my standards—i.e., over a few more posts and several thousand words more words.

(And when I’m done with these food reward hypothesis posts, I’ll get to the evidence against the insulin hypothesis. Lord knows when that will be, but I’ll get there.)

When last I posted, oh so long ago, I promised next to discuss the food reward/palatability hypothesis of obesity and why I find it so uncompelling and more than a little bit disheartening.  Why, in effect, I think it is the kind of bad science that begs to be challenged, as I did, when it is presented in a public forum, as Dr. Stephan Guyenet of Whole Health Source did at the Ancestral Health Symposium back in August. This is the first of five posts to address this and I promise (really) that it will be days between posts, not months.

Here’s how Dr. Guyenet describes his hypothesis in his sixth of an increasing number of blog posts on food reward:

…The evidence as a whole shows that chronic consumption of foods with an excessive reward value causes abnormalities in parts of the brain that regulate body fatness, metabolism and reward/motivation.  This can lead to weight gain and metabolic problems, and favor addictive and compulsive relationships to food and other things.  The combination of readily accessible, cheap, high-reward food, and stressful lifestyles that drive us to eat it, is probably a major contributor to overweight, obesity, diabetes and perhaps other health problems in affluent nations.

What makes this hypothesis novel is that the ability of a particular food to make us fat — what makes a food fattening, in effect — is mediated, according to Dr. Guyenet, through its ability to stimulate neurochemical effects in the brain.

So why do I find this intriguing idea objectionable, so objectionable, in fact, that I was willing to stand up at the AHS and make a bit of spectacle of myself? Well, for starters, the food reward/palatability hypothesis  can’t explain the kinds of observations about obesity and weight regulation that I’ve been arguing in my books must  be explained by any viable hypothesis of why we get fat. This is the primary issue, obviously, as a hypothesis that can’t explain the necessary observations is a failed hypothesis. And we’ll get to this issue in the posts to come.

The lesser reason for my objections, and the subject of this post, is that this hypothesis seems to be yet another thinly-veiled variation on the energy balance paradigm of obesity — calories-in, calories-out — and I’ve been arguing that this particular paradigm is fatally misguided in a variety of different ways. I believe that obesity researchers will never make meaningful progress until they rid themselves of this belief system, and that so long as they hold onto it they’ll be effectively blaming the obese for the problem of their obesity. Hence, finding yet a new way to embrace it, or popularizing an old way, as Dr. Guyenet has, seems to be a step in precisely the wrong direction.

Ultimately, this comes down to what I consider the two competing obesity paradigms or belief systems.

Competing paradigms: 1. body rules

One is a body-rules paradigm and I’ve been arguing that it’s the only one that can do a reasonable job of explaining all the meaningful observations. Changes in the hormonal and enzymatic regulation of fat metabolism—in the regulation of fat storage and oxidation—drive changes in adiposity; and changes in adiposity drive compensatory changes in intake and expenditure.

Here, the body is running things. Indeed the organ in control may be the fat tissue itself in concert with the liver. The University of Vienna endocrinologist/geneticist Julius Bauer described this fat-rules concept back in 1929 by saying that  the fat tissue of someone who’s obese (what he called “abnormal lipophilic tissue) “maintains its stock, and may increase it independent of the requirements of the organism. A sort of anarchy exists; the adipose tissue lives for itself and does not fit into the precisely regulated management of the whole organism.”

In this scenario, the brain plays no more role in regulating the growth of the fat tissue than it would regulating the growth of any tissue — a tumor, for instance, which is a metaphor that Bauer uses, or the growth of fat tissue in breasts and hips and butt when a young girl goes through puberty, or the fat put on by a mother-to-be when she is pregnant, another Bauer metaphor, or just the growth of lean and fat tissue in children as they develop and mature.

In all these cases, the body is doing its own thing, more or less independent of the brain’s input, even though the brain, in the case of growing children, is the source of the growth hormone that is driving the growth. More energy has to be taken in than expended while growth is occurring (at least by the tissue itself, if not the whole body), but that “positive energy balance” — calories in greater than calories out — is a compensatory effect of the growth; it’s not a cause.  The brain does what it always does, which is reacting and modulating homeostasis in response to environmental signals. But it’s a secondary organ in this sense.

In this paradigm, specific foods are fattening because they induce metabolic and hormonal responses in the body — in the periphery, as its known in the lingo — that in turn induce fat cells to accumulate fat. The brain has little say in the matter. As I describe it in my books (and as it was described to me by the few researchers today who hold this view), we don’t get fat because we overeat; we overeat because we’re getting fat. 

If we come to crave specific foods or find them more rewarding than others and these foods are fattening — not necessarily the same thing — then we likely do so because of their physiologic effects, the changes in the hormonal milieu of the body caused by the consumption of these foods. Foods that make us fat come to be foods we crave, because these foods are also the foods that make us hungry. So how much we might like a food or how rewarding we might find it or how much we might crave it are primarily consequences of the peripheral metabolic/hormonal effects.

In this paradigm, meals stimulate hormonal responses—insulin, in particular, either in the short term (glucose) or the long term (fructose)— and this in turn directly influences both the storage of fat and the oxidation of fatty acids elsewhere in the body. The balance of forces working on the fat tissue, a dynamic equilibrium, ultimately determines how much fat we accumulate. As fat accumulation increases, so does secretion of leptin and other adipokines that work in a variety of feedback loops in the brain and the body (as does insulin itself) to ideally prevent excessive fat accumulation.

This body-rules hypothesis, of course, isn’t the conventional wisdom. If it were, I would be doing something else with my career.

Competing paradigms: 2. brain rules

The conventional wisdom is that we get fat because we take in more calories than we expend. Simple enough. We get fat because we overeat, not the other way around. Changes in energy balance—calories-in minus calories-out—drive changes in adiposity, in how much fat we carry around in our fat cells.

Ultimately, as I discuss in Why We Get Fat, this is a brain-rules paradigm. After all, both the components of overeating — eating too much, aka gluttony, or moving too little, aka sloth — are both behaviors and in this paradigm behaviors are psychological phenomena not physiological.

Researchers who live in this paradigm are invariably trying to discover what’s wrong with our brains or the signaling to our brains that cause this particularly cherished organ (what Woody Allen memorably described as his “second favorite organ”) to screw up. Why can’t the brains of people who become obese or overweight get the energy balance thing right? Or why do these brains effectively desire more fat on the body than is healthy? Why do they set the “set point” of adiposity too high? The problem with people who get obese is in their brains, not their bodies (even though the excess fat is in the body).

In this paradigm, the fat tissue is more or less passively following the brain’s lead. Meals will stimulate a variety of gut hormones and fat-derived hormones like leptin, grhelin, etc., and these in turn signal the brain whether to continue eating or not, whether to act on hunger or satiation, and perhaps how much energy to drive the body to expend. But ultimately the deciding factor on whether a person gets fatter or leaner is the balance of energy expended or consumed—calories-in minus calories-out—and this is regulated by the brain. The fat tissue’s say in the matter is mostly relegated to its secretion of leptin and other adipokines, as these fat-derived hormones are known, that might in turn work in the brain to curb hunger or maybe work in the body to increase expenditure. Energy balance, though, drives adiposity and energy balance (energy homeostasis, as its often called) is ultimately a brain thing not a body thing.

The twist that the food reward/palatability hypothesis of obesity gives to this energy balance paradigm is to make the meaningful effect of a fattening food that of changing the neurochemical balance in the brain. This in turn changes set point and adiposity increases (or decreases) in response. This scenario can appear to be one that rejects, as I do, the simplistic calories-in-calories-out idea, but I’m going to argue that this appearance is an illusion. And that, as I said, is one reason why the hypothesis irks me so.

Here’s one way to look at these two competing paradigms, now with the food reward/palatability hypothesis of obesity standing in for the conventional wisdom:

Here’s the fat-rules paradigm: We’re not getting fat because we are overeating; we are overeating because we’re getting fat—because a hormonal disorder, caused by the consumption of certain foods (refined grains, easily-digestible starches and sugars) drives us to accumulate fat in our fat tissue. 

And here’s the food reward/palatability hypothesis, a brain-rules hypothesis: We’re not getting fat because we are overeating; we are overeating because our brains are driving us to get fat—because a neurochemical disorder, caused by the consumption of certain foods (refined grains and sugars, as well as fats and salty foods and industrially processed foods of other types as well), in turn drives us to accumulate fat in our fat tissue. 

So you can see how confusing this can be, how similar these two hypotheses can appear. But the question ultimately is how does the brain go about increasing fat accumulation in the food reward/palatability hypothesis. What do these neurochemical changes do to the brain and then what does the brain do that ultimately leads to more fat in the fat cells, which are, after all, mostly half-a-body or so away? What’s ultimately driving the fat?

Here’s where the food reward/palatability hypothesis seems to collapse back down to just another failed twist on calories-in-calories-out. It’s yet another attempt to explain why fat people get fat, and why it’s caused by eating too much (or exercising too little), without explicitly blaming obese or overweight individuals for not being able to control their behaviors (as we lean people do). Chapter 7 in Why We Get Fat goes into this problem in detail.

(A caveat here: I’m willing to be convinced that this hypothesis is not an energy balance hypothesis, and so not a brain-rules-and-the-fat-passively-follows notion, but so far I haven’t seen an argument that’s convincing. I confess, though, that I find the hypothesis surprisingly difficult to understand, which suggests that either I’m losing my intellectual facilities in my dotage — always possible — or that I’m so blinded by my love of my own hypothesis that I refuse to understand it—at least equally likely — or maybe, just maybe, that Dr. Guyenet and other proponents of the hypothesis don’t really understand it either.)

The food reward/palatability hypothesis: looking for a mechanism

As Dr. Guyenet says, as I quoted above, the chain of causality in this hypothesis goes like this: “abnormalities in parts of the brain that regulate body fatness, metabolism and reward/motivation… can lead to weight gain and metabolic problems…” But he doesn’t say how. How do abnormalities in parts of the brain lead to weight gain? The answer seems to be that the brain raises our adiposity set point, but then how does that actually make us fatter? Now we have a change in the brain — set point has gone up — but we still have to explain the change in the body — adiposity increases. How does that happen?

And the answer is that the brain affects this change in fat mass, as proponents of the hypothesis seem to see it (or seem to see it most often), by either increasing food consumption or decreasing expenditure. So the brain is regulating the fat mass not by regulating fat accumulation directly, but by making us eat more and maybe expend less — calories-in-calories-out. And fat people get fat not because their fat tissue is living for itself, as Bauer put it, and increasing its stock of fat, independent of the nutritional state of the organism, but because fat people either respond to rewarding foods differently than lean people do or because they can’t resist this drive to eat more food once their set point goes up. Lean people either can resist the urge, or the rewarding foods don’t have the same neurochemical effects in their brains.  Either way, the brains of lean people are more resistant to fattening foods (those with high food reward/palatability value) than the brains of fat people, and the body, in either case, is kind of irrelevant.

Now, the brain could regulate fat mass directly by increasing, for instance, insulin secretion via increased stimulation of the vagus nerve, but Dr. Guyenet would like to dismiss the role of insulin in excess fat accumulation. (This is another post I’ve promised in my last post and one that might come along, well, maybe in a month or two, after we’re done with these food reward posts). As a result, this particular mechanism is not apparently part of the hypothesis.

When I asked Dr. Guyenet, shortly after my last post, why he believed so strongly that the food reward hypothesis was not an energy balance idea, he suggested that I could significantly improve my understanding of this issue by reading his current mentor Michael Schwartz’s 2006 review article in Nature – “Central nervous system control of food intake and body weight.”

A lengthy but not necessarily irrelevant digression

Curiously enough, I had a run-in with Professor Schwartz himself over precisely this issue back in March 2005 when I was reporting Good Calories, Bad Calories. Schwartz built his reputation in obesity research in part by demonstrating that insulin in the brain suppresses food intake – or at least that it does when it is injected directly into the cerebral spinal fluid of baboons. He then argued that this is the hormone’s primary role; Dr. Guyenet is now making very similar arguments. In their opinion, what happens in the brain trumps what happens in the body. Schwartz has actually suggested that one reason for the obesity epidemic may be that we’re not secreting enough insulin because we’re not eating enough carbohydrates. Dr. Guyenet does not go that far.

I argued in an e-mail exchange with Schwartz that because insulin is secreted in the periphery, and that because it can be shown in both humans and animals that increasing insulin in the periphery increases fat accumulation, this would seem to be the primary effect. The appetite-suppression effect in the brain, therefore, would be a secondary effect—a negative feedback loop of the kind that you would expect to see in a homeostatic system.

Schwartz took exception to being questioned by a journalist and he argued that the role of journalists in this field was that of  “helping to debunk profit-motivated, unscientific views that are so prevalent in our culture.” I took exception to being told what my journalistic role should be and replied that my role was to help debunk unscientific views prevalent in our culture, regardless of their institutional provenance or apparent motivation. It took us several e-mails back and forth to achieve a peaceful co-existence again.

Back on track:  the mechanism of food reward/palatability

The Schwartz article that Dr. Guyenet suggest I study, though, makes it relatively clear that the food reward/palatability hypothesis of obesity is indeed firmly entrenched in the energy balance paradigm. (I pointed this out to Dr. Guyenet in an e-mail, and he said he would get back to me on it. Apparently other concerns interceded on his side, though, and so I write this without benefit of his clarification.) “Through a process known as energy homeostasis,” Schwarz and his co-author write, “food intake is adjusted over time so as to promote stability in the amount of body fuel stored as fat.”  And energy homeostasis, they explain, is regulated via a negative feedback model:

Introduced more than 50 years ago, the `adiposity negative-feedback’ model of energy homeostasis is founded on the premise that circulating signals inform the brain of changes in body fat mass and that in response to this input, the brain mounts adaptive adjustments of energy balance to stabilize fat stores.

So the brain adjusts energy balance (intake and expenditure) to stabilize fat stores; the brain rules, we eat  more or expend less, and the fat tissue inflates or deflates accordingly. And this is why Dr. Guyenet and others can write thousands of words about food reward and palatability without ever actually discussing the hormonal/enzymatic regulation of the fat tissue itself, which is, after all, the ultimate organ of interest, and without discussing the hormonal/metabolic regulation of fatty acid oxidation in the lean tissue, when it’s the fatty acids that are ultimately being stored.

The alternative would be to suggest that the brain adjusts fat stores directly via hormonal and central nervous system mechanisms, and this leads to compensatory changes in energy balance. But then, as I said, we would have to discuss the direct peripheral effect of insulin on fat storage and fatty acid oxidation, and that’s not allowed.

“Obesity, by definition, results from ingesting calories in excess of ongoing requirements,” Schwartz and his co-author write, and I’m arguing that any researcher who makes this statement for any reason other than to make the point that it’s meaningless and misleading is living and working in an energy balance paradigm — calories-in, calories-out.

And because I think the energy balance paradigm of obesity is more or less the root of all scientific evil in this business — not just because it’s taken obesity researchers down a century-long blind alley, but because of its implications that fat people just can’t control their urges the way lean people do — I find Dr. Guyenet’s promotion of this hypothesis and its acceptance, limited as it may be, in the paleo and low-carb blogospheres to be very disheartening. I could be wrong (of course) about the scientific bankruptcy of this hypothesis, but I’m going to argue (of course) that I’m not.

In my next post—just a few days from now, I promise (barring extenuating circumstances like the Hayward fault underlying our neighborhood deciding to go off with a magnitude significantly higher than the 3 to 4s we’ve been getting for the past two weeks) — we’ll continue this discussion by looking at the other major limitations of this hypothesis, beginning with some recent observations that it can’t seem to explain.