Category Archives: gastric bypass

The Laws of Energy Balance FTW!

Weight loss maintenance is not determined by calorie intake… or physical activity… but by The Laws of Energy Balance FTW!!!

Odd, the sensation I felt when reading this news release (gloating?).  As reported at a meeting of the Obesity Society, results from the Utah Obesity Study of gastric bypass patients 2 and 6 years after surgery.  By the 2 year mark, they lost over 100 pounds, or 36% of their starting weight (went from 296 to 189 pounds).  Energy expenditure declined from 2201 to 1736 kcal/day.  Food intake went from 2085 to 1638 kcal/day.  (Hint: it’s no coincidence that energy expenditure and food intake declined to the exact same degree.)  Physical activity and fitness levels increased.

By the 6 year mark, they still weighed 29% less than their starting weight.  N.B. that’s an amazing level of success, it’s virtually unheard of in diet intervention studies.  +1 for gastric bypass; -1 for nutrition.

Here’s what piqued my interest: during the gradual increase from 189 pounds to 210 pounds, which occurred between years 2 and 6 post-surgery, the most significant factor associated with weight regain was not calorie intake or physical activity… it was metabolic rate.  This represents another fail for “eat less move more,” and a win for the Laws of Energy Balance.

So what’s this got to do with The poor, misunderstood calorie?

what we know about metabolic rate:

1)      It’s invisible.

2)      Fructose vs. The Laws of Energy Balance (circa December, 2011): sugar-sweetened beverages can cause fat gain, not by providing excess calories, but by reducing metabolic rate.

3)      Holiday feasts, the freshman 15, and damage control (circa January 2012): overeating a high protein diet causes less fat gain than overeating anything else because it increases metabolic rate.

4)      Missing: 300 kilocalories (circa July 2012):  after losing weight, subjects assigned to the low carb diet maintained a higher metabolic rate than those on an isocaloric low fat diet.

“Eat less move more” is not the answer.  But eating less sugar, more protein, and fewer carbs might be.  Nutrition matters.

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Yo-yo dieting revisited, a thought experiment

If at first you do not succeed, try, try again.  Opus 94.

Yo-yo dieting is “probably” not good, but giving up is worse IMO.  I say “probably” because obesity researchers have empirically tested just about every single weight loss intervention except this one.  Furthermore, you’d be hard pressed to find an obese population who’d agree to undergo an intensive weight loss regimen, only to intentionally regain the weight.  Rinse.  Repeat.  The study would be a nightmare to design from a philosophical perspective, and psychological torture to the volunteers.  But what if they did?  Would they end up with more fat mass?  Less?  Right back to where they began?

Changes in energy expenditure resulting from altered body weight (Leibel, Rosenbaum, and Hirsch, 1995)

Maybe you don’t recognize the study by name, but you have definitely heard about their key finding: weight loss causes a decline in metabolic rate which makes further weight loss or simply maintaining more difficult.  The other finding was that the opposite also occurs: during weight gain, metabolic rate increases to drive weight back down to its starting point.


All-in-all this was a great experiment and it has a lot of street cred; nobody including myself has ever had anything really bad to say about it.  In brief, volunteers were fed either: 1) the maximally tolerated amount of self-selected foods (~6500 kcal!) until they gained 10% of their body weight; or 2) 800 kcal of a liquid formula (40% fat, 45% carbs, and 15% protein) until they lost 10% of their body weight.  

When lean subjects gain 10% of their initial body weight, 80.1% of it is fat mass.  In obese subjects, however, only 58% is fat mass.  Thus, obese people gain more muscle and less fat than lean people during weight gain (e.g., the holidays).  After a 10% weight loss, 64% of the weight is fat mass in lean subjects while a whopping 84% is fat mass in obese subjects.  Thus, obese people lose more fat and less muscle than lean people during weight loss (e.g., New Year’s resolutions).

Here goes nothing:
Take a 100 kg (220 pounds) obese person who has 50 kg fat mass (50% body fat) and a 70 kg (154 pounds) lean person with 14 kg fat mass (20% body fat). After 10% weight loss, body weight declines by 10 kg in the obese subject and 7 kg in the lean subject.  83.6% of the weight lost (~8 kg) is fat mass in the obese subject and 63.7% (~4 kg) is fat mass in the lean subject:

After 10% weight regain, body weight increases 9 kg in the obese subject and 6 kg in the lean subject.  60% of the weight gained (5 kg) is fat mass in the obese subject and 80% (5 kg) is fat mass in the lean subject:

Rinse.  Repeat:


By the end of 3 complete yo-yo cycles, the obese person is down 3 kg body weight, but more importantly their fat mass has declined by 9 kg, from 50% to 42% of their body weight (winner!).  The unfortunate lean subject, however, despite being 2 kg lighter, now has an additional 2 kg of fat mass; in other words, they lost weight but got fattier (20% body fat to start out, 23% by the end).

To be clear, this study has never been done.  But Leibel, Rosenbaum, and Hirsch’s data are impeccable so any flaws in this hypothesis don’t stem from there.  The lean subjects in their study were 154 pounds; clearly not a population in dire need of weight loss.  Perhaps yo-yo dieting got a bad rap from skinny people trying to get skinner, who instead got fattier and told everyone else to give up if dieting didn’t work the first time.  I’m not against pharmacotherapy or bariatric surgery for those in whom diet has failed, but saying “I’m not against” it is a far cry from saying “I’m for it.”  Furthermore, given the results from this thought experiment, among other things, I’m definitely saying “try, try again.”

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Gluc-a-gone wild, Op. 60

optional pre-reading

Q. What happens to a type I diabetic when you 1) withhold insulin, 2) provide insulin, or 3) withhold insulin and suppress glucagon?  (Charlton and Nair, 1998 Diabetes)…

A. You learn glucagon is the bad guy.

Divide and conquer

Zero insulin makes you hyperglucagonemic, hyperglycemic, and ketoacidotic (see first column).  Insulin cures all of these things (second column), but they aren’t caused by insulin deficiency, per se… they’re caused by high glucagon, which itself is cured by insulin (second column) and SRIH (somatostatin, third column).  Cure the hyperglycemia by inhibiting glucagon and pathological diabetic ketoacidosis suddenly becomes physiological ketosis.

Uncontrolled diabetes also wastes muscle:Zero insulin makes you hypermetabolic and increases amino acid oxidation.  Insulin cures this, but again, it appears to be driven by hyperglucagonemia, not insulin deficiency.

Glucagon directly correlates with energy expenditure, and this isn’t the good metabolic rate boost sought by dieters, it’s the type that indiscriminately burns everything including muscle.  High protein diets also increase energy expenditure, but in pathological hyperglucagonemia, the amino acids come from muscle, not food.

The above mentioned study is most relevant to type I diabetes.  The following study is about glucagon and the far more common type II diabetes (Petersen and Sullivan, 2001 Diabetologia).

The effects of hyperglucagonemia can be blunted by glucagon receptor antagonists (GRAs).  In the figure below, a GRA (Bay-27-9955), was administered immediately prior to a glucagon infusion.  The GRA significantly reduced blood glucose levels, an effect largely attributed to the reduction in endogenous glucose production:One of the ways GRA’s accomplish this is by keeping glucose tied up in hepatic glycogen instead of flooding into the plasma (Qureshi et al., 2004 Diabetes; “CPD” is the GRA used in this study).  The figure on the left is primary human hepatocytes; on the left is in mice.Another way of looking at this is in mice chronically treated with glucagon or glucagon plus a GRA.  Glucose tolerance is obviously deteriorated by glucagon treatment, but is completely restored by a GRA (Li et al., 2008 Clinical Science):

One of the most severe side effects of diabetic hyperglycemia is nephropathy, which is similarly cured by GRA treatment:

The physiological role of glucagon is to prevent hypOglycemia; but hypERglycemia is the problem most of the time.  Don’t get me wrong, hypOglycemia can be deadly, but 1) it’s not nearly as prevalent as hypERglycemia, and 2) inhibiting glucagon doesn’t cause hypoglycemia, there are a battery of counterregulatory hormones that prevent hypoglycemia.

Furthermore, reducing glucagon action isn’t limited to glucagon receptor antagonists (GRAs), leptin and amylin can do it too!

And while gastric bypass surgery is easily more extreme than GRA’s and leptin or amylin therapy, it’s magical effect on diabetes remission might also be partly attributed to glucagon suppression (Umeda et al., 2011 Obesity Surgery):

Convinced yet?


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Hedonism, take II


More on the relationship between obesity, delicious food, and the magic of gastric bypass.

Roux-en-Y gastric bypass surgery changes food reward in rats (Shin et al., 2011 Intl Journal of Obesity)

I wish I knew how, but this study definitely shares a theme with the remarkable effects of a bland diet and spontaneously reduced caloric intake in obese but not lean subjects, (from the first post in this series, found here).

In brief, there were 3 groups of rats in this study: 1) diet-induced obese (“sham”); 2) diet-induced obese rats that underwent gastric bypass surgery (“RYGB”); 3) chow-fed lean controls (“lean”).  The dietary regimen was a kerfuffle, but that wasn’t really the point of the study; to make the rats obese, they were given standard chow, a purified high sugar high fat diet, and chocolate-flavoured Ensure all at once…  and we have no idea how much of each they were consuming :/    But here’s the nutrient breakdown of each anyway, by calories: 

and here is a rough ingredient list:

HFD, high fat high sugar diet

They performed a battery of psychological evaluations designed to empirically measure how much an animal “wants” or “likes” a rewarding food.  Call me simple, but I would’ve rather just seen how much of each of the above diets the rats consumed when presented with all 3 simultaneously.  If most of their calories came from the sweet chocolate-flavored Ensure, then I’d say they still liked rewarding foods.  If on the other hand they selected more of the sugar-free chow, then they probably don’t care as much for rewarding food.  Maybe this wouldn’t fly in psychonutrition circles, but I don’t really think such circles exist.  Alternatively, would RYGB rats have lost more weight if they were fed exclusively chow compared to those given Ensure?  Fortunately, this question was addressed in an earlier manuscript by Zheng (Meal patterns, satiety, and food choice in a rat model of Roux-en-Y gastric bypass surgery [Zheng, Berthoud, et al., 2009 AJP])

When given the sugar-free chow diet, the control rats eat less.  When given a high sugar high fat diet, the control rats eat more.  RYGB rats don’t seem to care.  But that’s kind of exactly what Shin showed by complicated psychological tests:

Lean and sham (obese) rats like a very sweet beverage (1.0 M sucrose) significantly more than a more bland solution (0.01 M sucrose).  RYGB rats don’t seem to care.  This was repeated to a tee in another group of “obesity-prone” rats suggesting it might be a true product of the gastric bypass surgery:

And oddly enough, human subjects that have undergone roux-en-Y gastric bypass surgery seem to be able to detect much lower concentrations of sucrose but not like it as much (they can “taste” it more, but might not “like” it more)  (they are satisfied with less-sweet foods) (Changes in patients’ taste acuity after Roux-en-Y gastric bypass for clinically severe obesity [Burge et al., 1995 JADA])



Are these findings related to obese humans who spontaneously consume significantly less of a bland diet?  (recall obese but not lean human subjects lost weight on the bland diet).  Similarly, rats consume significantly more of a tasty junk-food cafeteria diet.  There is definitely something magical about roux-en-Y gastric bypass surgery; it is the single most effective treatment [cure] for obesity.  Obese humans eat less of a bland diet, roux-en-Y gastric bypass surgery decreases the “liking” of a sugar-rich beverage (but enhances one’s ability to detect sucrose)… RYGB and that bland diet caused massive weight loss in their respective [obese] subjects…   These things just have to be related, my spidey-sense is going wild


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