Category Archives: Energy balance

diabulemia

This isn’t a “magic bullet,” it’s a buckshot aimed at a barn door.

Yes, I think sugar and empty calories, and the associated hyperinsulinemia are the bane of anyone with obesity or any sort of hyperplastic fat tissue disorder.  And yes, this is the worst type of evidence to support such a stance, but when you’ve got lemons, well…

Make no mistake, diabulemia may as well be spelled DIE-abulemia.  It’s not a laughing matter.  But yeah, well, lemonade, etc.  So here it goes

Diabulemia

Type I diabetics have low insulin and are lean; type II diabetics have high insulin and are not.  Insulin injections in either population promotes hyperplastic fat growth.  Sounds scary, right?  It is:

insulin

This poor soul unfortunately restricted his insulin injections to only two sites.  Make all the jokes you want, but the effect is obvious…  this is happening everywhere in hyperinsulinemic heavyweights (not just two specific sites).

CHO III Picture 279

 So what do Type I’s do when they want to lose some fat mass?  Stop jabbing themselves with insulin. Unfortunately, it’s really that simple.  Type II’s and anyone with excess or hyperplastic fat tissue can do the same with low carb or keto, although this would be a great benefit to their overall health.  But for Type I’s… not so much – they need insulin to prevent the horrific manifestations of ketoacidosis, which includes but is not limited to: death.

Type I’s are hyperglycemic because of low insulin; insulin therapy prevents diabetic ketoacidosis, a deadly condition.  But for those who simply choose to selectively reduce their insulin dosage, they: 1) don’t die; 2) lose fat; and 3) get hyperglycemic and incur all the damage that ensues (retinopathy, nephropathy, neuropathy).  Furthermore, they’re walking on thin ice – DKA is lurking.  It is just as stupid yet more dangerous than using tapeworms to lose weight.

tape-worms

Type II’s are hyperglycemic because of insulin resistance; a condition that is pathologically neutered via carbohydrate restriction.  Type I’s who reduce insulin injections to decrease fat mass are doing just as much damage as Type II’s who DON’T reduce carbohydrate intake.


Diabulemia is akin to an eating disorder.  Biologically, the lack of insulin allows fat to be released from adipose tissue with gravitas, and it prevents glucose from being stored in any meaningful capacity.  You’re literally pissing calories here, burning ’em like crazy there; all of which is a helluva lot easier than “eating less moving more” … which is why diabulemics do it (because they have the option [unlike the rest of us]).  Diabulemia is good from a fat loss perspective, but will most definitely contribute to severe and possibly deadly complications down the line.   Carbohydrate restriction, however, is a win-win-win… (for everyone except The Man, so perhaps it’s a win-win-win… fail)

This isn’t a “magic bullet,” it’s a buckshot aimed at a barn door.


Humans aren’t big rats, but here it is again, anyway:

Leptin deficiency causes insulin resistance induced by uncontrolled diabetes (German et al., 2010)

I’m ignoring the brunt of this paper and only focusing on the positive control groups.  [Positive controls… meaning they were included because they would definitely exhibit the expected response.]

Force rats into a state of diabulemia, and their insulin levels plummet, blood glucose soars, and they become ravenously hungry (open squares in the graphs below).German I

But lo and behold, fat mass atrophy ->German II

Eat less move more?  Well, they certainly didn’t “eat less…” (see above) … and:German III

nor were they “moving more.”  Low insulin seems to have a way to bypass that whole “eat less move more” thing (eg, Metabolic rate per se).

 

Throwing the baby out with the bathwater works if the baby is fat and the bathwater is insulin.  (no, not a fat baby.)

 

calories proper

 

 

40 years ago a group of researchers turned ketosis into poetry.

But first, a brief primer.  In red.

“The glucose muscle-sparing effect of fat-derived fuels” 

or, the Randle Cycle 2.0.  it’s like a course in life enhancement.

Part I.  Intermediary metabolism

The glucose-fatty acid cycle
The Randle Cycle, as originally proposed, states that fatty acid oxidation inhibits glucose oxidation.  This is good because during starvation, every tissue than can survive on fatty acids instead of glucose should do so, sparing as much precious glucose as possible for the brain.

The glucose-sparing effect of fat-derived fuels
A critical vital horcrux to this is in the oh-so-humbly-disguised phrase “fat-derived fuels.”  The fat-derived fuels are ketones, and they are rescuing the brain from starvation (ie, neuroglycopenia); they do so by supplementing glucose as a fuel source.  Ketones are good at this; many tissues are happy to oxidize ketones when they are available.

The glucose muscle-sparing effect of fat-derived fuels
Ketones are derived from fat.  During prolonged starvation, glucose comes from skeletal muscle amino acids (eg, alanine).  Ketones spare glucose.  Thus, ketones spare muscle.  QED.

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obesity sans overeating :(

As stated in the Laws of Energy Balance, you can get fat without eating more, and unfortunately there are about a thousand different ways to do so.  Here is yet another:

Long-term, intermittent, insulin-induced hypoglycemia produces marked obesity without hyperphagia or insulin resistance: a model for weight gain with intensive insulin therapy (McNay et al., 2012)

While it has a lot in common with fat gain diet-induced insulinemia and diabetic insulin therapy, this isn’t the greatest “model for weight gain with intensive insulin therapy.”  But it’s an interesting one nonetheless.

chocolate peppermint doughnuts

In this model, normal rats are fed the standard fare, but once weekly get jabbed  with 10 U/kg insulin; enough to drop glucose to ~35 mg/dL (seriously hypoglycemic).  Yes, this is an insulin spike, but not like the ones we normally see – usually, carbs cause the insulin spike but also provide the glucose necessary to prevent hypoglycemia.  These rats weren’t so lucky.

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Biohacking holiday weight gain

What should you eat before the big feast?  (hint: eggs.)  And don’t try to compensate in advance by eating less, this will only make you hungrier.  Furthermore, foods in your regular diet are probably healthier than holiday fare, so you definitely don’t want to eat fewer healthy foods to make room for empty calories.

Tip 1. 

Variation in the effects of three different breakfast meals on subjective satiety and subsequent intake of energy at lunch and evening meal (Fallaize et al., 2012)

Participants were served only one of these for breakfast:

And given unlimited amounts of these for lunch and dinner:

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Philosophy of the faux-low carb mouse and others like it

The Laws of Energy Balance are always maintained.  Here are some insights into how this is accomplished from a mouse perspective.  A hormonal milieu which is unfriendly for fat storage will make you lean, but not by magic.  We’ve got: 1) reduced food intake; and/or 2) increased energy expenditure.

Recall the faux-low carb mouse (Ins1+/-; Ins2-/- aka InsKO; Mehran et al., 2012).  They can’t get fat because of an inability to develop hyperinsulinemia.  Food intake isn’t reduced, so energy expenditure goes up.  Since the fat isn’t stored, it needs an “out,” so it either inhibits food intake or ramps up energy expenditure; InsKO gives us the latter.

While not hormonally-mediated, PPARg+/- mice can’t get fat because of defective adipogenesis and they handle this problem both ways; by reducing food intake and increasing energy expenditure (Kubota et al., 1999).  Similar to InsKO, PPARg+/- have lower insulin, but the primary defect in these mice is defective adipogenesis.  They can’t store fat, so this unstored fat: 1) tells the brain there’s plenty of fuel around so stop eating; and 2) ramps up energy expenditure to burn itself off:

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The faux-low carb mouse and a diatribe

The faux-low carb mouse

Hyperinsulinemia drives diet-induced obesity blah blah blah (Mehran et al., 2012)

The researchers generated a mouse with half as much insulin as normal mice.  Physiological insulin levels remain intact, but hyperinsulinemia is genetically inhibited.  For the sake of simplicity, we’ll call them “InsKO.”

When fed a high fat diet, normal mice become markedly hyperinsulinemic (pink line) whereas InsKO mice maintain relatively normal insulin levels (red line).  Blue lines are chow-fed mice; similar trend but less interesting.

divide and conquer

InsKO mice don’t get fat,

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Sir Philip Randle and the effects of blocking fat oxidation

The Randle Cycle, put forth in 1963, dictates that increased fatty acid oxidation inhibits glucose uptake and increased glucose oxidation inhibits fatty acid oxidation – it just makes sense.  Insulin enhances glucose uptake and oxidation while suppressing lipolysis; growth hormone, cortisol, and adrenaline enhance lipolysis and fatty acid oxidation which suppresses glucose oxidation.  Low carbohydrate diets reduce insulin, and the reduced glucose oxidation is metabolically irrelevant because of reduced glucose intake (by definition).  This is critical information.  And as a student of basic intermediary metabolism, I prefer the Randle Cycle over any number of alphabet soup recipes to explain metabolic phenotypes (eg, fat and carbs as opposed to IRS, Akt, Jnk, ERK, etc., etc.).  Many valuable lessons can be learned from understanding permutations of the Randle Cycle.

For example,

Inhibition of carnitine palmitoyltransferase-1 activity alleviates insulin resistance in diet-induced obese mice (Keung et al., 2012)

divide and conquer

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NRT = nicotine replacement therapy

NRT improves quitting success rates and reduces cessation-induced weight gain.  It’s a fact; and there are a lot of anti-addictive pharmacological interventions that do too.

Dear obesity researchers, primary care physicians, and smokers,
Pay attention.
Sincerely,
Bill

Rimonabant is the anti-“munchies” drug that blocks the marijuana receptor CB1.  It causes weight loss.  But 20 mg daily also increases the odds of successfully quitting smoking by 50 – 60% (Cahill and Ussher, 2007).

Relevance?
Marijuana: not really addictive.
Obesity diets: delicious, but not really addictive.
Cigarettes: definitely addictive.
Rimonabant: anti-addictive.  It causes weight loss in overweight but not lean people, perhaps because lean people don’t eat obesity diets (?).

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The curious effects of calories in mice

What is the biological impact of a history of obesity and weight loss?  The metabolic trajectory of two calorically restricted skinny mice depends entirely upon whether or not they used to be fat.  The end of this story might be: ‘Tis better to have lost and re-gained than never to have lost at all; or it’s just an interesting new take on the body weight set point theory.

Caloric restriction chronically impairs metabolic programming in mice (Kirchner et al., 2012)

divide and conquer

Part 1.
Study 1. Calorie restricted lean mice: the effect of diet composition.

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Coffee and cigars, the breakfast of champions

Or more specifically, caffeine and nicotine… or really just nicotine.  Today is about the lesser of two evils: nicotine, Mother Nature’s little helper (the other evil being cigarettes [not coffee]).  This curious little molecule is an anti-inflammatory memory boosting appetite suppressant.  If it didn’t screw with the reward mechanisms in your brain, it’d be a vitamin. Part 1.  Cigarettes, nicotine, and metabolic function Exhibit A: Activation of the cholinergic anti-inflammatory pathway ameliorates obesity-induced inflammation and insulin resistance  (Wang et al., 2011) translation: “nicotine is good for mice.” Continue reading