Monday, November 5, 2012

Phat Fat Mitochondrial Energetics: Mobilization v. Accumulation

Adipose is Alive

In ancestral times, adipose stores may have determined longevity and survival past harsh cold winters. My ancestors moved from northern China 8-10+ generations ago to the mountainous areas of Taiwan (according to my dad several hundred years ago). I suppose those who didn't live past the impoverished seasons where food resources were scarce would not have made it, nor would their genes. I can thank them for my persistent fat stores *haa*. Adipose tissue is an endocrine gland which is know to secrete hormones such as leptin and adiponectin to control hunger, body energy balance and energy expenditure. These hormones are involved directly with mitochondrial biogenesis as well, in other words the production and destruction of the mini powerhouses found in all cells (except perhaps glycolytic-dependent cancer cells, which I think are all of them).

Whole body energy balance are determined by many factors, including most importantly:
1) demand
2) diet
3) d*ng hormones (or lack of)

All Organs Sync For Survival

Our brain coordinates many of the hormones that either mobilize or store adipose, e.g. fat. The brain includes the hypothalamus, pituitary, pineal, forebrain, hindbrain, midbrain and our senses for perception (ears, eyes, nose, taste, temperature, barometric pressure, etc). For example, insulin is triggered cephalically (via the brain): by tasting sweetness whether artificial or real, by smelling food, seeing food or even imagining food. Hearing? Hearing the neighborhood ice cream truck as a kid?

Humans Killed for Fat

Fat may have been the biggest boon for man during evolution (see prior animal pharm: humans as marine-based carnivores). Fat contained omega-3s concentrated up the food chain from green chlorophyll sources (grass, algae, etc) and into the muscle fat, organ meats, brains and fat stores of animals and seafood. The encephalization of ancient man is believed to be highly associated with the intake of dietary omega-3s. Perhaps the current de-encephalization over the last 100 yrs is related to the relative deficiency of dietary omega-3s? Or growing overabundance of omega-6s? THANK YOU VERY MUCH corn-fed cows and Keys.

Fat Yields the Most Energy in Human/Mammalian Energy Systems

Hormones for MOBILIZING fat stores far out number the hormones that ACCUMULATE fat. See diagram, modified from Gary Taubes GCBC from a 1965 table of hormonal regulation. Forgive me I use the term 'hormone' loosely because food is hormonal. Fatty acids bind PPAR receptors. We have ~ 3-4 routes to produce energy (some cells utilize glutamine, but I don't know which... neurons only?). Burning fatty acids yields the highest net energy unit (ATP). Why I've wondered? So many hormones promote the escape of fatty acids from temporary storage -- intramuscular, liver, visceral fat, brown fat and subcutaneous fat. Why do we readily release fatty acid energy? Sex, power, survival/suicide? Heat for 37C?

Taubes quoted Hans Krebs who received the Nobel in Medicine in 1953 'All three major constituents of food supply carbon atoms.. for combustion." GNG= gluconeogenesis (glucose/glycogen from any source -- protein, fat, carbs); ATP lesson (click HERE and UCD Lecture and med biochem):

Low Yield but Mandatory Without Oxygen
--anaerobic glycolytic (glucose/GNG) [Yield: 2 ATP]

High Yield in the Presence of Oxygen
--aerobic glycolytic (glucose/GNG) [Yield: 38 ATP] 
--aerobic beta-oxidation of fatty acids like palmitate [Yield: 129 ATP]
--aerobic beta-oxidation of fatty acids like stearate [Yield: 146 ATP]
--aerobic beta-oxidation of fatty acids like ketones [Yield: 51 ATP]
--aerobic oxidation of alcohol [Yield: 16 ATP]

Carbon lengths:
Glucose: 6-carbon carb
Palmitate: 16-carbon saturated fatty acid
Stearate: 18-carbon saturated fatty acid
Ketones (b-oh-butyrate, Ac-Acetate): 4 carbon fatty acid
Alcohol: 2-carbon 'the fourth food group' *haa* tequila is paleo, no?

Prior animal pharm: Palmitate Utilized Between Meals

Mitochondrial Medicine

Where does all this high energy production occur? Of course. Your mitochondria (the lower-net-energy anaerobic pathway is independent of mitochondria, occurs in the cytoplasma).

So. Don't scr*w up your mitochondria. That's like jacking your ride. Blowing out your carburetor.

...FLUNKING your human SMOG TEST.

Mitochondrial medicine is a new field but old premises still apply. The paleo evolutionary paradigm for which your mitochondria and DNA were perfected and honed over 2.5M years of natural and sexual selection are what we believe optimize health and maximize vitality.


Puddleg said...

Glycerol - there's another energy source, or is it counted as glucose?

Fructose is the preferred substrate for glycerol and this may be its biggest contribution towards triglyceride elevation; so those arguments about DNL might be a bit besides the point. Fructose and glucose in hepatocytes promoting the incorporation of dietary fats and ex-storage FFAs into triglycerides, (and being burned instead of the fats, which are exported) rather than a high rate of sugar turning to fat.

majkinetor said...

So, it turns down to mitos and its friends.

Perhaps it would be good to summarize such thing. What is mitos good for if they lack resources and boosters like:

- Vitamin A (missing hormone in your GCBC adapted table)
- Carntine and friends: Ascorbate, CPT...
- Complex N friends - Vit K2, COQ10
- Hormetic factors: Chromium, Metformin, Exercise
- Other: Carnitine, Vit B3....

Yeah, I would like to see some good mitochondrial resource.

Dr. B G said...

Yes glycerol (from TG backbones) will feed in...

I believe the liver is a short term depot for energy kinda like a mini freezer and the peripheral fat depots -- arms, backs, thighs, lower bellies -- the more deep long term storage units.... Thoughts? Liver fat is first to go, thighs and bellies, last. I've observed NASH reverse in only one month tracking elevated LFTs. Perhaps the role of fructose plays in.

Dr. B G said...

Maj ;)

So good to hear from you! Hope all is well! Yes all about the mitos!! Yes the Retinol was overlooked. I may need help on the mito resources... Pls feel free to hop in.


majkinetor said...

Hey, have a look at this one, if you didn't already:

Control of oxidative phosphorylation by vitamin A illuminates a fundamental role in mitochondrial energy homoeostasis

Would be nice to hear your thoughts on it. If true, for me it kinda proves that vegetarian diet is ill formed for humans.

Dr. B G said...

Hey Maj,

Absolutely concur -- vit A is critical for health, not just night vision and other superhero powers. I didn't know the oxphos mitochondrial connection! That's spectacular.

When the gut is dysfunctional and gut flora (the proper) absent, then vitamin A is not absorbed because it requires bacterial conjugation before the transporters can upload it.