Saturday, 2 June 2012

Of mice and men, Kleiber's Law & FIRKO.

More musings from my fevered brain!

I remembered a discussion on Hyperlipid about FIRKO mice.

Note: FIRKO stands for Fat Insulin Receptor Knock Out and it results in White Adipose Tissue (WAT) having vastly reduced uptake of nutrients, thus inhibiting gain of WAT. Brown Adipose Tissue (BAT) has up-regulated uncoupling proteins i.e. BAT produces more heat. See also Research data concerning maximum life span.

What was also interesting was that, in a study where mice's VMH (VentroMedial Hypothalamus) was also deliberately damaged, mice ate more food but didn't gain any weight. What? The Energy Balance Equation doesn't apply?

Mice weigh very little (~30g), so they can't burn off significant amounts of energy through exercise the way that humans can. So, how on Earth can mice eat more without gaining any weight?

Peter Dobromylskyj gave me the answer. As a veterinary surgeon, he works on rodents, so he knows about this. Rodents under anaesthesia easily get hypothermia. The penny dropped! Mice have a very high surface area to mass ratio (see the above graph) compared to adult humans. As heat is lost through the skin, small animals like mice are at a disadvantage when it comes to heat conservation. They have behaviours for conserving heat e.g. covering themselves in bedding (which reduces heat loss) or huddling together in groups (which reduces overall surface area to mass ratio). Anaesthesia prevents these behaviours.

Any excess energy intake that cannot be stored due to FIRKOisation is disposed of by increased heat production in BAT and increased heat loss by reduced heat conservation behaviours. Simples!

Most adult humans have very little BAT, so they are unable to perform the same trick. If a human raises their metabolic rate significantly (say, by taking 2,4-Dinitrophenol), they tend to overheat & die.

You could try sitting in a bath of cold water. ;-p That would make me really cold and hungry (and wet!), so I would eat ravenously afterwards. But that's me. Your Mileage May Vary.


LeonRover said...

Well, quite.

I preferred "Cannery Row" to the following tune:

Have you read "The Short Reign of Pippin IV" ?

Nigel Kinbrum said...

I'm out for the night!

LeonRover said...

I agree: You're outa' sight (& outa' mind).

LeonRover said...


john said...

So what do you propose would happen to a larger animal like a FIRKO human?

Nigel Kinbrum said...

john said...
"So what do you propose would happen to a larger animal like a FIRKO human?"
The same thing that currently happens to FIR humans i.e. type 2 diabetes. Excess nutrients have nowhere to go (if muscles aren't using them due to sedentariness), so they stay in circulation.