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 heat.

Of great interest was that, in a study where a FIRKO mouse's VMH (VentroMedial Hypothalamus) was deliberately damaged, the mouse ate more food but didn't gain weight. This appears to defy Energy Balance theory.

Mice weigh ~30g, so they can't burn much energy through physical activity. How can mice eat more food but not gain 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. Mice have a 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 heat conservation 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.

Most adult humans have a tiny amount of BAT, so they can't do this. If an adult human raises their metabolic rate significantly (say, by taking 2,4-Dinitrophenol), they tend to die from hyperthermia.

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.

See also It’s the Calories, Stupid.


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.