It’s the Calories, Stupid.

I thought I'd mark my return to blogging by taking the piss out of a certain Diet Doctor for his post It’s the Insulin, Stupid, who takes (and tweaks) Fig 7A from Hyperinsulinemia Drives Diet-Induced Obesity Independently of Brain Insulin Production.

At first glance, Fig 7A looks like a CIH believer's dream come true (apart from the words "High Fat Diet").

Hyperinsulinemia → Obesity.

Obesity is caused by too much insulin. Game, Set and Match to insulin.

Not so fast! Let's take a look at the rest of Fig 7.

Figure 7. Revisiting the Current Model of Obesity and Type 2 Diabetes(A) The most widely accepted model of the pathogenesis of obesity and type 2 diabetes posits that a high-fat diet leads to obesity and insulin resistance (there is debate about the relative order and causality of these). In this widely held view, insulin resistance then leads to hyperinsulinemia, which is followed by β cell exhaustion, and then type 2 diabetes. The accepted model is incompatible with our results that put the insulin hypersecretion genetically upstream of obesity.(B) Our data support a model whereby insulin levels must be kept low to maintain energy expenditure in white adipose tissue via the expression of Ucp1. Our data do not address the order of subsequent events after obesity (outside the yellow box), such as insulin resistance and/or type 2 diabetes, since they were not observed in our studies. In other words, the effects of insulin gene dosage on obesity are independent of sustained changes in glucose homeostasis or insulin resistance.

↑ Peripheral Hyperinsulinemia → ↓ Uncoupling Proteins (WAT) → ↓ Energy Expenditure → ↑ Obesity.

Obesity is caused by a reduction in energy expenditure. Game, Set and Match to The Energy Balance Equation. It’s the Calories, Stupid. In the mice in this study, energy expenditure is strongly influenced by insulin levels. In humans, not a lot. In humans, insulin can act as a stimulant and as a sedative.

I'm not an insulin denier as is obvious from my other blog posts. I'm still controlling my carbohydrate intake.
I'm not a food reward denier and I've been using food reward principles to lose some more weight.

The above post will probably annoy some people. Before wasting your time writing a comment, please note my Moderation Policy.

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.

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: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 surface area: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 behaviour. Simples!

Most adult humans have little BAT, so are unable to perform the same trick. 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.