Physiological insulin resistance: The wild type mice

I've just got an afternoon to blog so I thought I'd put up something new before the daunting task of going through comments which have built up with the surf/work/weekend session that has (very pleasantly) limited net time.

I wanted to go through the data from the mice in this paper.

It's a Nature paper so I'm not sure how I got the full text, but there it is on the hard drive! The brown fat ablated mice are interesting enough for a post in their own right eventually, so it's the control groups that I'm looking at today. Ortmann does discuss the macronutrient preferences of mice, strain being one factor, and she does discuss in particular the role of early exposure to grains in future food choices, no surprises in what happens there! But any sensible mouse which has not been permanently broken by early exposure to lab chow loves fat. How much fat? Well, you have to let the mice choose for themselves. No lab chow for these mice. They got three separate food blocks, one lard/coconut oil, one casein and one of that sucrose/cornstarch poison so beloved of rodent researchers. Here's the composition of the blocks:





What did the mice choose? Here's the cumulative food intake from 4 weeks to 17 weeks of age. Look at the column WT (ignore the UCP-DTA column for today), these are wild type (WT) mice without any genetic engineering. They're lab mice.





Okay.... casein. It seems mice eat enough protein to grow, about 12% of their calories. How about that scrummie sugared cornstarch? I was thinking they might not have touched this junk with a barge pole, but those clever mice ate just under 6% of their calories from sucrose/starch. Very close to what I eat! And the rest? FAT!

These macronutrient ratios are pretty close to those of the Optimal Diet. It is a genuine high fat diet. There is nothing Western or Cafeteria about it. It's JK all the way.

The lab chow is unspecified but was probably Purina 5008, low fat, high starch, minimal sucrose. A bit Ornish like...

So what happened to the mice?







As you can see the free choice mice (WT 3CD, black triangles) grew indistinguishably from mice on lab chow (WT SD, black circles) re bodyweight.

Now look at energy intake, again it's only the WT SD black circles of the lab chow normal mice we are comparing to the WT 3CD black triangles of the normal type mice eating to the Optimal Diet (by choice).






Would you rather eat 90kj/d or 70kj/d to maintain your growth rate under unlimited food conditions?

Finally it's pretty obvious that eating all that saturated fat will make you instantly insulin resistant and diabetic. Well, interestingly, the fasting glucose is actually higher in the high fat eating mice.



The hatched bar is the high fat eating mice, again its the WT groups we're looking at.

Aha, the AHA was right all along. No! Insulin sensitivity is the same in high fat or lab chow mice. Each mouse was injected with insulin and their fall in blood glucose in response to this tracked. The bigger the fall, the more sensitive you are to insulin. Don't play this at home, an OGTT is much safer!







Again it's the black triangles eating to the OD. Although there is no statistical testing of the difference from the black circle lab chowers, the glucose fall in response to exogenous insulin is GREATER in the high fat group and eyeballing the Standard Error bars suggests that the difference is probably significant.

So does a high fat diet cause insulin resistance? Only in so far as there is a higher fasting glucose level in this group, of which I'm an honorary member. In terms of shifting glucose when I need to, it's effortless. But if I'm shifting free fatty acids because I'm exercising without having eaten I can still use NEFA to fuel muscle, have that muscle reject glucose and so leave that glucose for my brain, if I'm using it at the time that is...

Peter