Surwit diet and derivatives (5) People and mice

George Henderson put up this link in comments to the last Surwit post

Small Amounts of Dietary Medium-Chain Fatty Acids Protect Against Insulin Resistance During Caloric Excess in Humans

It's a beauty. Following a standardised three day over feeding regimen, roughly one and three quarter times normal calorie intake, 82% of total calories as fat, you develop insulin resistance. Well, you do if the fat is predominantly saturated fat.

No one should be surprised at this. Sustained deliberate massive overfeeding has nothing to do with developing obesity in real life. Saturated fat makes adipocytes unwilling to accept this excess dietary fat so it is deposited anywhere the body can put it. The normal response to eating nearly twice your normal calories in a day is to eat less next day. But not if you are in an overfeeding study. So the unwillingness to store calories continues and the body's attempt to resist this (insulin resistance) continues.

If you do the same but replace just 30g of the 450g of saturated fat with MCTs (about 5% of total energy) you don't develop insulin resistance.

This is considered to be a Good Thing.

Personally, I think it's not. If you add some MCT oil to your saturated fat it is very clear that there is no resistance to the excess calories being put neatly and tidily in to storage. In to adipocytes. Which will expand. Which we call obesity. As in the obesogenic Surwit rodent diet...

The prediction from the Protons/ROS hypothesis is that under the Surwit diet that insulin sensitivity should be "improved" in the early stages due to the MCT lipids. That might actually show best if rodents were fed the Surwit diet but restricted in calories so the late onset obesity related insulin resistance doesn't obscure the underlying pathology.

I wonder, that's not difficult and might have been done... Time to hunt.



This was the first hit:

Fat, carbohydrate, and calories in the development of diabetes and obesity in the C57BL/6J mouse

by the original Surwits. Sadly Mr and Mrs Surwit didn't specify which high fat diet they used in this study. They cite two refs, one used coconut oil 

Differential effects of fat and sucrose on the development of obesity and diabetes in C57BL/6J and A/J mice

and one used "1850" by Bio-Serve.

Diet-Induced Type II Diabetes in C57BL/6J Mice

Modern Bio-Serve F1850 is a lard based high fat diet, so we'll never quite know which diet we are talking about in the restricted feeding regimen. However the question is the same: Do "high fat" diets work by sensitising adipocytes to over respond to insulin? Be that linoleic acid from lard or medium chain fatty acids from coconut oil.

This should show if you feed the obesogenic diet but restrict calories. Which is exactly what the Surwits did.

The high fat/restricted calories mice were not fed to be weight matched with the low fat mice, merely to be calorie matched. Of course, despite "calories in" being matched, the pair-fed high fat diet mice gained more weight than the low fat mice. I'm guessing they were a) very hungry and b) hypometabolic.

Here are the weights:

Blood glucose and insulin were measured at the times marked by the arrows. Glucose looks like this:

which is pretty boring and appears to reflect the relative body weights. Insulin comes out like this:

If we stick the hungry fat mouse values through an HOMA IR calculator (which gives silly numbers but allows a comparison) we get an HOMA score of 13.9 while for the control mice we get 16.2. The high fat fed partially starved mice are more insulin sensitive than the control mice. Given access to more food this insulin sensitivity would undoubtedly make them become fatter. And the fatness would eventually render them insulin resistant per se.

TLDR: The mice which are on a high fat diet but underfed are fatter than controls (despite equal calories) but have LOWER insulin and lower insulin resistance than controls. Surwit diets make you insulin sensitive and this makes you fat.

With thanks to George and the Surwits.

Peter