Well now I think I can. The insight needed comes from a non related paper on the effect of knocking out the sweet taste receptor in mice.
So, let's have a look at the RQ data from the CLAMS apparatus in this paper:
Disruption of the sugar-sensing receptor T1R2 attenuates metabolic derangements associated with diet-induced obesity
And in particular from this next set of graphs. They are interesting because they cover two complete days in the CLAMS equipment.
Look at the grey and the black lines first, these are control and sweet receptor KO mice, being fed pretty standard low fat crapinabag. We can see that between day one dark period and day two dark period in the CLAMS equipment that a) the peak height of the RQ rises, b) carbohydrate oxidation rises and c) lipid oxidation falls. No one did stats to compare these two days with each other so I don't know what the p value might be, but the trend certainly looks very real to me. No one altered the food macros between day one and day two.
I think mice, like humans, cut their calories when you put them in to a respiratory chamber or in to a CLAMS apparatus. Certainly for the first two or three days of mice in CLAMS.
In this T1R2 KO study you can see evidence for the the improving intake of (carbohydrate based) food between day one and day two which is inseparably linked to the rising RQ. There had been a day of acclimatisation before the two study days which will have minimised this trend but it's very much still visible. The change is less obvious (but still present) for the fat fed mice (red coloured traces) but it's not so clear cut in these mice because they are largely either oxidising fat from their diet or fat from their adipocytes, both of which look pretty much the same from the RQ point of view.
Core insight. You can alter RQ away from the macros of a (high carbohydrate) diet by simply eating less. Adipocyte fat makes up the difference in calories and this automatically drops the RQ. Let's take this idea and look at the RQ figure from Kahn's paper.
In a normal mouse, on normal low fat chow, the RQ during the early feeding period rises to above 1.0 due to de novo lipogenesis combined with fat repletion/storage. Kahn's control mice (SHAM) started with a RQ at around 0.88 and they slept through the light period so dropped their RQ to around 0.75. When they started to feed with the arrival of the dark period (on their high carbohydrate chow) in the CLAMS apparatus the RQ only rises to 0.88. In real mice eating this sort of chow the RQ should rise to 1.2 for a few hours.
The RQ will not rise to 1.0 if the mice fail to eat enough carbohydrate to meet or exceed their energy needs. If they don't eat enough they will continue to utilise body fat and this will lower their RQ below that of a mouse eating to weight stability. These mice did not eat enough carbohydrate to suppress fat oxidation. The RQ says so. The absolute food intakes are below but these are fairly irrelevant compared to the RQ data.
They were put in to the CLAMS apparatus with no suggestion (in the methods) of an acclimatisation period. I think the mice were frightened and dropped their food intake. We can see from the RQ of both groups that at no point does this even approach, let alone exceed, 1.0 (in the acclimatised mice in the T1R2 KO paper figure the RQ reaches 1.1 at the peak of feeding on day 2, ie CLAMS day 3).
Summary: Both of Kahn's groups are oxidising fat to give a low RQ on an high carbohydrate diet and the only way they can be doing this is if the fat is coming from their adipocytes. They are not eating enough of their carbohydrate based diet to maintain fat storage or to raise the RQ.
That just leaves us to ask why the control group are oxidising more fat than the intervention group. Is this a magical preference of the intervention group to oxidise glucose? Is that why they are so slim? I know that sounds strange but that's the conclusion in the paper. Logically, oxidising FAT makes you slim. Storing fat makes you fat. But that's under ad-lib conditions. At the time of the hypocaloric 24 hours for Kahn's mice in the CLAMS apparatus we have these data available from which we can estimate fat stores at a given time, week ten in particular:
The white diamonds are still the controls/sham operated. They carry about 10g of fat at week ten. The black squares are the intervention group, they carry about 5g of body fat at this time. If both groups cut calories acutely during their day of anorexia in the CLAMS apparatus, I would expect the animals with the most adipose tissue to release the most FFAs. And oxidise the most FFAs. That has to be the control group, because they're a lot fatter to start with. The intervention group has less stored fat available, so oxidises less fat. Interestingly the fatter control group ate 3.9g of carbohydrate based food in the CLAMS vs 4.2g for the slimmer intervention group (ns), which just might reflect less hunger in the fatter control mice because they are accessing their bigger fat stores, ie the control mice appear to run on fat (because they are doing so on this one single day). A lack of stored fat in the intervention group is why they ate more (carbohydrate based) food and utilised less adipose derived fat. So this group appears to run on carbs, judging by their RQ. But the RQ over the rest of their lives, in either group, while eating normally, to satiety, outside the CLAMS apparatus, is a mystery.
But yay! The CLAMS equipment is almost certainly working correctly. The RQ graph is very explicable. It probably tells us NOTHING about the substrate oxidation under non-CLAMS conditions, but we can speculate about that in another post.
Trying to make inferences about overall post-intervention metabolism, based on a single day in a very novel (and possibly frightening) environment under acute hypocaloric conditions will set you up for a hiding to nothing as far as comprehension and understanding of your intervention are concerned. But given enough thought the results at least become comprehensible.
Now I'm happy.
Peter
Now that I'm happy I might have a think about why the slim, subcutaneous to visceral fat-transplanted mice in Kahn's study might have come to remain slim. Clearly, from the fat mass graph, the transplantation of subcutaneous fat in to the location of visceral fat does do something...
