Fat Metabolism in Formerly Obese Women: Part II Resting Substrate Usage

Continuing the discussion from Part I

Fat metabolism in formerly obese women
Ranneries, et.al.  AJP-Endo, 1998.

In this part I wish to address the respiratory quotient, RQ.  The RQ is a measure of the relative amounts of energy derived from glucose oxidation vs. fatty acid oxidation.  

To recap the subjects of this study, when obese, the FO (formerly obese) subjects had body weights in excess of 120% normal weight.  They followed a conventional CRD to lose the weight and were weight stable for at least 2 months at 110% normal weight.  So weight losses were in excess of 10% bw and ranged from 15-20kg (33-44 lbs).    The FO & C groups were well matched as seen in Table 1.

So the subjects were fasted overnight, and had not engaged in strenuous activity for three days prior to the study.  They "sat quietly" for 15 minutes prior to the baseline measurement which is all I'm going to discuss here.  The results "cropped" for just the resting substrate use are shown in the table at right {as always, click to enlarge}.  Now this is quite dramatic!  As a percentage, controls utilized less than 10% carbs and almost 80% from fat, while the formerly obese utilized almost 50% from carbs and only about 35% from fat.  This is a rather startling difference.  

The resting RQ was significantly higher in FO (0.849 ± 0.07) vs. the controls (0.742 ± 0.015).   The authors point out that the elevated NEFA (988 vs. 704 μM) and lower insulin levels (34.4 vs. 69.0 pM) in the FO might indicate a persisting negative energy balance, but note that underfeeding generally reduces RQ which was the opposite of what was observed.  

Thus the authors conclude:
Despite higher circulating levels of NEFA, the FO had lower fat oxidation during rest ... and the difference in fat oxidation was more pronounced when we adjusted for differences in plasma NEFA concentrations. Therefore, the study suggests that the major cause of the lower fat oxidation in FO may be an impaired skeletal muscle uptake and/or oxidation of fatty acids.
I'm going to discuss the exercise portion of this separately in Part III, but it bears pointing out that there were no differences in substrate usage during exercise.  However, these subjects apparently had no impaired fatty acid uptake or oxidation in the exercised state -- when required rates to sustain activity were much higher.  So  why would the impairment manifest itself only at rest?  Still, if there's something to the FO burning more carbs at rest, and they appear to be more insulin sensitive (as demonstrated by reduced insulin levels), I don't get the logic of eating a VLC/HF diet as some means to "repair" things.  Fire up the engines and the substrate utilization differences disappeared.

I found another paper looking at the formerly obese.  This time from the National Weight Control Registry.  Here, the 40 FO's (including 7 men) had maintained at least the minimum weight loss to qualify (30 lbs) for one year, and the average maintenance was almost 10 years.  What they found is shown in the table at right.  No significant differences!

Whatever effect Ranneries et.al. saw after 2 months seems to have almost entirely disappeared by 1 year and beyond.   So ... do the obese have broken metabolisms that are retained even with weight loss??

There's one other thing that bothers me about this whole notion of mitochondrial function.  The only difference between energy derived from glucose and fatty acids as far as the mitochondria are concerned is that most of glycolysis occurs outside the mitochondria.  Pyruvate dehydrogenase is associated with the mitochondria and converts the pyruvate into acetyl CoA.  The very same acetyl CoA that is produced by the oxidation of fatty acids within the mitochondria.  Your mitochondria don't really function any differently from this point on -- acetyl CoA feeds into the Krebs cycle and the reducing equivalents feed into the very same electron transport chain (ETC).  Many of the mitochondrial dysfunction studies I've seen deal with the ETC so something just doesn't quite sit right when I see these associated with lipid oxidation alone.  Just thinking out loud ...

In Part III I'll address the exercise portion of the Ranneries study.


You wrote:

"Whatever effect Ranneries et.al. saw after 2 months seems to have almost entirely disappeared by 1 year and beyond. So ... do the obese have broken metabolisms that are retained even with weight loss??"

Is it retained with weight loss ... or retained for some period afterwards? I.e., what is the implication of it disappearing by 1 year?

Is that the period just after weight loss is the most difficult? Or that some people are somehow able to retore their at rest FO capabilities while others aren't?

Interesting stuff!
psychic24 said…
Disagree with this study completely-- where are the controls that were at normal weight and then lost weight used as controls? To me this says nothing about formerly obese, rather about individuals who have lost significant weight compared to those who haven't (irregardless of their starting weight).
CarbSane said…
Hi Beth, I just think that 2 months is not enough to class someone as "formerly obese". The insulin levels at half those of weight matched seem awfully odd to me. OTOH, the NWCR data is rather spread out. You've got 30 lbs as the minimum to qualify (which is about what I lost in HS to go get to 110 and even flirt with 105 at times ... so I was hardly obese or formerly at that time!) and the maintenance ranged from 1 year to 43 years! Still, I've looked at their numbers and probably we're talking a median in the 3 yr range (with that 43 year skewing the average).

I guess to me it means some recover, others may not. The only real way to know if you're stuck or struggling is to get tested. It's too bad at least the RMR 10 minute CO2 test isn't more readily available.
CarbSane said…
psychic: In both studies the controls were weight matched never obese.
psychic24 said…
But these never obese folks didn't lose any weight, which is my point; one group had their metabolism altered by losing weight While the others didn't. U surmise that it's their previous obese state that causes the effect meanwhile I think it's the fact that weight( regArdless of whether it is excess or not) was shed that caused the effect. So the normal weight people need to shed weight in order to accurately use them as controls. Thought I was pretty clear about that in my previous post...
Duffy Pratt said…
psychic24 has a point but I would put it differently. To get the most out of a study like this, it should look at four groups at a minimum. Obese people who lost weight. Normal people who were weight stable. Obese people who remained weight stable. And Normal people who lost weight. Any of the last three groups could be viewed as a "control" for the first, and its not intuitively obvious to me which one actually should be the "control" group.

One other slight error in the post. You said the formerly obese went from 120% of normal weight to 110%. Whether it's a loss of 10% depends on how you measure it. I would have said that it was a loss of appox. 8.3%, using the 120% starting weight as the baseline.
perishedcore said…
Perhaps it has to do with the rate of adipocyte cell turnover. I can't find the reference, but I seem to recall that it's about 50% over two years. There might be a critical mass effect that requires the damaged mitochondrial containing adipocytes to turnover before the oxidative effects normalize.
CarbSane said…
Hi psychic, I didn't surmise that it was the obese state that "broke" the metabolism -- that's a topic for a different day. This study and some others I've seen are merely comparing the reduced to the never overweight. To compare, say, a 150 lb person who used to weight 200 lbs to one who is of relatively normal weight weighing 150 all along. Not to compare someone weighing 100 lbs after 50 lbs weight loss. Duffy, I do wish the first study had a longer time than 2 months, or had followed up after a year or more. The NWCR data seems to show that "recovery" of the metabolism -- whether it was caused by the obese state or prolonged energy deficit -- is possible.
CarbSane said…
@perished: Clearly, having been through it, our bodies continue to re-compose and change long after dramatic weight loss.
Sven Anders said…
Your body is constantly being renewed- after 90 days (up to 180 at the most), 98% of your body atoms have been replaced by atoms that you accumulate from your environment (mostly in
the form of food). I consider eating healthy, nourishing food as absolutely vital for anyone who has lost a lot of weight.