In this study, 8 overweight/obese individuals (4M/4F, 30-60 y.o.a., BMI ≥ 27, otherwise healthy) were treated with a very low calorie diet (500 cal/day shakes + unlimited veggies) for 5 weeks followed by a weight stabilizing diet for 3 weeks. Abdominal subcutaneous fat biopsies were taken before and after the 8 week intervention.
There's a lot more here than what I'll address in this post. I hope to return to this at some future date, but in keeping with this series, I want to focus on the fat storage portions of the study. I have quite a bit in the pike regarding fatty acid transport and storage in various cell types. While fatty acids can be transported into (and out of) cells by passive means, it became apparent to me a while ago that the relatively rapid clearance of fatty acids into fat cells after a meal likely involved some active transport mechanism. As it turns out, uptake of fatty acids by adipocytes is facilitated by a fatty acid binding protein, FABP4. Triglycerides are stored in adipocytes (and other cells) in what are called lipid droplets, LD. Although the name implies something like a glob of fat, the lipid droplet is "coming of age" of sorts being recognized as a metabolically active organelle within the cell in much the same way as fat tissue has long since come to be recognized as so much more than just some passive depot for caloric excesses. This study looked at a protein known as vimentin which is possibly associated with lipid droplet formation/organization. More on this in a bit.
The table below summarizes the metabolic markers which were assessed in Week 6 immediately following the 5 week VLCD.
So the subjects lost an average of 9.5 kg or just over 20 lbs body weight, 7.1 kg (almost 16 lbs) of which was fat. Now I'm sure we'll get the usual "well, the diet was so low in calories it was effectively low carb" spiel as to why this diet worked, but such shake diets often do contain more carbs than some low carbers eat in a month. In any case, let's focus on that dastardly hormone insulin. Imposing a significant energy deficit on the adipocytes resulted in a more than 25% decrease in fasting insulin levels (the p-value of > 0.05 would not be statistically significant) and a 7% decrease in fasting blood glucose (the p-value of about 0.01 is statistically significant). Check out those NEFA/FFA!! Circulating free fatty acids were almost dropped in half!! You see, when the 8 subjects were weight stable at approximately 20 lbs heavier weights, their blood was swimming with free fatty acids -- you know, those NEFA the low carb shills claim are being locked away in your fat cells by your carb-induced insulin baths.
Here's what else they found:
... the uptake of fatty acids seems improved because on average there is a 40% increase in the abundance of FABP4 after the intervention. ... this provides evidence that weight reduction, in particular loss of fat mass, stimulates the basal function of triglyceride storage by adipocytes.
Note the adipocyte proteins were assessed after the full 8 weeks (3 weeks energy balance) so that the effect of an energy deficit was eliminated (or at least mitigated). From a formerly obese point of view, this is somewhat depressing news as always. At first glance, it seems that losing weight only primes the fat cells to gain it back. But let's pan back a bit and look at this whole picture of the purpose of our fat cells: to store energy for when we need it and keep excessive levels from circulation. So this is actually good news! Just 5 weeks and adipose tissue is dramatically transformed from overfilled and dysfunctional to doing it's thang protecting your non-adipose tissue from metabolic damage!
But here we see yet another contradiction in the woefully misguided TWICHOO. Yes, folks, what happens when you lower insulin, as was done in this study? The fat cells seem to have established a more fat-accumulation friendly environment upregulating FABP4. But something else also happens, what is described as "a reduced intracellular scaffolding of GLUT4" Hmmmm. So fewer glucose transporters but more fatty acid transporters. Remind me again what we store in our fat cells? Perhaps some comedians should stick to their day jobs rather than formulating garbage theories about how our fat mass expands to accomodate glucose. Sigh. But to sum up:
- Before: Higher insulin, higher GLUT4 scaffolding (to support glucose transport), lower FABP4 (to facilitate fatty acid uptake), elevated circulating NEFA.
- After: Lower insulin, lower GLUT4 scaffolding, higher FABP4, lower circulating NEFA.
Fat cells don't go wild accumulating fatty acids, rather they're fed up and just can't take it anymore! OK, sarcasm aside, this is yet another study that shows some rather dramatic changes in metabolic health with relatively minor changes in weight. I believe the findings here are important with respect to hormones and circulating metabolites. Although not statistically significant (probably due more to the small sample size and variation in levels than anything), the observed drop in fasting insulin levels of 25% is physiologically significant, and yet this was accompanied by an only 7% reduction in fasting glucose. What, yet again, seems to have changed the most? Those NEFA.
I'm going to save my analysis of Keith Frayn's latest review paper for the new year, but the findings here dovetail nicely with Frayn's more recent thinkings on fatty acids. Specifically, that adipocyte IR on the release side (inefficient suppression of HSL ) may be less important in the etiology of metabolic syndrome and diabetes, but rather that the defect occurs at the uptake side of the equation. This leads to inappropriately elevated basal circulating free fatty acids as well as inappropriately elevated postprandial NEFA with the composition of said fatty acids being potentially troublesome. Both lead to too much fatty acid storage in inappropriate places. Metabolically healthy lean individuals would have highly responsive fat tissue, presumably with sufficient FABP levels to whisk fat out of the bloodstream when called upon. That the obese have less fat accumulating proteins than their leaner selves is also in contrast to TWICHOO. The leaner "after" folks here had a more fat-trapping milieu than their "before" situations. The lean generally trap fat very efficiently (though some with insufficient adipose tissue do not). Clearly, the individual components of what drives fat uptake/esterification and lipolysis/release, do not regulate the NET accumulation of fat. This study adds to the evidence in support of this statement.
Before I go ... speaking of Frayn ... If you're relatively new to the Asylum, you may hear his name bantied about here often, but I've not blogged all that much on his work of late. If you don't know what I was talking about just now, may I suggest the following older blog posts (in reverse chronological order): Fatty Acid Trafficking , Adipose tissue as a buffer for daily lipid flux ~ Keith Frayn 2002 , Non-esterified fatty acid metabolism and postprandial lipaemia , Insulin Resistance ~ Taubes v. Frayn.
I'm going to save my analysis of Keith Frayn's latest review paper for the new year, but the findings here dovetail nicely with Frayn's more recent thinkings on fatty acids. Specifically, that adipocyte IR on the release side (inefficient suppression of HSL ) may be less important in the etiology of metabolic syndrome and diabetes, but rather that the defect occurs at the uptake side of the equation. This leads to inappropriately elevated basal circulating free fatty acids as well as inappropriately elevated postprandial NEFA with the composition of said fatty acids being potentially troublesome. Both lead to too much fatty acid storage in inappropriate places. Metabolically healthy lean individuals would have highly responsive fat tissue, presumably with sufficient FABP levels to whisk fat out of the bloodstream when called upon. That the obese have less fat accumulating proteins than their leaner selves is also in contrast to TWICHOO. The leaner "after" folks here had a more fat-trapping milieu than their "before" situations. The lean generally trap fat very efficiently (though some with insufficient adipose tissue do not). Clearly, the individual components of what drives fat uptake/esterification and lipolysis/release, do not regulate the NET accumulation of fat. This study adds to the evidence in support of this statement.
Before I go ... speaking of Frayn ... If you're relatively new to the Asylum, you may hear his name bantied about here often, but I've not blogged all that much on his work of late. If you don't know what I was talking about just now, may I suggest the following older blog posts (in reverse chronological order): Fatty Acid Trafficking , Adipose tissue as a buffer for daily lipid flux ~ Keith Frayn 2002 , Non-esterified fatty acid metabolism and postprandial lipaemia , Insulin Resistance ~ Taubes v. Frayn.
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