Regional Differences in Fat Tissue Fatty Acid Regulation by Insulin

Insulin Regulation of Regional Free Fatty Acid Metabolism

Alternate Title:  Why I had a fatter ass before low carb?  :-)

This study involved 26 healthy young (21-38) non-obese (BMI 18-27) individuals split evenly by gender.  Excluded were any medications known to influence FFA metabolism.  Radiolabeled palmitate was used as a tracer for FFA's.  

All studies were initiated in the 12 hour overnight fasted state and palmitate was infused for the duration of the study.  Patients received insulin infusions of different doses (3M & 3F per group) for 150 min following baseline determinations.  Controls received a saline infusion.  Blood samples were obtained from femoral vein and artery (leg) and hepatic (liver) vein.  This was to assess systemic (whole body), leg and visceral (splanchnic) rates of appearance of FFA's  (release from adipose tissue).

Below is the palmitate UPTAKE rate for leg vs. splanchnic (visceral)  regions for the different insulin infusions:

For all subjects, baseline plasma palmitate concentrations in the femoral artery, femoral vein, and hepatic vein were 133 ± 6, 147 ± 7, and 106 ± 6 µmol/l, respectively. Therefore, in the postprandial state, leg was a net FFA producer, and the splanchnic bed was a net FFA consumer. Figure 1 shows the net leg and splanchnic palmitate balance as a function of the insulin dose infused. At the highest insulin dose, the leg became a net FFA consumer, whereas the splanchnic region became a net FFA producer.

Insulin suppressed leg palmitate release in a dose-dependent fashion as compared with the saline control, achieving 77% suppression at the lowest dose infused and almost complete (93%) suppression at the highest dose. Although splanchnic palmitate release was also inhibited in a dose-dependent fashion, the lowest insulin dose did not significantly suppress splanchnic palmitate release below baseline values, and it was only 65% suppressed at the highest insulin infusion rate.  

The various flux (exchange), uptake and release rates are summarized in the table below: {click to enlarge}

At the risk of posting screen shots of everything in the article, below is the last of the bunch:

Leg (both legs) and splanchnic palmitate release as a percentage of total palmitate release is plotted as a function of insulin dose in Fig. 4. At higher plasma insulin concentrations, leg palmitate release relative to systemic palmitate release decreases, whereas splanchnic palmitate release relative to systemic palmitate release increases.

So fatty acids are released from leg fat at a relatively consistent proportion compared to fatty acids released from all body fat.  This proportion is reduced slightly as insulin increases.  However, at basal insulin levels the fatty acids released from splanchnic represent a smaller proportion vs. leg fat, but a much larger proportion with increasing insulin levels.  

I would dare say these observations are interesting!  On the simplest level, this demonstrates that insulin doesn't behave in the same manner in different fat depots.  

In summary, we examined the dose-response relationship between insulin and regional FFA release. Leg fat was found to be more sensitive to inhibition of lipolysis than was systemic lipolysis, whereas visceral fat is less responsive to insulin.   Moderate hyperinsulinemia appears to increase the proportion of FFAs reaching the liver from visceral, as opposed to systemic, sources. Our results have significant implications for understanding the effects of insulin on glucose/fatty acid interrelationships in humans.

Some parting thoughts as regards low carb diets and my personal experiences.  I've shared how my weight distribution has changed considerably since first doing Atkins now almost 14 years ago.  My legs/butt are considerably smaller compared to the rest of me now.  Indeed I can now fit my legs comfortably into pants I wore when I was some 40 lbs lighter than I am now from before I ever tried LC.  If it is true that I've lowered my insulin, FFA's have finally been released more preferentially from my thighs.

It doesn't escape me that the observations in this study seemingly counter the various low carb belly fat plans. This is just a hypothesis here, let me be clear.  But in many, particularly those going from a high-carb SAD-style diet, going LC - usually involving some sort of "quick start" VLC phase - weight loss is significant in early stages.  It is well known that visceral fat is preferentially lost first when we lose weight, which is probably why so many health benefits can be attributed to a loss of a rather modest 5-10% of weight even in the "morbidly" obese.  So it is not surprising that, in the short run, the rapid losses most experience on low carb coincide with rapid reductions in waist size.  My own husband experienced this.

But I've also shared that over the long haul, I've either retained more belly fat when losing on low carb over the longer run and seemed to gain in the belly.  Look at the first graphic again.  The lower the insulin levels, the greater the splanchnic fatty acid uptake!  It has not escaped the notice of some that many low carbers seem to still sport guts or seem to gain abdominal weight even eating low carb.  This is, of course, observation based on a non-random sample of pictures to be found.  But fatty acid uptake is most prominent when?  In the postprandial period.  Following a mixed meal or a high carb meal, insulin rises - by the top graphic this favors uptake to the leg fat (and though not measured directly, non-splanchnic upper body fat).  Eating a high fat low protein meal often produces little to no rise from basal levels.  Look at the left of the graphic.  Look where that fat preferentially goes.