I've spent the last few days looking in great detail at this next paper. Mostly I'm interested in the effect of subcutaneous fat transplanted to the omentum/mesentery. It does Good Things, the title says it all. I'll probably post more about it soon:
Beneficial Effects of Subcutaneous Fat Transplantation on Metabolism
Even transplanting supplemetary monstrousvisceralfat to the omentum/mesentery of recipient mice improves their insulin sensitivity (admittedly ns). I like this research group. They are reporting data and don't seem to have a specific point they are trying to prove. The down side is that I think their CLAMS equipment, core to understanding certain aspects, didn't work very well. You can tell they feel the same way by the turns of phrase they use to describe some of their utterly inexplicable peripheral data like RQs. I'll call it the Kahn paper.
This next paper has Konrad as senior author. He has an agenda. Just click on the author to see his other publications. He knows monstrousvisceralfat is evil. He just needs the correct model to show this. This one hit paydirt:
The Portal Theory Supported by Venous Drainage–Selective Fat Transplantation
OK, let's compare.
Kahn's group transplanted epididymal fat in to the mesentery and omentum of recipient mice, this drains to the liver directly. By their surgical technique some of this fat will have also had systemic drainage. They waited for 12 weeks. They then ran an hyperinsulinaemic euglycaemic clamp. There was a modest (ns) improvement in insulin sensitivity. They checked the histology for macrophages, there were a few. They checked these for IL-6 production, it was minimal. Happy fat, happy mice, no hepatic insulin resistance.
Konrad's group also transplanted epididymal fat in to the mesentery of recipient mice. They waited for five weeks then did a clamp and showed marked hepatic insulin resistance. There was no increase in portal FFAs or liver triglycerides. They stained the fat for macrophages. There were loads. They checked for IL-6 production. There was loads. They did it all again but with IL-6 knockout mice. Minimal macrophages in the adipose tissue, obviously no IL-6, no insulin resistance in the liver.
To Konrad it's cut and dried. Visceral adipocytes cause hepatic insulin resistance using IL-6.
Kahn's group check for this and found nothing of the sort. What's going on?
It took me about 12 seconds on google to pull up this abstract. It's not terribly important but does bring home the functions of IL-6, there are many:
Essential involvement of IL-6 in the skin wound-healing process as evidenced by delayed wound healing in IL-6-deficient mice
IL-6 is deeply involved in wound healing. Obviously IL-6 does cause insulin resistance, we know from Konrad's study. And we know that all of Konrad's implants were inflamed and secreting IL-6 at the end of the study, five weeks after the surgery. Was that because visceral adipocytes are just evil and want to kill us with IL-6 or is it because the healing process after transplantation uses IL-6 and is incomplete at five weeks? What if they had waited another whole seven weeks before testing at 12weeks?
In Kahn's paper the beneficial effect of adipose transplantation showed best for SC fat placed in the mesentery/omentum. The benefits started to show in bodyweight and fat percentage at eight weeks and were more obvious at 12 weeks post op. The hyperinsulinaemic clamp at 12 weeks showed insulin sensitivity was improved, p less than 0.05 in this group. The visceral to mesenteric transplants were similar but not as marked, mostly p stayed above 0.05.
Kahn's paper was 2008. Konrad's was 2011. Who to believe? Who might have read whom and worked out a counter study? Perhaps the matter has now been pretty well settled by the surgeons mentioned in the last post (Oregon excepted)?
I think it is quite likely that over-distended adipocytes do produce IL-6. But you're not going to show this in normal mice eating normal chow.
Clinical aside. If a case with pancreatitis, underlying an acute abdomen, ends up as an ex-lap, you get to see the state of the omentum and mesenteric fat under necrotising pancreatitis conditions. It's not pretty. In view of IL-6 and insulin resistance it should come as no surprise that acute pancreatitis is associated with diabetes, which resolves as the pancreatitis does, assuming a good outcome. Not always, but it's well recognised. I think IL-6 as a cause of hepatic insulin resistance is very real. I also think it is total artefact in Konrad's paper but, if it could be made to happen as a direct result of severe obesity (about which we have no idea from Konrad's paper), I might consider it to be a messenger. Looks like this hadn't happened in the morbidly obese folks going under the knife.
I found a mini-review by that one group of successful omentectomy surgeons in Oregon, listing all of the omentectomy studies which have failed to improve insulin sensitivity (no explanation was offered), in which there is actually one very small study mentioned in which an omentectomy only was performed, removing just under a kilo of omental fat on average. That's a lot of omental fat in my book. Not only that, but the subjects were all obese and diabetic. I mean, visceral fat, hepatically drained, distended adipocytes, insulin resistance. How could an omentectomy fail? Spectacularly is the word and the authors say so point blank. I'd already decided I like these omentectomy-only surgeons before I found that three of them are part of Atkins Center of Excellence in Obesity Medicine. They might just share my biases!
Anyone wanting that last paper, it's here:
Surgical removal of omental fat does not improve insulin sensitivity and cardiovascular risk factors in obese adults
I particularly like the rise in HbA1c, statistically ns but clinically perhaps so...