tag:blogger.com,1999:blog-36840063.post3965893203104896421..comments2024-03-29T06:45:45.894+00:00Comments on Hyperlipid: Speculation on the effect of subcutaneous adipocytes implanted in to the mesentery of micePeterhttp://www.blogger.com/profile/14527788116058656094noreply@blogger.comBlogger6125tag:blogger.com,1999:blog-36840063.post-68767127199897860912018-06-11T12:15:55.163+00:002018-06-11T12:15:55.163+00:00Somewhat unrelated:
https://www.theguardian.com/s...Somewhat unrelated:<br /><br />https://www.theguardian.com/society/2018/jun/10/converting-bad-fat-to-good-fat-a-new-means-of-tackling-obesity<br /><br />How do 50 - 100 g of brown fat, which probably contain less mitochondriae than several kg of muscle or 1.4 kg of brain, manage to burn through 20% of daily calories??Erichttps://www.blogger.com/profile/15626165768870660952noreply@blogger.comtag:blogger.com,1999:blog-36840063.post-58374291257935291902018-05-29T08:31:26.073+00:002018-05-29T08:31:26.073+00:00Hi Wooo, As you well know I have a horrible blind ...Hi Wooo, As you well know I have a horrible blind spot on leptin. I looked at figure 3A where leptin is very low in the systemic circulation and just thought “Well, they’re skinny…”. We’d be talking implanted adipocyte/liver leptin crosstalk here (?) which is out of my field of reading. I hadn’t considered an increase in exposure to insulin. Obviously the insulin in the HPV is much higher than in the systemic circulation. The question then becomes one of asking where the arterial supply to the transplants arises from (mesenteric artery? i.e. systemic?) so I’m still not sure… I have to admit that I was expecting that the portally released FFAs, if they are real, would induce hepatic insulin resistance but the portal infusion data look to be at much lower rates than the rates supplied by whole body lipolysis under starvation, where hepatic insulin resistance should occur. So if the effect is via portal FFA the effect should require low-but-not-zero supplementation from the SC adipocytes.<br /><br />I also looked at the 14C-DG uptakes in Fig4 but these only show basal vs (what I assume is supra maximal, it’s not in the methods) insulin. Probably tells us nothing except how much “room” is present in a given adipocyte in each population, rather than physiological responses during rising/falling insulin levels. All of the transplanted SC adipocytes stay small, transplanted VIS adipocytes grow very slightly, but they are pretty big to being with.<br /><br />It’s certainly an interesting paper which opens up all sorts of ideas. I think the authors have a long way to go.<br /><br />PetePeterhttps://www.blogger.com/profile/14527788116058656094noreply@blogger.comtag:blogger.com,1999:blog-36840063.post-86568293566005212062018-05-28T22:30:36.630+00:002018-05-28T22:30:36.630+00:00One more thing, SQ adipocytes close to portal circ...One more thing, SQ adipocytes close to portal circulation will also be exposed to more insulin attenuating lipolysis, but more importantly, provoke exaggerated leptin synthesis.<br /><br />I think FFA is unlikely to be mechanism as the rodents had superior glucose tolerance and reduced hepatic glucose output, which usually would not occur if there was a greater shift to fat metabolism, but it is highly consistent with a leptin effect as leptin is enormous in regulating hepatic glucose output. Leptin treatment alone can controlt ype 1 diabetes which is largely mediated by disinhibited glucagon. But this is expected if SQ adipocytes in mesentary were making more leptin, particularly right near the liver.ItsTheWooohttps://www.blogger.com/profile/12057537399918684119noreply@blogger.comtag:blogger.com,1999:blog-36840063.post-90706054451177371742018-05-28T22:21:42.450+00:002018-05-28T22:21:42.450+00:00Interesting
It seems adding SQ fat whether SQ or v...Interesting<br />It seems adding SQ fat whether SQ or visceral lowered wt, whereas SQ fat located messenteric was most effective to reduce wt. Its noted in rodents higher leptin causes linear and progressive wt loss, so i would assume the body wt reducing effects of higher adipocytes in rodents to mostly be a leptin thing, with an additional benefit of transplant close to portal circulation to enhance effect. <br /><br />Even though a hypothesis can be made adipocytes are dumping FFA producing satiety we also must account that insulin concentrations are higher near portal circulation, so subcutaneous adipocytes transplanted here will have more lipolysis suppression than if they were conventionally planted more peripherally. So, though subq adipocytes are more IR, they will be *less* lipolytic if transplanted to an area of the body with a higher insulin concentration. In other words SQ fat peripherally would be less antilipolytic, than SQ fat near portal circulation, due to a higher exposure to insulin. <br /><br />Another possible interpretation is perhaps increasing adipocytes so close to the liver may have a triglyceride lowering effect, an intervention which is noted to produce leptin supersensitivity. Extra normal adipocytes themselves will contribute to elevated leptin levels, combined with adding adipocytes with more insulin stimulation near portal circulation to better attenuate leptin-resistance promoting triglyceride excess. Its too bad serum triglycerides were not measured.<br /><br />Higher leptin level (more normal sized adipocytes) + lower triglycerides -> wt loss.<br /><br />It could as well just be an effect of higher leptin alone; assuming these were normal adipocytes, the level of leptin should increase, as would total body fat. Wt loss then occurs, consistent with leptin treatment of rodents.<br /><br />In humans who are normal increasing leptin does not really induce wt loss so i would expect SQ transfers in humans to just increase fat mass, although SQ in mesentery may correct dyslipidemia of TG excess that prevents BBB leptin transport, as it likely did in these rodents.ItsTheWooohttps://www.blogger.com/profile/12057537399918684119noreply@blogger.comtag:blogger.com,1999:blog-36840063.post-36892538719882643842018-05-28T15:06:28.083+00:002018-05-28T15:06:28.083+00:00Thanks cave, any other transpositions spotted woul...Thanks cave, any other transpositions spotted would be gratefully received!<br /><br />PeterPeterhttps://www.blogger.com/profile/14527788116058656094noreply@blogger.comtag:blogger.com,1999:blog-36840063.post-50370143287073491932018-05-28T14:08:56.546+00:002018-05-28T14:08:56.546+00:00The first two comments on this post are spam. Here...The first two comments on this post are spam. Here's hoping they are dealt with anon.<br /><br />Peter, I got a little confused in the last few paragraphs. I thought all the fat transplantation experiments were performed on mice? Not rats?<br /><br />"What was the augmentation of FFA supply to the liver from SC adipocytes in the mesentery of the operated rats in Kahn's study?"<br /><br />"I guess the third question is why the SC adipocyte recipient rats actually ate a little more than the controls in the CLAMS apparatus..."cavenewthttps://www.blogger.com/profile/08461541719892430585noreply@blogger.com