tag:blogger.com,1999:blog-36840063.post9215242737404482010..comments2024-03-27T22:57:00.742+00:00Comments on Hyperlipid: The paradoxical fat mice (1)Peterhttp://www.blogger.com/profile/14527788116058656094noreply@blogger.comBlogger10125tag:blogger.com,1999:blog-36840063.post-79914091602464961742019-10-01T13:20:05.811+00:002019-10-01T13:20:05.811+00:00Peter: " NB adipocytes are utterly packed wit...Peter: " NB adipocytes are utterly packed with mitochondria. The lipid droplet is not "in" the cytoplasm per se. The cytoplasm is full of mitochondria."<br /><br />That is interesting, it paints a picture of adipocytes as 'dark satanic mills' --- big factories with lots of fires burning in the dark, smoky (ketones?) and dangerous oxidising chemicals stored in close proximity to flammable substances. <br /><br />But seriously, I should have been more clear that I was commenting on your reply to AltaVistas 40% corn oil observation ratger than the main topic. Mea Culpa.<br /><br />So what you say there about high insulin being a problematic result is in accord with what AltaVista is observing ( given whatever the other 60% of diet possibly is.) I'm a bit slow to catch on sometimes (obviously!) but my excuse is that this is a strange type of mental arithmetic. My understanding of the concept of pufa being unable to generate much insulin resistance is that, on their own, they provide more caloric input than any resistance they can generate will be able to manage ie inadequate negative feedback <br /><br />However, is it reasonable to think that when there is a lot of pufa being burned, pushing nadh without so much fadh2, but that is combined with a quantity of electrons inserted by eg mtg3pdh then there should be a suitably high level of qh2 in the pool to generate enough ret -> superoxide to generate adequate insulin resistance? Passthecreamhttps://www.blogger.com/profile/01214860448492630477noreply@blogger.comtag:blogger.com,1999:blog-36840063.post-41407374636500550242019-09-29T08:11:36.453+00:002019-09-29T08:11:36.453+00:00Pass, yes I think you are saying that it is the sa...Pass, yes I think you are saying that it is the same drivers which cause both insulin secretion and resistance. The two fit together and control the level of insulin and so control bodyweight. But the cost can be of elevated insulin and not all of insulin's signalling can be resisted. Also I think adipocytes, as eluded to by karl, will be the last cells in the body to resist insulin, especially if oxidising PUFA... NB adipocytes are utterly packed with mitochondria. The lipid droplet is not "in" the cytoplasm per se. The cytoplasm is full of mitochondria.<br /><br />PeterPeterhttps://www.blogger.com/profile/14527788116058656094noreply@blogger.comtag:blogger.com,1999:blog-36840063.post-79365598046458584002019-09-27T23:13:39.156+00:002019-09-27T23:13:39.156+00:00@Passthecream
The diet they ate is at https://www...@Passthecream<br /><br />The diet they ate is at https://www.envigo.com/resources/data-sheets/7012-datasheet-0915.pdf<br /><br />,.,.,.<br /><br />This demonstrates what I've been speculating about - insulin sensitivity is what matters more than insulin levels.<br /><br />I've also been thinking more about an adipocyte with a 2019 sized load of PUFA - the cell itself has to burn a bit of fat to power itself - would the change in insulin sensitivity effect LPL and HSL? (I think so?) - could there be some genetic variance in this effect? <br /><br />Remember:<br />LPL moves fat in to and HSL moves fat out of fat cells.<br />insulin is known to activate LPL in adipocytes<br />HSL is inhibited by insulin.<br /><br />,.,<br /><br />Another thought - I have a cat that has eaten little else than industrial chicken - full of LA - he is close to 10 years old - and not fat. My hunch is it is because he doesn't eat any carbs. So I'm speculating that it is the combination of a PUFA diet and the carbs that is fueling the T2D/obesity pandemic.karlhttps://www.blogger.com/profile/13490274388549702613noreply@blogger.comtag:blogger.com,1999:blog-36840063.post-51304212821152189512019-09-19T00:25:24.286+00:002019-09-19T00:25:24.286+00:00Hi Peter
I apologise in advance for my inability ...Hi Peter<br /><br />I apologise in advance for my inability to hold all the different pieces of this puzzle in my head, at the same time! <br /><br />The other 60% of AV's rat diet above would surely be key? For instance, if it was a significant % of sucrose. <br /><br />(Corn oil btw is approx 13% saturated fats and 27% mufa. )<br /><br />You would have this, quoting Protons(38)<br /><br />'' we also ought to think of the situation under a large, uncontrolled fructose input through mtG3Pdh occurring at the same time as saturated fatty acids are being oxidised. That gives us this scenario:<br />... ... squiggle ... ...<br />Having two inputs reducing the CoQ couple (as well as a little input from SDH) is a perfect recipe for driving extreme reverse electron transport through complex I with the production of completely unreasonable quantities of superoxide and H2O2. This is the scenario of free radical mediated damage combined with serious insulin resistance. D12079B anyone? The problems are less severe with PUFA fats ... ... "<br /><br />I am supposing that this would also give rise to significant insulin production in beta cells. Then there will be increased beta oxidation from the insulin resistance lowering the inhibitory effect of insulin on hsl and so on. <br /><br /><br />Can it be this simple or am I missing something?Passthecreamhttps://www.blogger.com/profile/01214860448492630477noreply@blogger.comtag:blogger.com,1999:blog-36840063.post-80925831486551550092019-09-18T09:04:01.448+00:002019-09-18T09:04:01.448+00:00Alta: https://high-fat-nutrition.blogspot.com/2017...Alta: https://high-fat-nutrition.blogspot.com/2017/02/protons-obesity-and-diabetes.html<br /><br />Have you looked at the adipocytes?<br /><br />PeterPeterhttps://www.blogger.com/profile/14527788116058656094noreply@blogger.comtag:blogger.com,1999:blog-36840063.post-62245554889765879282019-09-17T14:19:10.882+00:002019-09-17T14:19:10.882+00:00This comment has been removed by the author.Passthecreamhttps://www.blogger.com/profile/01214860448492630477noreply@blogger.comtag:blogger.com,1999:blog-36840063.post-19364932445740085832019-09-16T14:07:16.186+00:002019-09-16T14:07:16.186+00:00Hello Peter,
I was wondering because insulin is ne...Hello Peter,<br />I was wondering because insulin is necessary for the proper functioning of brain cells. Not for glucose uptake but excitability, regulation of appetite and fuel distribution and others. I was speculating whether these mutations still guarantee sufficient insulin for the brain during CR. These mice do not behave in a normal way. They are, as you implied, energy-deprived. <br /><br />They did not measure ketones. A pity.<br /><br />Anyway, I am looking forward to your next topic. <br /><br />BR<br />Alexhttps://www.blogger.com/profile/15567909385379524496noreply@blogger.comtag:blogger.com,1999:blog-36840063.post-35746814372500138622019-09-16T12:39:16.496+00:002019-09-16T12:39:16.496+00:00Hi Alex,
I believe both of the Ins genes in rats/...Hi Alex,<br /><br />I believe both of the Ins genes in rats/mice are probably whole animal expressed, certainly both are in the pancreas and it is in the pancreas that the visible adaptation to knockout occurs. This gives the idea https://www.genetics.org/content/178/3/1683 (not read all of it). The links at the start of the post are to the folks who developed the model. <br /><br />Exactly. Normal CR mice are hungry all the time and look for food. They will almost certainly have physiological insulin resistance to maintain normoglycemia in the presence of restricted food combined with extended periods of no food. Their ability to keep calories out of adipocytes and in the blood stream is in-tact so they remain functional.<br /><br />The post-torpor mice still have mildly elevated insulin at the 12 hour mark, though it’s lower than at the 4h mark. All ns of course. Hows and whys beyond GIP are an open question… You might get some answers by looking at insulin signalling rather than insulin levels of course but that would need a whole lot more mice.<br /><br />alta, unified theory: the holy grail….<br /><br />PeterPeterhttps://www.blogger.com/profile/14527788116058656094noreply@blogger.comtag:blogger.com,1999:blog-36840063.post-42160868788130628722019-09-16T11:39:18.163+00:002019-09-16T11:39:18.163+00:00Doesn't explain why my 40% corn oil mice have ...Doesn't explain why my 40% corn oil mice have 2x insulin and 5x leptin. Not a unified theory yet mwahahaaltavistahttps://www.blogger.com/profile/10443439015369042857noreply@blogger.comtag:blogger.com,1999:blog-36840063.post-75724905906982622502019-09-16T10:53:35.273+00:002019-09-16T10:53:35.273+00:00Greetings!
Do I get you right? Your theory goes l...Greetings!<br /><br />Do I get you right? Your theory goes like this: the difference between insulin states determines the effect of insulin on adipocytes. So, the threshold for "effectivity" is relative to baseline? Large delta, large effect (all exponential of course)? The one that eats mostly carbs will not suffer grave consequences when increasing insulin temporarily, but the keto-one will put on weight just by looking at ice-cream?<br /><br />How can Ins2-/- mice cope with this mutation? Is Ins2 not the mouse's brain variant of insulin? Does Ins1 compensate fully given CR? To what extent? <br /><br />It is weird that the mice show lethargy/torpor since CR mice without mutations do actually the opposite: they are a wee bit more active than ad-lib. Fig3F: CR mice move less (they point this out) That is strange. <br /><br />The higher insulin might, very carefully, suggest that physiological insulin resistance developed. Are the adipocytes greedy or just opportunistic? <br /><br />What if physIR coupled with insulin deficiency screws up the brain? Can the mice mount the appropriate low-energy stress response? It does not seem so.<br /><br />Best wishes!<br />Alexhttps://www.blogger.com/profile/15567909385379524496noreply@blogger.com