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Lowering insulin to limit de novo lipogenesis in adipose tissue.

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  • Lowering insulin to limit de novo lipogenesis in adipose tissue.

    What do you think, are there any distinct advantages to doing this? Could it be more beneficial somehow at the cellular level? Trick question?


  • #2
    Adipose tissue de novo lipogenesis

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    • #3
      I read that this morning, too. I wonder how people reconcile the apparent benefits of adipose DNL with the belief that we should "keep insulin low" for health purposes. Added to the fact that the more damaging liver DNL is not substantial compared to the DNL in adipose tissue, so it would seem the general benefits of spiking insulin outweigh the "risks".

      De novo lipogenesis and stearoyl-CoA desaturase ... [J Biol Chem. 2010] - PubMed - NCBI

      "DNL may not act primarily to increase fat stores but may serve as a key regulator, in tandem with elongation and desaturation, to maintain cell membrane fluidity and insulin sensitivity within the human adipocyte."

      One more: Modulation of palmitate-induce... [Am J Physiol Endocrinol Metab. 2011] - PubMed - NCBI

      "Overall, these data support the hypothesis that enhanced MUFA synthesis via upregulation of SCD2 activity can protect β-cells from elevated saturated FAs, as occurs in prediabetic states. Overt type 2 diabetes is associated with diminished islet expression of SCD and Elovl6, and this can disrupt desaturation of saturated FAs to MUFAs, rendering β-cells more susceptible to saturated FA-induced ER stress and apoptosis."

      Yep yep. I was wondering why the research on DNL seemed to drop off after 2004. It didn't drop off, it just branched off. My only question is how this all relates to dietary palmitate.

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      • #4
        I thought that might be what prompted ya . I really will have to study it a bit. After reading the article a few times I'm getting what they are saying to a degree, but I definitely need to do some further reading for my own understanding. I do note that liver DNL is bad (fructose/PUFA overload?) but peripheral white adipose tissue upregulation of DNL is good. The upregulation of DNL in caloric restriction kinda confuses me though.....as they point out this is counterintuitive. I'll read your links there, but my question to you is does a low insulin diet upregulate or downregulate DNL at the adipose tissue? And we would have to agree on what we call "low insulin" though. Are we talking ketogenic diet, IF'ing, or general low carb. Sort of cumulative vs insulin highs sort of question? I know what I might think it does, but I was wrong in the case of caloric restriction.

        I mean we could have a "low insulin diet" based on cumulative amount of insulin by only eating one meal a day even if that meal contained plenty of carbohydrate right? In fact many argue that this is part of the reason higher carb societies have no issue...they only eat a couple times a day vs. persistently spiking several times and keeping levels elevated.
        Last edited by Neckhammer; 01-04-2013, 12:47 PM.

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        • #5
          Just read this Hyperlipid: Protons: de novo lipogenesis. I think if your looking for a "how do you reconcile this...." then this would be part of it. I'm not saying one way or another. I do know that there are plenty of other physiological indicators for longevity and health though. Its vastly complex and no I don't think you can boil it all down to only insulin either.

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          • #6
            Everything our bodies can do benefits us. It's just whether those things are happening in excess or deficit or somehow incorrectly that is the problem.
            Female, 5'3", 50, Max squat: 202.5lbs. Max deadlift: 225 x 3.

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            • #7
              Originally posted by sbhikes View Post
              Everything our bodies can do benefits us. It's just whether those things are happening in excess or deficit or somehow incorrectly that is the problem.
              This board needs a like button.

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              • #8
                Originally posted by sbhikes View Post
                Everything our bodies can do benefits us. It's just whether those things are happening in excess or deficit or somehow incorrectly that is the problem.
                This is exactly what Peter was getting at in that link above:

                "To summarise: Palmitoleate is released by adipocytes when glucose and insulin are plentiful. Palmitate is released when glucose is sparse and insulin is low.

                The sh!t hits the fan when glucose and insulin are plentiful but adipocytes are so distended that they THINK glucose and insulin are low. When both insulin and glucose are high you want palmitoleate. If your adipocytes give you palmitate under these circumstances you had better have a pancreas of steel or diabetes here you come."

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                • #9
                  I'll respond in full later, but that blog of Peter's didn't reconcile anything. He said adipose DNL makes you fat. Perhaps in a mouse it does because DNL is a more significant pathway, and I have a study saved on my computer that says as much. Would anyone like to read it? Maybe if Gary Taubes had read it he wouldn't have proposed his ridiculous alternative hypothesis.

                  Evelyn blogged on this as well. The Carb-Sane Asylum: De Novo Lipogenesis ~ Another Case of an Undeserved Bad Reputation?
                  Last edited by Timthetaco; 01-04-2013, 03:56 PM.

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                  • #10
                    Originally posted by Timthetaco View Post
                    I'll respond in full later, but that blog of Peter's didn't reconcile anything. He said adipose DNL makes you fat. Perhaps in a mouse it does because DNL is a more significant pathway, and I have a study saved on my computer that says as much. Would anyone like to read it? Maybe if Gary Taubes had read it he wouldn't have proposed his ridiculous alternative hypothesis.

                    Evelyn blogged on this as well. The Carb-Sane Asylum: De Novo Lipogenesis ~ Another Case of an Undeserved Bad Reputation?
                    The problem is looking at any one thing out of context. And in this particular case it seems there is a lot left to uncover. I know for certain I haven't looked at all the data, but the bit I see seems to be quite inconclusive at this time. I'm not sure what the push is here? So your saying that de novo lipogenesis is beneficial....but under what circumstances? Obviously when its produced via a low calorie diet it might be, but I would suspect that if your driving it up with an overfeed of carbs any sort of health benefit will be totally obliterated by the effects of glycation and hepatic DNL especially if a significant portion were to be from fructose. Even in those cases isn't it the high carbers position that as long as calories are in check higher carb diets don't induce DNL?

                    Then there is your one article that seems to imply eating saturated fats up-regulates DNL. Would this be the same set of circumstances? Paul Jamminet shows that many supercentenarians tend to eat diets high in SFA. Is this a portion of why that seems to promotes longevity? He actually even makes the comment in Carb-Sanes blog........ "Palmitoleic acid is made from palmitate. Palmitate can be obtained either from dietary saturated fat that is 16-carbons or fewer, or from DNL. So I guess you would conclude it is the 18-carbon or longer saturated fats that deprive the body of palmitoleate."

                    Until we can hash out the difference in the different states of up-regulation and what the effects are I'm really just kinda sitting back and soaking it in. It is very interesting and wasn't really on my radar before, so thanks for the post.

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                    • #11
                      I'm not sure what my point was, exactly. I just learned about adipose DNL last night, so I'm learning out loud and in public. :/ Peter's post seemed to insinuate that the DNL is simply a function of eating carbohydrates, so I'm not sure that dietary palmitate would restart the process.

                      I don't know, I'm going to bury my nose back in the research. I ended up very confused.

                      However, don't be dense about glycation and hepatic DNL. Glycation from hyperglycemia is a result of TOO LITTLE insulin, and the majority of intrahepatic fat in NAFLD is from NEFAs, not DNL (saw a study on that this morning). If you're a non-diabetic paleo dieter, the only fructose your body sees comes from fruit. I wouldn't worry about it.

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                      • #12
                        As to "being dense", I was only repeating from the original link that stated hepatic DNL leads to insulin resistance, non-alcoholic fatty liver, and raised serum triglycerides. I'm obviously not too concerned about any of this as a paleo dieter, but none of these experiments are being carried out on paleo dieters anyhow. So we are just inferring what they might mean to the average joe on the street or implications for health in general right?

                        Either way I'm not well versed in this area at all. Like I said wasn't even on my radar.

                        The glycation bit is an interesting statement. My understanding is glycation increases as blood glucose levels increase and is accelerated drastically by fructose. This can happen easily in conjuction with insulin resistance and hyperinsulinemia....so I suppose we are back again to overfeeding and metabolic syndrome.

                        Anyhow, it is definitely an interesting avenue of research. I was also just throwing my thoughts out on the web here.

                        Let us know if you come across anything that validates the thing about DNL being raised in calorie restricted mice and how that mechanism compares to the other methods through which DNL is up-regulated.

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                        • #13
                          you can boil it all down to only insulin either.

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                          • #14
                            Originally posted by Timthetaco View Post
                            However, don't be dense about glycation and hepatic DNL. Glycation from hyperglycemia is a result of TOO LITTLE insulin, and the majority of intrahepatic fat in NAFLD is from NEFAs, not DNL (saw a study on that this morning). If you're a non-diabetic paleo dieter, the only fructose your body sees comes from fruit. I wouldn't worry about it.
                            Kinda, sorta.

                            Glycation is the result of too much glucose floating around and reacting with things it generally has no business getting involved with. If you are hyperinsulinemic, you have bucket loads of insulin in your system, and high levels of glucose in your bloodstream because you are insulin resistant, and you are insulin resistant because your capacity for metabolizing glucose has long been exceeded. So, glycation and insulin levels positively correlate, unless you are an insulin dependent diabetic ( type I ).

                            I'm not sure you meant to say NEFA ( non-esterified fatty acids ) because that simply means any fatty acid that is not attached ( esterified ) to a glycerol backbone. You probably meant PUFA ( poly unsaturated fatty acids ) because a sure way to induce steatosis ( fatty liver ) is to poison you with Omega-6 PUFAs, where poisoning you simply means removing the Omega-3 component from the diet.

                            It is unclear that eating PUFAs in the environmentally prevalent ratio of 2:1 Omega 6 to Omega 3, but grossly overeating both ( MOAR fat, don't you know ) is significantly better for you in terms of steatosis, and I'm willing to bet that there is a not insignificant segment of the "paleo" crowd that interprets the ratio as being indicative that they should "eat MOAR fish oil!"

                            -PK
                            Last edited by pklopp; 01-10-2013, 08:48 AM.
                            My blog : cogitoergoedo.com

                            Interested in Intermittent Fasting? This might help: part 1, part 2, part 3.

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                            • #15
                              I didn't mean glycation was a result of low basal insulin levels, just an inappropriately low immediate insulin response. Obviously the issue in that case is the insulin resistance, not the fact that your body has to use insulin at all. I don't believe that's controversial. And I did mean NEFA. I pointed it out because of the study I had read with graphs showing only 20% or so of liver fat in patients with fatty liver coming from DNL. A lot of low carbers point to liver DNL as an example of carbohydrates being bad for the liver, but it accounted for a much smaller amount of liver fat than one would expect if carbohydrates were the problem. The paper I read specifically divided it between NEFA and DNL, so that's why I used the term like that.

                              Interesting about PUFAs. Has anyone quantified what it means to overeat PUFAs on a whole foods diet? Obviously seed oils are the main contributor in that regard, and I wouldn't see a problem shifting more toward seafood instead of land animals (not isolated fish oil).
                              Last edited by Timthetaco; 01-10-2013, 08:11 AM.

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