Okay, time to think about whole body insulin sensitivity, adipocytes and insulin.
First the core process; adipocytes which are listening to insulin will post GLUT4s on their surface, accept glucose and do enough de novo lipogenesis to both store and release palmitoleate. The palmitoleate is a signal that there is plenty of glucose around, let's use it.
Adipocytes are accepting glucose for signalling purposes and DNL lipid formation, plus they are sequestering away whatever lipid is available from the diet. The core function of insulin is the storage of DIETARY fat under the influence of carbohydrate. Boy, that is an old post! But the fact that there is plenty of glucose around means that the body should maintain insulin sensitivity, to make use of that glucose. But DNL in adipocytes which are insulin sensitive makes you, err, fat. As Cao et al point out in their lipokine paper:
"Additionally, genetic or pharmacological manipulations that boost de novo lipogenesis in adipose tissue (even though this sometimes leads to expansion of the fat depot) are associated with improved metabolic homeostasis (Kuriyama et al., 2005; Waki et al., 2007)."
I think this is a long winded paraphrase of the Hyperlipid concept "Getting fat is bad when you stop".
Increased insulin sensitivity in adipocytes makes you fat. That's as you would expect.
Back to the ice pick rats with their acute onset insulin hypersensitivity in adipocytes. During rapidly increasing bodyweight (on a low fat diet) there is a marked increase in obesity with excellent insulin sensitivity. Ended by six weeks.
Ditto MSG rats, but for in 4 weeks rather than 6 weeks. Can't tell from the gold thioglucose abstract, but at least a few weeks. Probably depends on all sorts of minutiae.
While ever these rodent models are gaining weight they maintain insulin sensitivity because they are doing DNL to get fat. On a low fat diet increasing obesity means DNL, palmitoleate and the ability to run metabolism on glucose. Logical.
Only once a brain-damaged rat becomes obese enough does hyperinsulinaemia set in, with attendant glucose intolerance. By this stage adipocytes are insulin resistant so have reduced ability to respond to insulin, reduced GLUT4 expression and, presumably, reduced palmitoleate synthesis. From the adipocyte's point of view there is not a lot of insulin around, whatever the blood concentration might be.
Lets look at the converse to obesity:
What does a lack of insulin signify? No food (or no carbohydrate, pax protein). Starvation requires insulin resistance as an obligate state for survival. How much good is palmitoleate going to do you under starvation or ketogenic dieting? Not a lot, unless you enjoy dropping precious glucose in to muscles until you brain falls to pieces.
An adipocyte which sees no insulin will not generate palmitoleate. If it generates anything at all (doubtful) it will be palmitate. Releasing some residual palmitoleate from adipocytes is fine for a few days, as long as there is glycogen hanging around. By three days this will be gone and so too should the palmitoleate. You are now in to hard core survival driven insulin resistance.
That's where I live.
Adipocyte distension induced insulin resistance is completely different. Here the adipocytes see low insulin when there is a ton of it around. There is a ton of glucose around too. But an adipocyte acts as per starvation and does what would be absolutely the correct thing under starvation circumstances. It releases palmitic acid and stops generating palmitoleate. Doing this while the macroscopic organism is eating bagels and french fries is bad. It's bound to generate massive hyperinsulinaemia to normalise glucose in the face of a ton of palmitic acid.
I'm just wondering whether there is time to look at the C57BL/6 mice. Just briefly as there is a lot of Mickey to be extracted on this subject when we get to idiots in detail. Briefly:
By an utter quirk of metabolism the VMH of C57BL/6 mice breaks under high dietary fat levels. So they have access to ample dietary fat when their VMH is injured, by definition. They store this fat because sympathetic tone to adipocytes is acutely lost and adipocytes become exquisitely insulin sensitive. Fat falls in to adipocytes as soon as the injury occurs, probably within hours of eating some butter, almost any amount of butter, however small.
But the fat they store is dietary fat. No DNL. They do not need to gain fat by DNL as it is there in the hopper. Dietary fat falls in to adipocytes. Palmitoleate synthesis? When fat is distending adipocytes so fast they are leaking FFAs despite losing lipolytic sympathetic tone? There is a ton of dietary fat dropping in to adipocytes, this is what gets released as they distend. By day three C57BL/6 mice are systemically insulin resistant. Their palmitoleate levels will be low and palmitic acid levels high. They are just a modification of the ice-pick/MSG/gold thioglucose family, but the process happens at warp speed due to the availability of DNL-free bulk fat.
Even on high fat plus high sucrose diets humans do not injure their VMH, at least not immediately. But C57BL/6 mice do and they have taught me a great deal over the years, made me think a great deal too. But they are still just a model, as explicable as the rest of the models, from the insulocentric point of view.
Once you have enough data.
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.
I think we might go to PUFA and SCD1 in adipocytes before hepatic DNL in this series.
BTW It's nice to see people in comments being a post or two ahead! At least this isn't complete gobbledegook to everyone!