I have a certain, very specific, idea of how linoleic acid produces obesity. It seems as though relatively few people share this point of view. That is absolutely fine. Bright people have their own ideas and, eventually, if the core process is consistent, all views of the development of obesity and its associated insulin resistance will eventually converge. I spend a great deal of time thinking about whether linoleic acid enhances insulin sensitivity -> directly causing obesity or whether linoleic acid causes insulin resistance directly -> reactive hyperinsulinaemia -> obesity. The data make me favour the former.
This is the first paper I have come across where various fatty acid mixtures were assessed, in rats, for their acute effects on insulin sensitivity in vivo. In particular I was interested in the effect on glucose utilisation under hyperinsulinaemic euglycaemic clamp conditions. The higher the infusion rate, the more insulin sensitive the rat is.
They infused intravenous oil emulsions continuously for five hours and then continued throughout the exogenous hyperinsulinaemia over the following two hours, while clamping glucose at around 6.5mmol/l. So this is looking at normoglycaemia combined with fasting levels of FFAs until the clamp period. The rate of deliver per hour was roughly comparable to a 24h intake of calories for a rat of this size, averaged to an hourly rate.
Everything is fairly physiological until you add in the insulin/glucose infusions for the clamp while maintaining the lipid supply. Then you are looking at the situation where FFA supply cannot be suppressed by insulin, so you have a model for metabolic syndrome.
The results are quite clear. Whole body insulin responsiveness is suppressed by any fatty acid availability.
Clearly the glucose infusion rate, representing whole body insulin sensitivity, is lower in the SATU group (lard oil) compared to the PUFA group (soybean oil) but this is not remotely statistically significant (p = 0.2849). However there is no suggestion that linoleic acid is uniquely triggering insulin resistance compared to saturated fats, bearing in mind that modern (2015) Canadian lard is higher in insulin sensitising LA at 15% than my preferred fats such as beef tallow or suet which are around 2% LA (correctly ignoring any CLA content).
So the Protons concept could be suggested to have earned some marks here, there is more insulin resistance in the saturated fat group (GIR 43micromol/kg/min) when compared to the less insulin resistant linoleic acid infused group (GIR 73 micromol/kg/min). But not statistically significant.
However, there is no suggestion that linoleic acid per se causes enhanced insulin resistance, so causing obesity via secondary hyperinsulinaemia. In fact the trend is in the reverse direction.
In these rats.
Humans next.
Peter
6 comments:
Can saturated fat lead to obesity via reactive hyperinsulinaemia ?
Particularly with fat to carb (F:C) ratio ~1.
I wonder if you subscribe to Dr Kwasniewski's view that the macronutrient ratio F:C governs whether one develops obesity/metabolic syndrome or not.
Gyan, I doubt it. Over the years Protons has developed and I am left with pathological insulin sensitivity leading to obesity and MS secondary to non-limitable FFA supply from distended adipocytes. Without omega 6s I doubt any diet is obesogenic, with a few qualifiers around Surwit type diets.
Peter
What do you think about fructose and alcohol. As you mention before they are sort of the same, but is it leading to obesity?
John
So there is a puzzle - early stages of T2D there is an increase in insulin levels - at the same time inappropriately high insulin sensitivity in adipose tissue. Is it possible that we are seeing a response to control elevated FFA levels?
Frankly non of the current hypotheses leave me completely satisfied - not that they don't carry some truth. The problem in sorting out the competing narratives is more than one can be true at the same time. The question becomes which effect dominates? Is it 4-HNE or is it the proton switch? Or is it x, y, z etc..
The pancreas hypotheses overlook the fact that insulin goes up first - maintaining glucose control in the early stages. You can fix your diet to control BG - but the underlying dis-regulation appears to be permanent damage. That super high output of insulin might exhaust the pancreas and damage it is not the same as showing that the pancreas is what causes the disease. (We always have to tie down the direction of the arrow of causation).
I've wondered if it is possible that we are selecting maladaptive MT and end up with a sub population that is causative?
If it is agreed that the damage is permanent, in exactly which tissue do we find the damage? The liver has damage from fructose and LA - and the combination is synergistic for damage.
One thing that I'm quite certain of is that we still don't have definitive answers. On the other hand, avoiding novel foods seems a wise low risk preventative measure.
Amen karl.
Peter
"One thing that I'm quite certain of is that we still don't have definitive answers. On the other hand, avoiding novel foods seems a wise low risk preventative measure."
Truer words were never said.
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