The oddity is the blip downwards of weight in canola fed rats, highlighted by the red oval on the graph:
Monday, November 04, 2024
Rapeseed oil for weight loss (3) Canola oil vs butter round two
The oddity is the blip downwards of weight in canola fed rats, highlighted by the red oval on the graph:
Sunday, November 03, 2024
Rapeseed oil for weight loss (2) and butter for obesity round one
This is the next paper. These people are good. Really good. There is almost nothing amateurish in this paper:
A highly saturated fat-rich diet is more obesogenic than diets with lower saturated fat content"The present study tested canola, lard, and butter, respectively, low, moderate, and rich sources of SFA, widely consumed in the human diet, in an animal model of dietary obesity. As predicted, results confirmed the hypothesis that an SFA-rich diet is more obesogenic than diets with lower SFA content."
Saturday, November 02, 2024
Have you thought about electron transporting flavoprotein dehydrogenase and its substrate electron transporting flavoprotein?
The basic TLDR is that if you take fat adapted mitochondria they will be using mtETFdh to generate a significant proportion of their maximal oxygen consumption for ATP generation. This means that complexes I and II will be down regulated, so supplying electrons to these complexes cannot match the oxygen consumption which would be generated if mtETFdh was maximally active. We have no available direct supplies of electron transporting flavoprotein to supply FADH2 in the way that beta oxidation does. "Dysfunction" is actually an artefact of not inputting adequate electrons to the CoQ couple via mtETFdh.
This applied both to studies on high fat diets and studies on fasting. It implies extreme caution if one is to decide that high PUFA diets, when high in overall fat, do actually cause *any* mitochondrial dysfunction, if only tested using inputs from glutamate/malate or succinate.
So this has major implications as a generic "how to read a paper" factor.
The insight is based on the oxygen consumptions in this paper where "disrupted bioenergetics" are claimed.
Rapeseed oil‑rich diet alters hepatic mitochondrial membrane lipid composition and disrupts bioenergetics
I wrote this in the post about the above paper:
There is nothing wrong with these mitochondria. Bioenergetic are *not* disrupted, as suggested by the title of the paper. Let's dig deeper.
What is happening is that the study is taking mitochondria from fat-adapted rats and feeding them on either a complex I input or a complex II input. Fatty acids, even LA, make significant use of electron transporting flavoprotein (ETF) dehydrogenase as their input to the CoQ couple. Mitochondria adapt their electron transport chains to the substrates available. If mitochondria from rats fed 40% of calories from fat are significantly dependent on mtETFdh for input to the CoQ couple, and have down regulated both complexes I and II, then feeding the preparation on substrates specifically aimed at complex I or II will obviously produce sub-maximal oxygen consumption. Which is what happens under either state 3 respiration or FCCP uncoupling.
Under the "tickover" conditions of state 4 respiration the uncoupling from PUFA shows clearly.
Obviously, to restore visibly normal mitochondrial function, what's needed is a supply of reduced ETF to use as a substrate for mtETFdh. As supplied by beta oxidation. Sadly you can't just buy reduced electron transporting flavoprotein from Sigma Aldridge, so you end up with artifactual mitochondrial "dysfunction".
Friday, October 18, 2024
Rapeseed oil for weight loss (1): Norwitz vs Goodrich (eventually, scroll down if bored by the very long Protons preamble)
Hypolipidemic Activity of Peony Seed Oil Rich in α-Linolenic, is Mediated Through Inhibition of Lipogenesis and Upregulation of Fatty Acid β-Oxidation
More translation: "Mediated Through Inhibition of Lipogenesis and Upregulation of Fatty Acid β-Oxidation" actually translates as "reduced insulin signalling". If you can measure virtually everything but have no hypothesis to hang you facts on, you'll get nowhere.
At what level of intake this effect kicks in is difficult to determine but it will undoubtedly be lower for ALA than for LA.
Evidence for Electron Transfer Reactions Involved in the Cu2+-dependent Thiol Activation of Fat Cell Glucose Utilization
to generate this graph
"At sufficiently high concentrations, unsaturated fatty acids were able to induce acinar cells injury and promote the development of pancreatitis." [Not my typo].
Early- and late-onset complications of the ketogenic diet for intractable epilepsy
An increase in serum C18 unsaturated free fatty acids as a predictor of the development of acute respiratory distress syndrome
"The calculated ratios of serum free fatty acids (ie., the ratio of C18 unsaturated fatty acids linoleate and oleate to fully saturated palmitate, C16:0) increased and predicted the development of ARDS in at-risk patients."
Now, I have fundamental ideas about choice of lipid sources for weight normalisation. Those ideas are compatible both with the choices made by Tucker and those made by Nick. Both are correct in their diametrically opposed choices. They are both correct for bodyweight. But there are nuances. I like nuances.
Tuesday, September 03, 2024
Protons (77) Shulman PUFA and insulin sensitisation. Or not. Or so.
Over in the comments to the last post on metformin and Shulman's lab, Tucker pointed out that Shulman was an author (penultimate, so a senior author) on Nowotny et al's 2013 paper
Mechanisms Underlying the Onset of Oral Lipid–Induced Skeletal Muscle Insulin Resistance in Humans
which starts its discussion with the controversy about whether PUFA, particularly from soybean oil, induce insulin resistance or insulin sensitivity. The most contradictory paper they cite is Xiao et al from 2006. In my head I think of this as the Hot Chocolate or the Cocoa study, which I discussed here as pure Protons in a cup of hot chocolate:
Differential effects of monounsaturated, polyunsaturated and saturated fat ingestion on glucose-stimulated insulin secretion, sensitivity and clearance in overweight and obese, non-diabetic humans
Sunday, September 01, 2024
Metformin (16) The LaMoia Shulman review
"Taken together, these studies indicate that metformin’s effect to increase insulin-stimulated peripheral glucose uptake is secondary to improved glycemic control and reversal of glucose toxicity, which can mostly be attributed to metformin’s ability to directly inhibit hepatic gluconeogenesis and HGP."
My own turn of phrase was:
"It [metformin] *appears* to improve insulin sensitivity, lowering the plasma level of insulin and glucose, but this is because it inhibits hepatic gluconeogenesis via inhibiting mtG3Pdh. That drops hepatic glucose output and that is what lowers the insulin level." I'm slightly cautions about the glucotoxicity aspect.
Obviously he needs to take about four more steps backwards up the course of insulin resistance before he reaches perilipins and basal lipolysis. Whether he will ever go a step further beyond that and realise how linoleic acid controls the adipocyte size which controls the perilipins is possibly another order of magnitude further away. He also has zero concept that insulin resistance, which he notes is utterly preserved across all of those metazoan species which use insulin (which is most of us), is a functionally protective mechanism. As in here:
Insulin resistance is a cellular antioxidant defense mechanism
Until you realise insulin resistance is an antioxidant defence mechanism you will keep trying to "cure" it.
Sunday, August 25, 2024
Protons (76) Those D12492 fed mice (Speakman and Tucker again)
We are now in a position to explain the "hyperphagia" of mice fed high fat, high linoleic acid diets such as the D12492 used in the Schwartz lab.
Metformin Reduces Body Weight Gain and Improves Glucose Intolerance in High-Fat Diet-Fed C57BL/6J Mice
The mice were offered something very similar to D12451 (45% fat rather than the 60% fat of D12492) but we don't know from which company it was purchased or even if the lard included was from Japan or America. No gas chromatography was used this time so a best guess might be around 10-15% of total calories as LA.
Wednesday, August 21, 2024
Protons (75) Tucker; Speakman; Astrup and linoleic acid. And insulin sensitivity
Ep. 22: John Speakman—What Causes Obesity?
A very large part of the core discussion is contained within this paper, a massive collaboration, with Speakman as first author:
Polyunsaturated:Saturated Ratio of Diet Fat Influences Energy Substrate Utilization in the Human
You can clearly alter the RQ under fasting conditions, on a fixed food quotient diet, simply by altering the dietary fat from 2% of calories as PUFA to 10% PUFA, switching palmitate in or out to balance the PUFA, which was mostly linoleic acid. MUFA were kept constant, as were all other macros.
Clearly 10% of LA in the diet moves almost all subjects towards a "pre-obese" phenotype. In two of the eight this move was dramatic. It seems very, very likely to me that these two individuals are at serious risk of obesity in an omega-6 rich environment. Follow up weights over the years would have been lovely but was not remotely the purpose of the study.
Thursday, July 11, 2024
Protons (74) Arne Astrup and the formerly obese
Fat metabolism in formerly obese women
mostly because Table 3 confirms all of my biases by showing formerly obese women are exquisitely insulin sensitive, which is pure Protons:
Saturday, June 01, 2024
Protons (73) Spanish vs Canadian studies or 3% LA vs 10.3% LA
Distinctive postprandial modulation of beta cell function and insulin sensitivity by dietary fats: monounsaturated compared with saturated fatty acids
This is *not* demonstrating saturated fat induced pathological insulin resistance. Here the insulin "resistance" will simply stop you getting fat. I would define this as the "normal" response to an high fat meal, assuming a low linoleic acid based fat.
Now, there are problems with the study and the authors are to be congratulated on the result generated (though not on their conclusions of course), especially the composition and size of the meals they had to design to get there. But here we are looking at a dynamic response to a single meal. Is it possible to examine their important findings under more steady state conditions? Would the relationship of PUFA ingestion to pathological insulin sensitivity still hold?
Thursday, May 30, 2024
Protons (72) Humans: 8% LA vs 74% LA by sustained oral ingestion
Differential effects of monounsaturated, polyunsaturated and saturated fat ingestion on glucose-stimulated insulin secretion, sensitivity and clearance in overweight and obese, non-diabetic humans
Protons (71) Rats: 13% LA vs 61% (mostly) LA by infusion
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.