The APOE*3-Leiden mice were reared on non specific chow. At 12 weeks of age (Time -4) they were put on to something derived from the AIN-93M diet. All lipids were all supplied as methyl esters of fatty acids, not triglycerides. It contained 1.2% of calories as LA and 9% of calories as sucrose. The intervention group had exactly half of the 1.2% of LA calories supplied in the form of deuterium stabilised, ROS peroxidation resistant D2-linoleic acid.
Monday, May 16, 2022
Deuterium protected linoleic acid
The APOE*3-Leiden mice were reared on non specific chow. At 12 weeks of age (Time -4) they were put on to something derived from the AIN-93M diet. All lipids were all supplied as methyl esters of fatty acids, not triglycerides. It contained 1.2% of calories as LA and 9% of calories as sucrose. The intervention group had exactly half of the 1.2% of LA calories supplied in the form of deuterium stabilised, ROS peroxidation resistant D2-linoleic acid.
Sunday, May 08, 2022
Protons (70) Uncoupling does suppress insulin signalling
An example from 1988
Evidence for two independent pathways of insulin-receptor internalization in hepatocytes and hepatoma cells
Regulation of glucose transporter 4 traffic by energy deprivation from mitochondrial compromise
The Mitochondrial Uncoupler DNP Triggers Brain Cell mTOR Signaling Network Reprogramming and CREB Pathway Upregulation
"The protein levels of AKT, p-AKT (Thr308), ERK, and p-ERK were examined by immunoblotting which showed that the activated (phosphorylated) forms of these kinases (p-AKT and p-ERK 42/44) were reduced in the cerebral cortex at 24 and 72 h after DNP treatment (Fig. 3c–e). Collectively, these results suggest that insulin receptor signaling is suppressed in cerebral cortical cells in response to mild mitochondrial uncoupling."
Saturday, May 07, 2022
Protons (69) BAM15
Mitochondrial uncoupling attenuates sarcopenic obesity by enhancing skeletal muscle mitophagy and quality control
Identification of a novel mitochondrial uncoupler that does not depolarize the plasma membrane
and there is another group working with the same drug here
Mitochondrial uncoupler BAM15 reverses diet-induced obesity and insulin resistance in mice
"Collectively, these data demonstrate that pharmacologic mitochondrial uncoupling with BAM15 has powerful anti-obesity and insulin sensitizing effects without compromising lean mass or affecting food intake." My italics.
![]() |
Plasma concentration appears to be sub-therapeutic by four hours max, probably drops too low by two hours. The rest of Figure 1 shows us that BAM15 is essentially liver specific. To demonstrate that the uncoupling is liver specific you have to give that higher dose of BAM15 (50mg/kg) and measure tissue specific oxygen consumption at peak effect, ie one hour post gavage.
We can also see that by four hours after a therapeutic gavage that liver concentration is also sub therapeutic following a 50mg/kg oral dose:
Wednesday, May 04, 2022
Protons (68) Pathological ROS (1)
Too few ROS.
The core mechanism for the generation of excessive ROS under unmitigated LA oxidation is high delta psi.
Sunday, April 03, 2022
Monday, March 28, 2022
Linoleic acid panel discussion
Here's the link to the panel discussion about PUFA and obesity, hosted by David Gornoski.
My Big Fat Panel: How Seed Oils Cause Obesity - A Neighbor's Choice by David Gornoski
It was an interesting discussion but I'm not really sure we achieved any consensus as to how you would convince a mainstream scientist that we are correct...
Peter
Wednesday, March 16, 2022
Friday, February 18, 2022
Ioannidis
I'm also coming to accept that prison or sectioning for the primary malfeasants is not going to be the best or even a practical solution. Lessons still have to be learned and systems questioned.
Monday, January 31, 2022
How's it going, Pfi$rael?
Friday, January 28, 2022
Saturday, January 22, 2022
So you want some DHA? Chickens in Norway
Increased EPA levels in serum phospholipids of humans after four weeks daily ingestion of one portion chicken fed linseed and rapeseed oil
Thursday, January 13, 2022
Covid playground
This is just a "post" to allow comments between people interested in the current COVID saga more easily. Comments on all posts older than two weeks are to be moderated by myself, just to keep the spam under control. So here are two weeks of unmoderated commenting scope if people want to exchange comments if I'm off working or weekending with the kids.
There you go Eric. Good idea.
Peter
Wednesday, January 12, 2022
Rimonabant and adipocytes
Rimonabant and hemopressin
For those of us with an adipocentric/insulin based outlook on life Rimonabant is interesting. It takes about 30 seconds on PubMed to pull out
CB1 agonists make adipocytes insulin sensitive. Rimonabant blocks this effect, which made me feel good about Protons/insulin/obesity and I left the subject alone in a nice glow of confirmation bias for a few months.
Adipocyte cannabinoid CB1 receptor deficiency alleviates high fat diet induced memory deficit, depressive-like behavior, neuroinflammation and impairment in adult neurogenesis
and a little wander to the Place-which-shall-not-be-named gets you the full text.
Nothing changes in the gut. Nothing changes in the liver. Nothing changes in the brain. The hypothalamic Reward™ dopaminergic neurons are left untouched. All that happens is that adipocytes lose (at least) the insulin sensitising effect of CB1 receptor activation. Weight completely normalises in less than a month. It's also worth noting that in control mice adipocyte CB1 gene deletion does nothing.
Saturday, December 11, 2021
Protons (67) a formula revised for butter oil
Docosahexaenoic acid lowers cardiac mitochondrial enzyme activity by replacing linoleic acid in the phospholipidome
Butyrate: A Double-Edged Sword for Health?
Conclusions totally depend on how you set your study up, what you consider good and what you consider bad. Bear in mind that butyrate is the darling of fibre-philes so consider publication bias too. Conversely it is to a large extent consumed by the colonic epithelium, so not a lot gets through to the systemic circulation. But some clearly does. The snippet of Figure 2 which caught my eye was this section:
Wednesday, December 08, 2021
Protons (53) a formula revised
Tuesday, December 07, 2021
!Kung Bushmen and mongongo nuts yet again
Alpha-eleostearic acid (9Z11E13E-18:3) is quickly converted to conjugated linoleic acid (9Z11E-18:2) in rats
This 9c, 11t CLA is exactly the same isomer as rumenic acid, the primary CLA of ruminant meat/dairy fats.
Conjugated Linoleic Acid Supplementation Reduces Adipose Tissue by Apoptosis and Develops Lipodystrophy in Mice
Bear in mind this is a model and has been set up to produce an extreme black/white result and it delivers.
"The semipurified diet was a low-fat diet and on a calorie basis contained 63% carbohydrate, 11% safflower oil, and 26% protein. Safflower oil was used as a source of fat. Safflower oil (high-oleic type) contained 46% oleic acid (18:1 n-9) and 45% linoleic acid (18:2 n-6) from total fatty acids. CLA was prepared as a free fatty acid at Rinoru Oil Mills (Nagoya, Japan) and stored frozen in plastic bottles blanketed with nitrogen. Linoleic acid was isomerized to CLA with isomers (34% c9, t11/t9, and c11; 36% t10 and c12; 3% c9, c11/c10, and c12; 2% t9, t11/t10, and t12 from total fatty acids). In the CLA-fed group, to keep fat intake constant in the 2 groups, 25% of the safflower oil was replaced with CLA"
That's a quarter of 11% of calories as mixed isomer CLA, the sort you might take as a supplement, ie around 3% of calories. About a third of this is the active 10t, 12c CLA, ie around one percent of calories.
Comparison of dietary conjugated linoleic acid with safflower oil on body composition in obese postmenopausal women with type 2 diabetes mellitus
they were using 6.4g/d mixed CLA isomers. That will be around 3g/d 10t, 12c CLA. That's exactly the ball park used to produce lipodystrophy and diabetes in mice. The same phenomenon occurs in pigs where after slaughter back fat can be extracted, weighted and processed to detect apoptosis:
Supplementation with conjugated linoeic acid decreases pig back fat deposition by inducing adipocyte apoptosis
Monday, November 29, 2021
Are you on clenbuterol? (3)
More from Risérus
Trans fatty acids and insulin resistance
"This is especially true [inducing insulin resistance] for conjugated TFA, i.e. conjugated linoleic acid (CLA), which clearly impairs insulin sensitivity."
I think is reasonable to assume that Risérus expects ordinary trans fatty acids to impair insulin sensitivity too, though not quite as effectively as CLA does. He just needs a big enough intervention study to prove it.
Clenbuterol-Induced Insulin Resistance in Calves Measured by Hyperinsulinemic, Euglycemic Clamp Technique
Basically it's looking at acute treatment with a lipolytic agent. Here are the glucose infusion rates under an hyperinsulinaemic clamp:
Clenbuterol prevents epinephrine from antagonizing insulin-stimulated muscle glucose uptake
Sunday, November 28, 2021
Are you lino-philic? (2)
"Taken together, the evidence suggests that replacing saturated fats and trans fatty acids with unsaturated (polyunsaturated and/or monounsaturated) fats has beneficial effects on insulin sensitivity and is likely to reduce risk of type 2 diabetes. Among polyunsaturated fats, linoleic acid from the n-6 series improves insulin sensitivity."