Thursday, August 30, 2012

Guess the weight of the mouse competition



Here's the Brownie points quiz.

What is the weight of either mouse?

If you find the answer, in this study, please let we know!

Peter

BTW you are allowed/obliged to scour results, discussion and all supplementary data. Please.

61 comments:

blogblog said...

Because nearly all of the (C57BL/6)mice are used at a young age and given inadequate exercise, the standard for the vast majority of lab research has been described as "a teenaged, alcoholic couch potato with a weakened immune system


http://www.slate.com/articles/health_and_science/the_mouse_trap/2011/11/black_6_lab_mice_and_the_history_of_biomedical_research.html

George Henderson said...

That's a good article - it starts here: http://www.slate.com/articles/health_and_science/the_mouse_trap/2011/11/lab_mice_are_they_limiting_our_understanding_of_human_disease_.html

I just realised today that most of the HCV research I read uses hepatoma cell lines.
http://www.virologyj.com/content/9/1/30/
Yet surely one purpose of HCV research would be to prevent hepatomas. It's probably a convenient, fast-breeding model, but how accurate is it really? Do these cells have normal amounts of functioning mitochondria, for instance? Is this why some current new drug trials are collapsing - because their anti-HCV drugs were developed in cancer cells?

George Henderson said...

The mice are better off than these humans:
http://www.kenes.com/easl2010/posters/Abstract221.htm

an AA-EPA ratio of 144? Help!

Results: The mean AA:EPA was 65 ± 34 reflecting a relative excess of n-6 PUFA overall. However, a broad range was noted from 15 to 144 AA:EPA. Dividing the group into quintiles of the reference range, 9 of the patients fell into the highest (5th) quintile (AA:EPA = 84 ± 30) compared to the remaining 6 patients (AA:EPA = 36 ± 16, p = 0.001). There was no statistically significant difference in the histological stage between these groups (fibrosis score = 2 ± 0.9 versus 1.7 ± 0.8) although the higher AA:EPA group was significantly older (55±12 versus 39±12, p=0.01).

Conclusion: There is heterogeneity of AA:EPA in non-cirrhotic NASH patients and an age-related increase in n-6 to n-3 PUFA evident in the AA:EPA ratio of erythrocyte lipids. Further work is needed to understand if this reflects dietary differences and how this might influence response to omega-3 fatty acid therapy.

George Henderson said...

P.S. is skinny mouse 20g, fat mouse 22g, approximately (from fig 3.C)?

blogblog said...

A coup[le of years ago I read a letter from an eminent researcher (name forgotten) who argued that virtually all medical research in the past 50 years was worthless becaue of the inappropriate use of mouse model.

Eva said...

Body weights in grams is given in fig 3. But what are they weighing? One is supposed to be fat pad weight but not sure on the others. Did they say how they ascertained fat pad weight? Adult rats weigh 300 grams or more so the other graphs can't be the whole rat. Maybe it's just late and I'm sleepy but I don't see any stats that would account for such obvious morphological diffs as between those two rats in the pic either. Seems like there was minimal smallish diffs between the groups. Always suspicious when they hide basic data and in this case, no apparent way to even backwards calculate the whole body rat weights either.

Nigel Kinbrum said...

Eva said...
"Adult rats weigh 300 grams or more so the other graphs can't be the whole rat. Maybe it's just late and I'm sleepy..."
Get some sleep. They're mice, not rats!

Fig. 1. states that the mice in the picture are 22 weeks old.

There are two types of people in this world: Those who can extrapolate from incomplete data

;-p

karl said...

Well I tried to find out who supplied the diet so I could look at the spec sheet and see just what the source of fats was? Can't find it - so I don't know if there was any crisco ( hydrogenated vegetable fats ) or how much sugar of what types.. I guess we are supposed to trust and parrot (thus fails a junk science test ).

I didn't find matching diets at http://www.testdiet.com/

Who else sells lab diets? ( found safe-diets.com - looks like there are many suppliers )

If I could see that this was a good study I would be quite interested.

I've been looking at some info that suggests that women with high BG during pregnancy give birth to children that tend to get fat.

I have a personal interest in this - my wife had gestational diabetes when she was pregnant with our two children - the first she controlled somewhat with diet - the second with insulin injections.

The first child is now 22 and mortally obese - ( I've failed at convincing her to eat low carb ) - the second (18 years old )is slender. ( Yes, I know that this is anecdotal, but that is why I would like to know more. )



Eva said...

Nigel, oops, LOL! Mice, not rats! Looking now, I can't find the HF4 weight for 22 weeks old mice. I cant' find any full weights for 22 weeks old. They show a photo of that fat mouse but I don't see any weight info on that group of mice at that age, not fat pad nor overall weight. For the chow rat, which I assume is the STD rat, they have fat pad weight for that age in fig 1, but not full weight. Seems rather confusing. They should just have one chart with all the numbers on it in one place.

I wonder what these poor sucker rats were actually eating. Assuming the chow was actually pieces of Food, what were the HF rats being fed. Was it Food or just chemicals? DId they measure the lengths of mice too? Maybe the HF rats grew bigger faster overall. I guess that was the point of measuring the fat pad.

But I am a bit confused about the fat pad measurements and how they were obtained. If there is a diff of say 800 mg in fat pad, is that a lot if the mice weigh 25,000 mg (25g)? It would only be a few percent difference in overall weight. Then they show a photo of a super fat and very trim mouse compared, but there is no weight data for these 22wk olds.

George Henderson said...

No no no!

This is about the mechanisms by which a high omega 6 lineolic acid intake drives obesity across generations.
It's certainly not junk science, it's trying to elucidate multiple mechanisms, which is a messy business.
As R. D. Feinman says, the high-fat diet is the rodent model that best corresponds to high-carbohydrate diets in humans.
They're not trying to prove that high-fat makes you fat, but show how too much omega 6 can make your children's children fat.

George Henderson said...

So these are the 4th generation: fat mouse has gained 2g per generation, so is now 8g fatter than skinny mouse...

"Morphology of representative male STD after four generations and HF4 mice at 22 weeks old"
- obviously the HF4 mouse is also 4th generation, or it would be old, grey and dead, as well as fat....

In our experiments, LA represented 18% and LNA 0.6% of the total energy intake compared with 5–7% and 0.8–1%, respectively, recommended for humans by expert committees on nutrition. Unfortunately, a significantly higher LA intake and much lower LNA intake are frequently observed in most industrialized countries.

karl said...

George Henderson said
"It's certainly not junk science"

May or may not be - the way things are left out of the paper may be 'tells' to the quality of the research.

Junk science can have correct results - just that I don't trust the results as much.

Things that I look for in a good paper - no missing details, all the information available to replicate the experiment, publicly archived data sets (via the web we hope ).

The children's children bit is hard to grasp. I'm thinking that if the insulin system gets broken - then high BG during pregnancy - which breaks the set point of the child - so the next generation breaks the set point even more?

But I don't know the type of carbohydrate used in this paper..

George Henderson said...

Carbohydrate is usually glucose, dextrin or such.

I agree the paper is poorly written. It's as if they had so much data they couldn't get it all in. Maybe there will be a second paper from the same experiment.
And maybe the journal's editorial, the replies, or a future review will clarify the picture.

It looks as if adipocyte expansion is the mechanism.
In evolutionary terms omega 6 PUFAs (and fructose) mark times of plenty, windfall seasons when it's appropriate to store fat.
This plenty isn't meant to last for a year, let alone many lifetimes.

George Henderson said...

n-6 fatty acids and adipogenesis

George Henderson said...

Above is a review by the senior author of the "guess the weight" paper.
It's all about prostacyclins.

Mechanism of prostacyclin-induced potentiation of glucose-induced insulin secretion.

karl said...

That is a pretty big change in interleukin 6 gene expression? .. 2.56 fold .. via table 2 - yet levels via fig 4 don't seem to match??

What would have happened if they added some O-3fish oil which is supposed to block O-6 => ARA production?

This is of great personal interest to me - I HAD quit elevated Lp(a) (more than 3 times the normal limit) and followed Dr. Davis's advice to try high O-3 6G/day ( that is 6 fish-oil pills BID - or 12/day -- ( I moved on to liquid and take 4ml AM and PM )).

The result is a long term effect - I'm now in the normal range. I think Lp(a) is an immune response and blocking ARA production is the key.

On http://wiki.xtronics.com/index.php/Heath_effects_of_different_fatty_acids you can see a chart of O-6 content with butter and coconut oil at the low end.

I wonder why avocados and guacamole are held as such health foods when they are full of O-6 ?

karl said...

There is a further connection here - IL6 which is elevated might be what causes elevated Lp(a)..

From some of my old notes near the top of http://wiki.xtronics.com/index.php/Lp%28a%29

It has been shown that Lp(a) is an acute-phase reactant, more than doubling in concentration in response to the proinflammatory cytokine IL-6

I've come to believe that it isn't fat that causes CAD - it is the O-6 content of the fat.

George Henderson said...

Yes, fish oil is so popular today precisely because it is the antidote to n-6.
"Trick and Treat", in the words of Barry Groves.
Or, the junk food - health food Axis of Evil.

The carbohydrate content of the diet modulates conversion of ARA (AA was obviously in need of a TLA) to prostacyclin.
Voleck and Westman have a paper showing ARA is highly conserved in VLC dieters (presumably with higher PUFA diets). There is a lot in the membranes but it is not being mobilised.
Thus fats such as avocado, free-range lard and olive oil, where n-6 is a relatively low proportion of total fat (9-11%), are not the problem. A smaller amount of a higher-PUFA oil in a fried potato might be.
n-6 ARA could be your friend in a very low-carb milieu.

Peter said...

George wrote "I agree the paper is poorly written" and gets the consolation prize for most understated criticism of a paper ever. Needless to say I have been unabke to locate any related paper on pubmed from the same group. So data are limited to a "need to know" basis, determined by the group leader. There are some interesting ideas buried, I assume deliberately, in the paper. Several statements are very, very carefully phrased. Some to the point of bent-ness.

Also, bit of an aside, a lot of the n numbers are scarily small. A bit more mouse-sex would have gotten a lot of p's below 0.05 that didn't get there on n=3 group sizes. Can you do stats on n=3????? I have had my wrists slapped for trying to do this in the past...

Peter

ItsTheWooo said...

@Karl
According to certain experts, gestational diabetes is helpful for fetal growth so your 22 year old child needs to ELMM. Ketogenic pregnancies are dangerous. Your wife's diabetes = healthy. The real question is why your 18 year old child isn't stunted or fat having her blood sugar exposure suppressed from crossing the placenta via maternal insulin injections. THATS THE REAL QUESTION, why isn't your 18 year old like a dauer worm all fat and thrifty like?

Also, according to all of the paleo elite crew the only difference between modern americans and traditional/ancestral people is that traditional people are eating low reward diets. The rest of us lardos need to ELMM. There is absolutely nothing else different about the metabolic endocrine or neurotransmitter situation of modern vs traditional people. The fact most pregnant women are overweight/ obese with hyperglycemia while pregnant (if not frank diabetes ) = irrelevant to mass epidemic of glucose intolerance. PSEUDOSCIENCE WOO WOO JUNK.

The fact that we can all plainly observe metabolic disorders progressively worsening in every generation is only evidence food is more rewarding than ever. Prenatal blood sugar and endocrine milieu is just not a factor. A bunch of naturally thin caucasian doctors from upper class stock with thin mothers who ate macrobiotic diets while pregnant told me so.

So like, the fact my cousin was a thin child and developed obesity/prediabetes at 25-30, and was very badly diabetic while pregnant with her son, is irrelevant to her son's health. He was born thin and a healthy little boy, not even LGA, until he was about 5 years old, at which time he became severely obese with clear signs of hyperinsulinemia and abnormal energy generation/lethargy for a little boy. It was so obvious even the dullard pediatrician told my cousin to take him to an endocrinologist (she didnt btw, too neurotic).

It was like overnight this child went from being thin and normal and energetic, to being extremely fat and tired with acanthosis and chronic hypoglycemia. It was like what happened to me over a series of years in my later childhood, except it happened to him in months in early childhood.

This is rather similar to his mother, who was a hyper *stick thin* child, ate like a horse, and a thin adult, but at 27ish? BAM! FATTRUCK. Mitochondria explosion, pretty obvious. The only difference is age of onset. Much younger for her son, exposed to a severely diabetic womb with hyperglycemic palcental blood.

All this means is that they all need to ELMM. The fact his mitochondrial explosion happened in childhood, whereas hers happened in her late 20s/early 30s, only means he was eating rewarding food earlier. Even though his mother, being slightly crazy, is a food nazi and refused to feed him anything but rice and apples and chicken (she later stopped the chicken) for fear of multiple allergies, is totally irrelevant. The ultra high reward diet of apples and rice and some chicken caused this boy to become super obese by gradeschool. Toxic environment again.


You're welcome, Karl. This is why I get paid so much by my financiers government and industries... because I think of the good science so you don't have to.

George Henderson said...

Has anyone eaten tempura-style japanese food?
You basically have bland, unrewarding food (chicken, fish, the worst rice in the world) made highly palatable through food chemistry, frying and fermentation of soy - no spices.
How does that fit in to FRH?

Anyway, back to reality, does anyone know of a culture with a high n-6 to n-3 ratio diet that does well? The kitavans of seed oils? Anyone?

Pacific islanders have the world's highest rate of obesity today. They don't have many MacDonalds franchises, but they do eat plenty of canned fish packed in soy oil, and they have only been exposed to grains for 200 years or so.
I often shop where they shop and notice the most popular convenience foods are cabin breads and biscuit, spam, and aforesaid canned fish. There are long aisles of these products.

blogblog said...

A nice non-technical summary of the role of n-6 FA in obesity by Will Lasek MD.

http://www.psychologytoday.com/blog/why-women-need-fat/201205/why-are-we-eating-so-much-more-we-used

blogblog said...

@George Henderson,
Are you aware that extreme obesity is considered a sign of beauty in Polynesian culture?

Pacific Islanders have been eating HUGE amounts of carbohydrates (sweet potatoes, tapioca, fruit, sugar cane etc) for thousands of years.

blogblog said...

@George Henderson,

A Pacific Islander with a BMI of 35 ("morbidly obese") typically has LESS body fat than an Asian Indian with a BMI of 25 ("healthy").


Br J Nutr. 2009 Aug;102(4):632-41. Epub 2009 Feb 10.
Body size, body composition and fat distribution: comparative analysis of European, Maori, Pacific Island and Asian Indian adults.

http://www.ncbi.nlm.nih.gov/pubmed/19203416

George Henderson said...

There's some truth in that, in some cases, but maori weren't overweight till recently, Pacific Islanders weren't diabetic.
It's a real problem here, and can't be explained away as healthy variation when it's a major occupation of the health service dealing with the consequences.

I never said PI didn't eat carbs; I said they didn't eat grains.
Not one grain that I know of is native to these parts.
Wheat is murder.

Breadfruit, taro and kumara are only a problem after you get diabetes.

There's no edible fruit native to New Zealand beyond some berries, no sugar cane, no grains.
in fact, if you plan to get most of your energy from carbs you will die easily in the New Zealand bush.

George Henderson said...

Will Laseck says:

There is also another clue from an unusual form of vitamin E that is especially abundant in corn and soybean oils. The level of this odd vitamin in our blood tells how much corn and soybean oil we are eating; and the higher the level, the more we weigh.

This would be gamma-tocopherol:


http://www.ncbi.nlm.nih.gov/pubmed/15230997

In older women gamma-tocopherol and gamma-tocopherol:alpha-tocopherol ratios were directly related to indices of obesity.
(they misinterpret the link in this absract)

http://www.ncbi.nlm.nih.gov/pubmed/20534324

gamma-Tocopherol levels were significantly higher in obese individuals (P < .05), whereas alpha-tocopherol levels did not differ among BMI subgroups

Good hint that supports the n-6 hypothesis.

George Henderson said...

Here's another:

In contrast to carotenoids, both plasma levels of gamma-tocopherol and lipid-adjusted gamma-tocopherol were significantly higher with obesity compared to those with BMI < 30.

CONCLUSION: Plasma alpha- and beta-carotene and beta-cryptoxanthin were negatively associated with obesity, whereas gamma-tocopherol measures were consistently elevated with high BMI.

http://www.ncbi.nlm.nih.gov/pubmed/20534324

Eva said...

George, yes, I often used to joke that I could eat any kind of gross tasting vegetable if they only fried it in tempura first. Must be some good drugs in that tempura mix! But chicken and fresh fish, I are easy to make tasty. You just need a pan, butter, and heat. Fish is interesting also because it tastes so so much better fresh. I wonder if the blah defrosted fish at the US stores is even all that healthy. If you get a fresh fish right out of the lake and eat it, the difference is incredible and tempura would be almost a crime!

George Henderson said...

About the Pacific Islands diet; I find very few mentions of sweet fruits native to the South Pacific.
I live here and only know of breadfruit (starch - delicious) and noni (a medicine), no doubt there are others but if they were staples they would be in the shops here.
It may be that where there are enough poisonous fruits, the safe ones are not discovered or developed. These islands have only been inhabited for a relatively short time.
In fact, pre-European South Pacific populations were not living in their evolutionary environment at all; they were relatively recent migrants from coastal China and Taiwan.

Eva said...

I think Taro was native to many pacific islands. Anywhere there was bamboo, they probably ate those corms too as most are edible. They think a lot of other kinds of fruits came around 3000BC from trade, including bananas, coconut, etc. They grow like crazy with all the heat and rain. If you go to the local markets on many islands, there are tons of sweet fruits available. Most have been grown there for a long long time, 100s of years at least. If the islanders were not fat a few hundred years ago, I don't think it's likely the blame of fruit alone. Some skinny cultures eat lots of fruit. I suspect fruit is OK by itself but a prob when combined with other concurrent probs.

George Henderson said...

I'm not saying fruit is a factor.
But bananas, the sweet fruit you mention, is a post-European import, mainly from the Victorian era plantations.
Coconut floats so is native to the islands.
I think islanders of the south pacific had very little exposure to fructose and this explains the high level of gout in these populations today.
They also had low intakes of omega 6 - most fats were saturated or omega-3 from fish.
And zero grains or legumes.
And in this context, carbohydrate from starchy roots and breadfruit was easily tolerated.

blogblog said...

None of the traditional Polynesian foods except kumara (sweet potatoes) can be grown in NZ because of the temperate climate.

The NZ Maori were living in a permanent state of semi-starvation (and constant brutal warfare due to a lack of resources) when Europeans arrived. This was due to a lack of land mammals and edible plants.

However in many tropical regions of the Pacific native fruits including papaya, several citrus species (and sugar cane)were widely cultivated before European settlement.

Extreme obesity (BMI>>40)was relatively commonplace in Hawaii when Europeans first arrived. It was observed that some women were so fat they couldn't even stand up.

George Henderson said...

The papaya (from Carib via Spanish), papaw, or pawpaw is the fruit of the plant Carica papaya, the sole species in the genus Carica of the plant family Caricaceae. It is native to the tropics of the Americas, and was first cultivated in Mexico[1] several centuries before the emergence of the Mesoamerican classical civilizations.

Sugar cane: Native to the warm temperate to tropical regions of South Asia (includes Indonesia and maybe PNG)

Here we have a citrus from melanesia: http://en.wikipedia.org/wiki/Citrus_macroptera

Hawaii, maybe, that's outside my jurisdiction:
But Fiji, Tonga, Samoa, Tahiti, Cook Islands?

I'm not saying there's no native fruits, just that I live in NZ and have never heard of them.

George Henderson said...

The Melanesian citrus:
The pulp of the fruit is greenish yellow and dry (does not produce much juice). The juice is very sour, and somewhat bitter.

Yum!

You know, people turn to cannibalism for a damn good reason.

Blogs we'd like to see:

Mark's Daily Apple:
Cannibalism - Is It Paleo?

LeonRover said...

Hey George.

"Long Pig" was the main treat in the victory feasts of many Pacific inter-island wars of the nineteenth century.

My source ?

R M Ballantyne's "The Coral Island", which whiled away many an hour in my boyhood reading.

Slainte

George Henderson said...

Great book! My favourite as a boy, definitely.
The Fijian economy in particular binged on cannibalism to an extent only otherwise seen in parts of equatorial Africa; the Maori usage was more controlled and varied; Tahiti not at all.
We really need a good paleo cannibalism essay, as nothing demonstrates the importance of fatty meat in the human diet so much as people eating each other.

Eva said...

Human, it's what's for dinner! Might be kinda hard to source it though. I think I'll stick with pork. ;-P Think about it though when you say 'turn to cannibalism.' That's mostly a cultural thing. In some cultures, it's just another meat source that is not bad tasting or even it is considered a source of spiritual power or sharing of the soul. One tribe even eats their own dead relatives as a way for those people to kind of live on. (remember the story of Kuru) If such is the belief system, starvation is not needed to 'turn to' cannibalism, although I am sure starvation can often have a heavy hand in any decision making process as well! ;-P

George Henderson said...

I recommend:
http://en.wikipedia.org/wiki/This_Horrid_Practice

blogblog said...

The Polynesians and Melanesians traveled and traded over the entire Pacific for thousands of years. They had access to a vast array of foods including pigs, dogs, chickens, coconuts, bananas, sago, tapioca, breadfruit and sugarcane etc).

The Maori were isolated from the rest of Polynesia for over 500 years. The only traditional Polynesian food eaten by the Maori was sweet potato.

In other words the Maori (including Cook islanders) were completely atypical of the Pacific Islands with regard to diet.

George Henderson said...

True. The early Maori had dogs and Moas too, later had chicken-sized flightless birds like the weka to eat - and some hunted seals and whales. But there were not the trade routes everywhere, many populations were effectively isolated. New Caledonia seems to be the limit of melanesian trade. If the islands had sugar cane, then we are looking at n-6 and cereals as agents of disease.
But then, why the modern incidence of gout?
The island banana is cooked green as a starch (I have some in the pot with my lamb & pork cassarole right now).
You can be sure I'll do more digging on this.
Where did you get the data from?

karl said...

pacific island food always makes me think of durian. I never thought I would end up liking it - it has a very strong sulphur smell - like the scent in natural gas. Sadly, I now avoid it as it is a really high carbohydrate food.

http://ndb.nal.usda.gov/ndb/foods/show/2520?fg=&man=&lfacet=&count=&max=25&sort=&qlookup=durian&offset=&format=Full&new=1

http://en.wikipedia.org/wiki/Durian

blogblog said...

Karl,

the durian must be the most overrated "food" on the planet. It tastes like burnt onions, has he texture of runny custard and smells like dirty socks.

blogblog said...

@George,
there are hundreds of possible variables beyond cereals to explain the poor health of modern Polynesians eg alcohol, low social status, lack of physical activity, dairy foods, changed gut microbiota etc etc.

O Numnos said...

@EJE

Just read your last post on the previous thread with great interest as much of what you wrote chimed with a recent experience of my own, although not releated to "sweet-spot" carb consumption.

In order to lose "that last few lbs of body fat" I had been drifting from a CKD through hard-core VLC to what I now (but not at the time) know would be termed a Protein Sparing Modified Fast as described by Lyle McDonald and others. Initially I was doing this PSMF in a 2 day on/1 off cycle. After about 3-4 weeks I developed a host of symptoms some physical some emmotional/psychological the severity of which waxed and waned - at the most extreme I honestly thought I was having some kind of breakdown. I noticed that the symptoms got worse if I consumed any alcohol which lead me to reactive hypoglycemia - the symptoms by now had continued for several weeks, after considering virus/detox symptoms as increasingly unlikely I finally came across Lyle's description of the PSMF and realized that at 90g/day I was not getting enough protein to cover gluconeogenesis. I added one tin of tuna/day and bingo the symptoms vanished in 2 days.

Of course I was hypocaloric and active so drinking additional water and you are correct about Sodium - I have to purposely add more than looks good for me or I get dizzy spells/severe orthostatic hypotension.

The really weird thing is the persistence of the symptoms, if I'd gone on a pure water fast I'd have felt like crap for 2-3 days then come out the other side feeling OK - whilst having my muscle catabolised presumably - why this apparently didn't happen is slightly puzzling (and illustrates the potential pitfalls of extreme diets).

blogblog said...

@O Numnos,

the healthiest body fat level is around 15% for men and 25% for women. There is no benefit (and usually health problems) being leaner.

There are very few low-carb hunter-gather societies. Hunter-gatherers are slender not highly muscled like bodybuilders

George Henderson said...

@ blog blog,
the take home lesson from this discussion for me has been that seed oils are more potently disruptive of fat storage than they've generally been given credit for.
The Pacific Islands model has its limitations, but it does give us many populations without diseases of civilization until quite recently.
We don't have to hypothesize about Paleolithic vs Neolithic, the facts are on record, and the pre-European diet isn't complicated by any of the Neolithic Agents of Disease.
The Kitavan story seems to show that smoking on island diets doesn't cause obesity or diabetes.
Diseases of civilization are not restricted to poorer or lower-status members of these communities, but increased pathology among the poor does match the greater reliance on cheaper foods.
And you know what foods those are.

mnature said...

Both mice actually weight the same. The one on the left got out of the cage, and was run over by a laboratory cart, so it is just a little squished out.

Chip Spitter said...

Hello Peter,

I had been trawling through your Lp(a) posts from years past and subsequently searched for any new studies on pubmed. It seems there is still uncertainty as to Lp(a)’s ultimate role but a couple of studies caught my eye. One that supposedly showed a relationship between low levels of Lp(a) and an increase in all cause mortality. http://www.ncbi.nlm.nih.gov/pubmed/22485129

The message I got from this was: Low Lp(a) = bad. As you had eluded to a couple of years ago.

Another here - http://www.ncbi.nlm.nih.gov/pubmed/22850646 suggests that marmots are considered good test subjects for studying Lp(a) these days. The poor buggers were fed an “atherogenic diet” of lard and corn oil. Why they bothered with lard is anyone’s guess, and the details on the diet were almost non-existent, but I guess you could speculate that corn oil makes the poor marmots Lp(a) shoot to the moon. Or it could have been the lard. I had to scratch my head as to the purpose of this one, other than deciding whether marmots were suitable test subjects.

Lastly, in your 7 Feb 2010 post you succinctly wrote of Lp(a): "It preferentially accumulates oxidised lipids and binds them in a form where they cannot be immediately excreted from the plasma. It also puts a great big sticky label on them that allows them to firmly bind to damaged tissue."

Is there anything you've seen since that would suggest why?

Cheers.

karl said...

@Chip Spitter

It is probably a bit more complicated - I keep explaining to people that the lipoproteins appear to be part of the innate immune system and CAD in most people is likely a type of autoimmune disease.

Lp(a) is part of this system - it didn't evolve to cause CAD. There is a normal range that Lp(a) is in and too low may be a sign of a lack of a compromised immune system. Yet, consistent high levels ( Like mine was - 3x past the upper bound ) is pointing to some kind of systemic inflammation.

It is well known that infections, surgery can cause a temporary high Lp(a).

So is it that diets high in fructose and O-6 end up breaking our immune and insulin systems?

As per https://www.jstage.jst.go.jp/article/expanim/61/4/61_461/_pdf Characteristics of himalayan marmots and their response to an atherogenic diet.

One group (4 males and 4 females) was fed HFCD, which contained 0.3% cholesterol, 6.7% lard, and 3.3% corn oil per weight in standard chow diet.

But the contents of the standard chow goes unlisted. My understanding is they are mostly herbivores but will eat a bit of bugs and meat if it comes their way. We don't know what the source of carbs was in this study.

George Henderson said...

There's a view that the immune system is just a bunch of stuff cobbled together, not some grand design.
This is consistent with the way lipoproteins have been drafted into it.
For example, the C3 protein, which is the lynchpin of the complement cascade, is made by a gene that also codes for lipoproteins
http://coolinginflammation.blogspot.co.nz/2009/01/scp-c3-and-lipid-metabolism.html

karl said...

Blogger George Henderson said...

There's a view that the immune system is just a bunch of stuff cobbled together

Actually, all of biology is like that - This theme is one of the reasons we know it wasn't designed - it evolved. So we have reuse of things for multiple purposes that want to evolve in different directions at the same time - where an engineer would realize that the radiator cap and oil filler cap need to be separate designs.

This, by the way, also predicts that transcribing the genes is the easy part - figuring out how it works is a real mess.

IcedCoffee said...

@blogblog,

I've heard the 15% and 25% numbers thrown around as optimal a few times, but I've never seen any non-epidemiological support for them. I'd be interested if you had more info to shed on the subject.

As a side note, I always wonder how much the refinement of the oils plays into these results. Would we see the same problems if the high O-6 was coming from something like nuts? I seem to recall some African Hunter gatherers who got a large amount of calories from Mongogo nuts (or something like that).

George Henderson said...

What you find is that nuts tend to be processed by heating when eaten in large quantities.
For example paleo sites in Britain show signs of mass roasting of hazelnuts. This would have increased shelf life by destroying some long-chain fatty acids, and improved digestibility by breaking down lectins.
Here's a classic post by Kurt Harris on the
Mongongo nut

"the egg-shaped, velvety fruits ripen and fall between March and May each year" - Wikipedia

The nuts are seasonal, so excess of n-6 would not accumulate. It's year round access to the accumulating effect that is dangerous. Much the same probably also applies to fructose - fattening in the windfall season under the combined triggers of linoleic acid and fructose seems highly adaptive to me. Eating them all year long is just messed up.

Breckenridge said...

I hope I can ask this question here... I keep hearing "you need carbs to burn fat" meaning its impossible to use fat as fuel without any sugar. Is this true?

annlee said...

@ Breckinridge:

Consider the Inuit ... the Masai ... the Buffalo People of the North American Plains ... etc. It's a myth, though a well-traveled one.

Peter said...

mnature, you get a prize for possibly being closest to the truth, though we'll never find out unless they do eventually publish some weights!!!!

Chip Spitter, not really. There is a limit in how much interest I can sustain in anything as stupid as lipidology. There is absolutely no doubt in my mind that oxidised sterols are used to signal repair processes which are subsequently labelled as diseases. There are an apparently infinite supply of folks out there willing to blame lipids for everything. I just get tired of the idea...

Peter

blogblog said...

@annlee

"Consider the Inuit ... the Masai ... the Buffalo People of the North American Plains ... etc. It's a myth, though a well-traveled one"

The real myth is that Inuits, Masai and Great plains Indians didn't eat plant foods.

The bison hunting culture of the Great Plains began about 1730 and ended around 1870.

Manne (1972) showed that Masai men aged over 40 had severe atherosclerosis.

Chip Spitter said...

Thanks Peter and Karl. I admit that, while your views make more sense to me, unfortunately I sometimes find myself reacting illogically to the scribblings of said lipidologists.

I do see that they all have their “tell” i.e. the jargon-camouflaged leaps of faith they make in their vehemently espoused views.

I guess it would be nice to have all the answers. I’m just not keen on entering politics or the clergy. Or becoming a nutritionist for that matter.

George Henderson said...

The Plains Indians didn't hunt Bison on horseback before they had horses; however, I've read an account from the 1700s in which Algonquin slaughter bison en masse at close range. The large animals of the New World were not afraid of man and his weapons until they were nearly hunted to extinction. And all the giant species became extinct in the narrow time band after the arrival of man in the Americas, in a pattern closely following his migrations.
Algonquin were famous for eating meat, yet their word "esquimaux" meant "meat-eater", so they obviously didn't consider themselves the biggest carnivores around.
Everyone eats protein and fat, with a little gluconeogenesis and ketogenesis, when they're fasting, so of course it's the normal default diet. If you needed carbs to burn fat you'd not be able to fast (night starvation - it's a pathological state only).

George Henderson said...

Stephan Guyenet has guessed the weight of the mouse, with some success after an initial setback:

"Now let's discuss the piece de resistance: the two studies that reported that feeding mice a diet with a poor omega-6:3 balance (excessive omega-6) caused a multi-generational obesity phenotype (16, 17). I was planning to discuss those studies in my AHS talk, so I revisited them to make sure they were solid. Unfortunately, I discovered serious flaws in both papers that fatally undermine the authors' conclusions. The short version is that neither study was properly controlled to come to the conclusion that omega-6:3 balance influenced fat gain. Both studies compared diets that differed in many ways, and that fact was not reported straightforwardly. In retrospect, I feel misled by these papers. I should have read them more carefully, and I apologize to my readers for that. As there is already too much misinformation on the internet, I've taken the post down."
http://wholehealthsource.blogspot.co.nz/2011/08/seed-oils-and-body-fatness-problematic.html

Peter said...

Ah, the Good Doctor again. "I don't like the data, I'll ignore it". As insightful as a turnip. As I would expect!

Peter