Tuesday, November 11, 2008


Isoflavones block uptake of dietary cholesterol by macrophages in mice, but fail to cause a reduction of artherosclerosis.

"Soy protein containing isoflavones favorably influences macrophage lipoprotein metabolism but not the development of atherosclerosis in CETP transgenic mice."

How can they say that this had a favorable influence? If lowered uptake of cholesterol by macrophages had no benefit to the mice? ?

If you remove a mouse's ovaries, then feed her cholesterol, she gets artherosclerosis.

If you remove a dog's thyroid, and feed it cholesterol, artherosclerosis.

If you feed a bunny cholesterol, it gets artherosclerosis. This after all you did was add cholesterol to it's natural diet of corn starch cellulose and caseine protein. But if you make the rabbit type I diabetic by removing its pancreas, it fails to get artherosclerosis. Still in trouble, just no artherosclerosis. In other studies they avoided bunny heart disease by feeding them dessicated thyroid. In still other studies they just fed them iodine, and that worked against artherosclerosis.

A rabbit's natural diet is grass, bark, twigs. Grass is a rich source of vitamin k, beta carotene, and being a green vegetable, probably iodine. Did a multi-billion dollar statin industry grow out of studies on iodine-deficient rodents?

If you wanna avoid heart disease, get your hormones sorted out.

(The fact that women are less likely to get heart disease but more likely to get goiter--that's kind of suggestive, ain't it?)

Tuesday, November 4, 2008

I just found this book on Google Book Search; http://books.google.ca/books?id=taGpgaQ4Q7UC&pg=PA322&lpg=PA322&dq=fructose+carbohydrate+oxidation&source=web&ots=e8vxbZLWrW&sig=kfXOP6QMAY1JU1irZUApLifsqbE&hl=en&sa=X&oi=book_result&resnum=4&ct=result#PPA322,M1

The section I linked to talks about the effect of carb intake on carbohydrate oxidation; long story short, carb oxidation is maximized when glucose and fructose are taken together. Absorption rate is maximized with this mix, so there's just more to oxidize. (This is in humans for once.)

Calories taken in with an associated flavour can cause a preference for that flavour. Is that why glucose/fructose mixes, which would cause the quickest influx of carb calories, are the popular sugars? Fructose is sweeter; why don't they just put pure fructose in colas? Too sweet? Then why not use slightly less?

Potatoes were once sanctified for being complex carbs, the claim being that their structure caused a slow sustained absorption of carbohydrate. Then vilified for having a high glycemic index and just dumping glucose into the system. We're not back to saint status for spuds yet, but maybe the fact that they're mostly glucose limits the maximum rate of sugar absorption in the gut? As long as you don't eat them with honey?

I already posted about this study;


In which mice fed a high fructose (60 percent) became leptin-resistant. They were fed the fructose diet for 6 months, which didn't make them fat but increased their triglycerides. Then they were fed a high fat diet and this made them fat, but not control mice that never went through the fructose feeding. This went on for another two weeks. It would have been nice to see what happened on a longer high fat low fructose diet; whether the condition reversed itself.

As usual, kinda over my head. but does this relate to the failure of fructose to activate srebp's when compared to glucose?

The ability to regulate specific genes of energy metabolism in response to fasting and feeding is an important adaptation allowing survival of intermittent food supplies. However, little is known about transcription factors involved in such responses in higher organisms. We show here that gene expression in adipose tissue for adipocyte determination differentiation dependent factor (ADD) 1/sterol regulatory element binding protein (SREBP) 1, a basic-helix-loop-helix protein that has a dual DNA-binding specificity, is reduced dramatically upon fasting and elevated upon refeeding; this parallels closely the regulation of two adipose cell genes that are crucial in energy homeostasis, fatty acid synthetase (FAS) and leptin. This elevation of ADD1/SREBP1, leptin, and FAS that is induced by feeding in vivo is mimicked by exposure of cultured adipocytes to insulin, the classic hormone of the fed state. We also show that the promoters for both leptin and FAS are transactivated by ADD1/SREBP1. A mutation in the basic domain of ADD1/SREBP1 that allows E-box binding but destroys sterol regulatory element-1 binding prevents leptin gene transactivation but has no effect on the increase in FAS promoter function. Molecular dissection of the FAS promoter shows that most if not all of this action of ADD1/SREBP1 is through an E-box motif at -64 to -59, contained with a sequence identified previously as the major insulin response element of this gene. These results indicate that ADD1/SREBP1 is a key transcription factor linking changes in nutritional status and insulin levels to the expression of certain genes that regulate systemic energy metabolism.


I came across SREBP when I was digging around reading about leptin; they did a study a while ago where they fed mice a leptin-free diet, and the mice lost all of their body fat within a few weeks. Leucine is more famous for it's anti-catabolic effect, promoting protein synthesis in muscles.

Leucine is a keto-protein; it can be made into fat, but not sugar. Fat can be used to synthesize cholesterol and steroids and stuff, and so can leucine. The presence of certain sterols is important in the synthesis of fatty acids. (Just don't ask me which sterols!) You can see how a very low fat diet that is also low in leucine might lower the production of fat cholesterol and sterols, and might thus make it hard to produce the very elements necessary to synthesize fats that might be used in turn to produce fat cholesterol and sterols... That is, if I'm at all following the plot here.

Maybe the catabolic effect of marathon-type exercise is related to this as well? But this time in muscle instead of fat?

Heres another one;


Overexpression of sterol regulatory element-binding protein-1a in mouse adipose tissue produces adipocyte hypertrophy, increased fatty acid secretion, and fatty liver.
Horton JD, Shimomura I, Ikemoto S, Bashmakov Y, Hammer RE.
Departments of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9046, USA. Jay.horton@utsouthwestern.edu
Sterol regulatory element-binding proteins (SREBPs) are a family of membrane-bound transcription factors that regulate cholesterol and fatty acid homeostasis. In mammals, three SREBP isoforms designated SREBP-1a, SREBP-1c, and SREBP-2 have been identified. SREBP-1a and SREBP-1c are derived from the same gene by virtue of alternatively spliced first exons. SREBP-1a has a longer transcriptional activation domain and is a more potent transcriptional activator than SREBP-1c in cultured cells and liver. Here, we describe the physiologic consequences of overexpressing the nuclear form of SREBP-1a (nSREBP-1a) in adipocytes of mice using the adipocyte-specific aP2 promoter (aP2-nSREBP-1a). The transgenic aP2-nSREBP-1a mice developed markedly enlarged white and brown adipocytes that were fully differentiated. Adipocytes isolated from aP2-nSREBP-1a mice had significantly increased rates of fatty acid synthesis and enhanced fatty acid secretion. The increased production and release of fatty acids from adipocytes led, in turn, to a fatty liver. Overexpression of the alternative SREBP-1 isoform, nSREBP-1c, in adipose tissue inhibits adipocyte differentiation; as a result, the transgenic nSREBP-1c mice develop a syndrome resembling human lipodystrophy, which includes a loss of peripheral white adipose tissue, diabetes, and fatty livers (Shimomura, I., Hammer, R. E., Richardson, J. A., Ikemoto, S., Bashmakov, Y., Goldstein, J. L., and Brown, M. S. (1998) Genes Dev. 12, 3182-3194). In striking contrast, nSREBP-1a overexpression in fat resulted in the hypertrophy of fully differentiated adipocytes, no diabetes, and mild hepatic steatosis. These results suggest that nSREBP-1a and nSREBP-1c have distinct roles in adipocyte fat metabolism in vivo.
PMID: 12855691 [PubMed - indexed for MEDLINE]


One more study, quoted near the end of the last study;

Vol. 12, No. 20, pp. 3182-3194, October 15, 1998
RESEARCH PAPERInsulin resistance and diabetes mellitus in transgenic mice expressing nuclear SREBP-1c in adipose tissue: model for congenital generalized lipodystrophy Iichiro Shimomura,1,4 Robert E. Hammer,2,4 James A. Richardson,3 Shinji Ikemoto,1 Yuriy Bashmakov,1 Joseph L. Goldstein,1,5 and Michael S. Brown1
1 Department of Molecular Genetics, 2 Department of Biochemistry and Howard Hughes Medical Institute, 3 Department of Pathology, The University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75235 USA
Overexpression of the nuclear form of sterol regulatory element-binding protein-1c (nSREBP-1c/ADD1) in cultured 3T3-L1 preadipocytes was shown previously to promote adipocyte differentiation. Here, we produced transgenic mice that overexpress nSREBP-1c in adipose tissue under the control of the adipocyte-specific aP2 enhancer/promoter. A syndrome with the following features was observed: (1) Disordered differentiation of adipose tissue. White fat failed to differentiate fully, and the size of white fat depots was markedly decreased. Brown fat was hypertrophic and contained fat-laden cells resembling immature white fat. Levels of mRNA encoding adipocyte differentiation markers (C/EBP, PPAR, adipsin, leptin, UCP1) were reduced, but levels of Pref-1 and TNF were increased. (2) Marked insulin resistance with 60-fold elevation in plasma insulin. (3) Diabetes mellitus with elevated blood glucose (>300 mg/dl) that failed to decline when insulin was injected. (4) Fatty liver from birth and elevated plasma triglyceride levels later in life. These mice exhibit many of the features of congenital generalized lipodystrophy (CGL), an autosomal recessive disorder in humans. http://www.ncbi.nlm.nih.gov/pubmed/12855691?ordinalpos=64&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum

In the study itself, they mention that the plasma free fatty acids were not elevated; so they were not the source of the elevated triglycerides, and they suggest that free fatty acids synthesized in the liver itself went into those triglycerides. Do free fatty acids produced in the liver itself promote the production of glycogen and it's release? If the liver's ability to produce free fatty acids outstrips it's ability to produce triglycerides and this leads to increased blood sugar... Uh oh.

Sunday, November 2, 2008


This is an article about a study on type II diabetes treatment with a vegan diet. Neal Barnard of the Physicians Committee for Responsible Medicine was involved. The vegan diet improved blood glucose control and HBA1C levels when compared to the American Diabetic Association Diet.


There's also a 'cure' for diabetes video going the rounds, which has even found it's way deep into carnivore territory.

The video's about a raw vegan program, and makes more spectacular claims than the PCRM study--PCRM is talking improved blood glucose control, while Gabriel Cousens and others are talking cure--actual reversal of type II diabetes.

If you poke around on some raw vegan sites, you'll find some people with spectacular results.

Increased energy, spectacular weight loss, control of bipolar disorders. The list goes on and on.

Lots of good things to say about this diet, even if you don't necessarily buy into the explanation of the benefits given by those who enjoy them. Detox? I don't really follow you. Enzymes? The usual answer in carnivore (or just cooked food) circles seems to be that enzymes from the diet are broken down into amino acids in the stomach, and do the consumer no good as enzymes. But we release enzymes in our saliva, don't we? So it must be possible to benefit from enzymes, pre-stomach. And if dietary enzymes don't do anything, are just broken down into their component amino acids, then why are there studies that show benefits from consuming the pineapple derived enzyme, bromelain?

These people are eating food that belongs in the human diet, even if it's often lower in protein than most would consider desirable. Some of them may have serious honey or agave nectar habits, but I get the impression, mostly, from the blogosphere, that it is more common for raw whole foods to be the focus, whether fatty or carby, precluding most refined sugars from the diet.

There's another, non-vegan cure for Type II diabetes. It goes like this; feed mice or rats a choline-deficient diet. The rodents get fatty liver disease; excess buildup of triglycerides in the liver. This decreases free fatty acids in the liver. Free fatty acids encourage glucogenesis; which makes sense. When glucose is high, fat cells tend to synthesize glycerol, which acts sort of like a lynchpin to keep fatty acids in the cell. Glucose gets low, and less glycerol is synthesized, so that the breakdown of triglycerides predominates over synthesis; so that free fatty acids serve as a signal that glucose levels are low.

I got a lot of that from Wikipedia; I think most of it still stands, although I think that the increase in blood glucose from high free fatty acids in the liver is probably because of increased glycogen breakdown, because of a post Michael Eades did a while back about a colleague who traced glucogenesis in the liver and found that before finding it's way into the general circulation, newly formed glucose was formed into glycogen. I wonder if that's true of fats, too--are they first stored as triglycerides in the liver, before being released packaged as VLDL? Since there's such a thing as fatty liver disease, I guess that's probably true. If glucose isn't the proper endpoint, I guess we should probably just call it glycogenesis as well. So this must not just be a problem of glucose synthesis, but of glycogen breakdown, as well.

This also explains why rodents with visceral fat removed fail to get type 2 diabetes, even when genetically susceptible or when fed a diet that would normally give them type 2 (high fructose, for example.) And why it works also in humans, although they can't go to the extremes they go to with animals. Visceral fat is kind of close to the liver, and enjoys more blood flow than most fat tissue. It's a ready source of free fatty acids, and thus a steady source of encouragement to the liver to push blood sugar up.

Back to the mice; they get fatty liver from the choline-deficient diet. But no type 2 diabetes. Hooray.

Here's an interesting study that ties into this choline, fatty liver thing;


Mice that are fed a diet that is both choline and methionine free (and high in sugar) enjoy some curious therapeutic benefits; increased metabolism, weight loss (largely fat), increased fatty acid oxidation, and of course a nice fatty liver.

Not to put too fine a point on this, but it wouldn't be too hard to design a vegan diet that was low in both methionine and choline, would it? (Please don't start an online fat-loss clinic called fattyliverkins. Seriously.)

What we need isn't a diet that keeps visceral fat and liver fat from breaking down; we need something that reverses and prevents its excess accumulation.

Saturated fat protects against fatty liver disease, especially that caused by alcohol. Polyunsaturated fats don't, so you could imagine studies where saturated fat worsened blood sugar control when compared to polyunsaturated fat.

Saturday, November 1, 2008

This is cool. Ammonia is poisonous. Yeast in a potassium poor medium are poisoned by ammonia in that medium; nitrogen and potassium being similar enough for nitrogen to slip through a potassium channel if potassium isn't there to block it.