Scientists Alter Fat Metabolism in Animals to Prevent Most Common Type of Heart Disease - ScienceNewsline

Scientists Alter Fat Metabolism in Animals to Prevent Most Common Type of Heart Disease - ScienceNewsline

Published: April 22, 2014. By Johns Hopkins Medicine

Working with mice and rabbits, Johns Hopkins scientists have found a
way to block abnormal cholesterol production, transport and breakdown,
successfully preventing the development of atherosclerosis, the main
cause of heart attacks and strokes and the number-one cause of death
among humans. The condition develops when fat builds inside blood
vessels over time and renders them stiff, narrowed and hardened, greatly
reducing their ability to feed oxygen-rich blood to the heart muscle
and the brain.

In a series of experiments, described April 7 in the journal Circulation,
the Johns Hopkins team says it identified and halted the action of a
single molecular culprit responsible for a range of biological glitches
that affect the body's ability to properly use, transport and purge
itself of cholesterol — the fatty substance that accumulates inside
vessels and fuels heart disease.

The offender, the researchers say, is a fat-and-sugar molecule called
glycosphingolipid, or GSL, which resides in the membranes of all cells,
and is mostly known for regulating cell growth. Results of the
experiments, the scientists say, reveal that this very same molecule
also regulates the way the body handles cholesterol.

The Johns Hopkins team used an existing man-made compound called
D-PDMP to block the synthesis of the GSL molecule, and by doing so,
prevented the development of heart disease in mice and rabbits fed a
high-fat, cholesterol-laden diet. The findings reveal that D-PDMP
appears to work by interfering with a constellation of genetic pathways
that regulate fat metabolism on multiple fronts — from the way cells
derive and absorb cholesterol from food, to the way cholesterol is
transported to tissues and organs and is then broken down by the liver
and excreted from the body.

"Current cholesterol-lowering medications tackle the problem on a
single front — either by blocking cholesterol synthesis or by preventing
the body from absorbing too much of it," says lead investigator Subroto
Chatterjee, Ph.D., a cardio-metabolic expert at the Johns Hopkins
Children's Center. "But atherosclerosis is a multi-factorial problem
that requires hitting the abnormal cholesterol cycle at many points. By
inhibiting the synthesis of GSL, we believe we have achieved exactly

Specifically, the experiments showed that treatment with D-PDMP led to:

  • a drop in the animals' levels of so-called bad cholesterol or low-density lipoprotein, LDL;
  • a drop in oxidized LDL, a particularly virulent form of fat that
    forms when LDL encounters free radicals. Oxidized LDL easily sticks to
    the walls of blood vessels, where it ignites inflammation, damaging the
    vessel walls and promoting the growth of fatty plaque;
  • a surge in good cholesterol or high-density lipoprotein, HDL, known to counteract the effects of LDL by mopping it up; and
  • a significant drop in triglycerides, another type of plaque-building fat.
The treatment also prevented fatty plaque and calcium deposits from
building up inside the animals' vessels. These effects were observed in
animals on a daily D-PDMP treatment even though they ate a diet made up
of 20 percent triglycerides — the human equivalent of eating a greasy
burger for breakfast, lunch and dinner. In addition, the researchers
say, D-PDMP appears to precision-target the worst byproducts of aberrant
cell growth signaling, such as oxidized LDL and the activity of certain
chemicals that fuel vessel inflammation, without altering cell growth

D-PDMP, which is already widely used in basic research to
experimentally block and study cell growth and other basic cell
functions, is deemed safe in animals, the investigators say. For
example, animals in the current study had no side effects even when
given D-PDMP doses 10 times higher than the minimum effective dose, the
study found. The research team is currently designing a compound drug
with D-PDMP, which they soon plan to test in other animals and,
eventually, in humans.

Mice used in the experiments were genetically engineered to lack a
protein essential in the breakdown of fats and thus were predisposed to
atherosclerosis. The researchers fed the animals a high-fat diet over
the course of several months, but also gave a third of the animals a
low-dose of D-PDMP. They gave a double dose of the same inhibitor to
another third and placebo to the rest.

When scientists measured the thickness of the animals' aortas — the
body's largest vessel and one that carries blood from the heart to the
rest of the body — they found striking differences among the groups. As
expected, the aortas of mice that got placebo had grown thicker from the
accumulation of fat and calcium deposits inside them. The aortas of
mice on low-dose D-PDMP, however, were significantly thinner with little
to no obstruction. To the researchers' surprise, Chatterjee says, mice
eating high-fat foods and treated with high-dose D-PDMP had nearly
pristine arteries free of obstruction, indistinguishable from those of
healthy mice.

Next, the researchers measured how well and how fast blood traveled
through the animals' blood vessels. Slower blood flow signals clogging
of the vessel and is a marker of atherosclerosis. The vessels of mice
fed a high-fat diet plus D-PDMP had normal blood flow. Mice receiving a
high-fat diet without D-PDMP predictably had compromised blood flow.

When researchers examined cells from the animals' livers — the main
site of fat synthesis and breakdown — they noticed marked differences in
the expression of several genes that regulate cholesterol metabolism.
The activity of these genes is heralded by the levels of enzymes they
produce, Chatterjee says. Mice treated with D-PDMP had notably higher
levels of two enzymes responsible for maintaining the body's delicate
fat homeostasis by regulating the way cells take in and break down
cholesterol. Specifically, the scientists say, the inhibitor appeared to
stimulate the action and efficacy of a class of protein pumps in the
cell responsible for maintaining healthy cholesterol levels by
transporting cholesterol in and out of the bloodstream. In addition,
mice treated that way had higher levels of lipoprotein lipase, an enzyme
responsible for the breakdown of triglycerides. A deficiency in this
enzyme causes dangerous buildup of blood triglycerides.

Treatment with a D-PDMP also boosted the activity of an enzyme
responsible for purging the body of fats by converting these fats into
bile, the fat-dissolving substance secreted by the liver.

In a final set of experiments, researchers compared the effects of
treatment with D-PDMP in two groups of healthy rabbits, both fed
high-fat diets, with half of them receiving treatment. Rabbits that ate
high-fat food alone developed all the classic signs of
atherosclerosis—fatty plaque buildup in the arteries and stiff, narrowed
blood vessels. Their cholesterol levels shot up 17-fold. By contrast,
rabbits treated with D-PDMP never developed atherosclerosis. Their
cholesterol levels also remained normal or near-normal.

The World Health Organizations estimates that high cholesterol claims
2.6 million lives worldwide each year. More than 70 million Americans
have high cholesterol, according to the U.S. Centers for Disease Control
and Prevention. Current cholesterol-lowering drugs, such as statins, do
not work in about one-third of people who take them, experts say.

Show Reference »

Fueling the Body on Fat - ScienceNewsline

Fueling the Body on Fat - ScienceNewsline

Published: January 4, 2011.
By Cell Press


Researchers have found what appears to be a critical tuning dial for
controlling whole body energy, according to a new report in the January
issue of Cell Metabolism, a Cell Press publication. When energy
levels within cells drop, it sets off a series of events designed to
increase the amount of calorie-rich dietary fat that the body will

This energy reset mechanism is surely critical for survival under
natural conditions of scarcity to ensure a steady supply of fuel, the
researchers say. Today, many of us who enjoy a Western diet loaded with
fat might do better if we could find a way to turn the activity of the
so-called AMPK-SRC-2 pathway down.

"Thousands of years ago, this would have been crucial," said Bert
O'Malley of Baylor College of Medicine. "Now it's trouble because we eat
so much fatty food."

Earlier studies had shown the enzyme AMPK to be an ancient energy
sensor. The enzyme causes cells to consume less energy in the form of
ATP and to produce more. AMPK also drives appetite.

The new work shows that AMPK also allows for the optimal absorption
of the most energy-rich fuel from the diet: fat. That effect of AMPK
depends on its activation of SRC-2, a master control gene whose job is
to switch other genes on.

When SRC-2 springs into action, it controls genes that lead to the
secretion of bile from the gall bladder into the intestine. "You need
bile to emulsify and absorb fat," O'Malley explained.

Mice lacking SRC-2 fail to absorb fat normally, they report. Those
deficiencies can be corrected by restoring bile acids to the gut.

Together with earlier work, the findings present a "pretty picture"
in which SRC-2 is involved in absorbing and storing fat. SRC-2 is also
known to play a role in releasing stored glucose from the liver. "It's
all about energy accretion, storage and delivery," O'Malley says.

This process takes place on a daily basis even when there is already
plenty of fat stored in the body. "It's designed to get in more fat," he
says. "Over evolutionary time, when you didn't know when the next meal
would be, you really couldn't get enough fat. Now, our next meal is at
the corner McDonald's."

The discovery reveals a key mechanism linking the cellular energy
state with the whole-body energy state and may ultimately have important
clinical implications, the researchers say.

"Obesity is all about fat absorption and storage," O'Malley said. "If
you could turn that down, you could have a major effect on a disease
that is slowly killing the population." He says his team is now
conducting studies in search of SRC-2 inhibitors that might do exactly


Why does the taste of liver and kidney make us almost vomit if its so healthy for us? - Paleohacks

Why does the taste of liver and kidney make us almost vomit if its so healthy for us? - Paleohacks

Well first of all, I don’t know any actual
authorities on nutrition that will extol the virtues of eating liver.
The liver's main function is to remove and store toxins from the blood.
And this toxic organ is supposed to be good for us? Another function
of the liver is to manufacture bile; bile has several functions and
effects. One of the effects is to contribute with billirubin in making
our feces brown and is partially responsible for the characteristic odor
of fecal matter. Which is why some people who have sensitive noses
find that liver and feces smell similar. SO between liver smelling like
feces, and being full of toxins, the argument seems to be that it is
full nutrients. If I was starving and it came between life and death I
would eat the disgusting thing to save my life. But there is nothing of
nutritional value in liver that is not readily available in more
healthy, safe, and most importantly delicious foods. So there it is.
Liver is unhealthy, tastes disgusting, and does not contain nutrients
unavailable in other food sources. Why are you forcing yourself to eat
liver again?

For some reason I am not able to comment on the comment.
Now when I said the liver removes and stores toxins from the blood, I
did not mean that the liver magically packages and removes the toxins
from the body, it stores the toxins. I thought that point was crystal
clear I hope it is now. I'd prefer to debate the facts and would
appreciate if you didn't use superstition, opinion, and fallacies as the
basis of your argument. That straw man you tried is bad form. Shame on
you. ARe you argiung to win or arguing to find truth? I prefer truth.
How about you?

Sorry, with the possible
exception of liver from a near-death animal there's no reason to expect
the liver to contain the very toxins it so capably packages and ships
out of the body. You could just as easily say that since the liver
removes toxins it must be full of anti-toxins.

"Now when I said the liver
removes and stores toxins from the blood, I did not mean that the liver
magically packages and removes the toxins from the body, it stores the
toxins. I thought that point was crystal clear I hope it is now."

is exactly where you have been misinformed. The liver is a storage
vehicle for some vitamins, and does produce some detoxifers that get
shipped around the body, but it itself is NOT a vehicle for toxin

Generally, fat stores are known to store toxins. Also,
actual filters such as the lungs, will "get dirty" from environmental


Every drop of vegetable oil takes us further along the path to Parkinson’s Disease | David Gillespie

Every drop of vegetable oil takes us further along the path to Parkinson’s Disease | David Gillespie

"The official position on the cause of Parkinson’s disease is that nobody has the slightest clue what causes the dopamine producing neurons to die"
The official position on the cause of Parkinson’s disease is that nobody has the slightest clue what causes the dopamine producing neurons to die. 
The only official risk factor is age.  But I think some dots need
joining and when that is done the culprit becomes very clear.

We know that a diet high in seed oils
causes the levels of Omega-6 fats in our cell membranes to rise
rapidly.  Those fats react quickly with oxygen and push the body into a
state of cascading cell damage called oxidative stress.   We also know that a major product of the oxidation of omega-6 fats is something with the charming name of 4-Hydroxynonenal (I’ll just use its street name of 4-HNE).  And we know that 4-HNE, whilst generally dangerous, is especially toxic to the neurons responsible for producing dopamine in our brain.

There, dots joined (it wasn’t that hard was it?).  Eating seed oils
(or anything which contains large amounts of omega-6 fats) induces the
production of a molecule which we know kills the neurons we depend upon
for dopamine production.  Kill enough of them and you have Parkinson’s

Thanks to the efforts of the processed food industry (aided and
abetted by the Heart Foundation), our diet is now completely saturated
with omega-6 fats.  Everything in a package uses it.  Every deep frier
uses it.  Every baker
uses it.  And every little bite of it is taking out the neurons you
depend on to keep you from the ravages of Parkinson’s disease.

Nothing I can say will restore the neurons you’ve already killed but I can stop you killing any more.

Don’t eat seed oils.


The Aetiology of Obesity Part 1 of 6: A New Hope

What is the underlying causes of our obesity epidemic? We explode
commonly held beliefs about obesity to come to some surprising
conclusions. Practical tips on weight management and good health.

"Insulin Resistance" with Dr. Robert Maki, ND

There is a growing body of research indicating that chronically elevated
levels of insulin, leading to insulin resistance is at the heart of
several chronic diseases afflicting our society: obesity, Type II
Diabetes, heart disease, high cholesterol, high blood pressure, fatty
liver (NAFLD), poly-cystic ovarian syndrome (PCOS), cancer, and even
Alzheimer's disease. It is important to understand these are not stand
alone conditions, but are all related to one dysfunctional metabolic
process. We will discuss the role elevated insulin has in the
development of these conditions and why a whole foods based diet is
critical to improving the dysfunction.

Dr. Robert Maki is a
Naturopathic Doctor and a graduate of Bastyr University in Seattle, WA.
Dr. Maki is also a faculty member at Hawthorn University and maintains a
private practice in Southern California, which is focused on
Bio-Identical Hormone Replacement Therapy (BHRT) and other hormonal
problems such as Diabetes, thyroid disorders and weight loss. In
addition to his private practice and role at Hawthorn, Dr. Maki is the
host of a healthy weight loss podcast on iTunes titled "The Dr. Rob


Homocysteine - Wikipedia,

Homocysteine - Wikipedia, the free encyclopedia

Homocysteine [IPA: ˌhəʊməʊˈsɪstiːn] is a non-protein α-amino acid. It is a homologue of the amino acid cysteine, differing by an additional methylene bridge (-CH2-). It is biosynthesized from methionine by the removal of its terminal Cε methyl group. Homocysteine can be recycled into methionine or converted into cysteine with the aid of B-vitamins.

While detection of high levels of homocysteine has been linked to
cardiovascular disease, lowering homocysteine levels may not improve

A high level of homocysteine makes a person more prone to endothelial
injury, which leads to vascular inflammation, which in turn may lead to
atherogenesis, which can result in ischemic injury.[2] Hyperhomocysteinemia is therefore a possible risk factor for coronary artery disease.
Coronary artery disease occurs when an atherosclerosis leads to
occlusion of the lumina of the coronary arteries. These arteries supply
the heart with oxygenated blood.

Hyperhomocysteinemia has been correlated with the occurrence of blood
clots, heart attacks and strokes, though it is unclear whether
hyperhomocysteinemia is an independent risk factor for these conditions.
It can cause miscarriage and/or pre-eclampsia in pregnant women, and
can lead to birth defects.[citation needed]