Exposure to Chemical Pollutants Increases Fat

http://www.scientificamerican.com/ar...tants-fat-diet

Study Finds Exposure to Chemical Pollutants Increases Fat
Rats exposed to high levels of chemical pollutants in fish oil could
not regulate fat properly
By Sara Goodman | January 15, 2010 | 8

FAT CHEMICAL: A chemical found in fatty foods could be sentencing
people to metabolic problems such as obesity and fatigue.

Researchers have for the first time found a connection between
exposure to certain chemicals and insulin resistance, according to a
study published in the online edition of Environmental Health
Perspectives.

A group of European scientists examined whether exposure to persistent
organic pollutants (POPs) contributed to insulin resistance, which has
been increasing around the world. More than 25 percent of U.S. adults
suffer from metabolic conditions stemming from insulin resistance that
include fatigue, obesity and difficulty regulating blood levels of fat
and sugar.

Researchers fed rats a high-fat diet of either crude or refined fish
oil from farmed Atlantic salmon over 28 days. The crude fish oil
contained average levels of POPs that people are exposed to through
fish consumption, while the refined oil contained none. Both had equal
fat levels.

They found that rats exposed to the crude fish oil developed belly fat
and could not regulate fat properly. They had higher levels of
cholesterol and several fatty acids in their livers. Those exposed to
the refined fish oil experienced none of those symptoms.

Researchers said the findings provide "compelling evidence" of a
causal relationship between POP exposure common in the food chain and
insulin resistance, and highlight the need to understand the
interactions of POPs and fat-containing foods such as fish, dairy
products and meat.

How to deal with POPs is particularly challenging because they persist
in the environment for long periods and can build up in animals'
tissues.

The 2001 Stockholm Convention, which the United States has ratified
but not signed, lists and bans numerous POPs from manufacture and use.
The researchers say their evidence reinforces the need to have
international agreements aimed at limiting the release of POPs into
the environment in an effort to protect public health.

Another instance where they should have had two other groups of rats,
both of which would be fed coconut oil rather than fish oil, one would
get the POPs and one would not. My guess is that they are not
familiar with the relevant literature, because it suggests that
coconut oil and POPs might not present any major problem, unlike fish
oil and POPs. If so, it would have been yet another good
demonstration of the apparent dangers of fish oil.

On Jul 9, 5:08*pm, montygraham wrote:
Another instance where they should have had two other groups of rats,
both of which would be fed coconut oil rather than fish oil, one would
get the POPs and one would not. *My guess is that they are not
familiar with the relevant literature, because it suggests that
coconut oil and POPs might not present any major problem, unlike fish
oil and POPs. *If so, it would have been yet another good
demonstration of the apparent dangers of fish oil.

Some POPs alter cells via a non-ROS mechanism. Some POPs produce
reactive quinones that bind DNA. POPs tend to hyperactive Phase I
enzymes which tend to produce more reactive chemicals so that they can
by bound and excreted by Phase II enzymes/anti-oxidants. Reducing
excess iron, proteins in addition to polyunsaturated oils should help
also.

In article
,
jay wrote:

On Jul 9, 5:08*pm, montygraham wrote:
Another instance where they should have had two other groups of rats,
both of which would be fed coconut oil rather than fish oil, one would
get the POPs and one would not. *My guess is that they are not
familiar with the relevant literature, because it suggests that
coconut oil and POPs might not present any major problem, unlike fish
oil and POPs. *If so, it would have been yet another good
demonstration of the apparent dangers of fish oil.

Some POPs alter cells via a non-ROS mechanism. Some POPs produce
reactive quinones that bind DNA. POPs tend to hyperactive Phase I
enzymes which tend to produce more reactive chemicals so that they can
by bound and excreted by Phase II enzymes/anti-oxidants. Reducing
excess iron, proteins in addition to polyunsaturated oils should help
also.

Do you have a citation for the above?
--
- Billy

Mad dog Republicans to the right. Democratic spider webs to the left. True conservatives, and liberals not to be found anywhere in the phantasmagoria
of the American political landscape.

America is not broke. The country is awash in wealth and cash.
It's just that it's not in your hands. It has been transferred, in the
greatest heist in history, from the workers and consumers to the banks
and the portfolios of the uber-rich.
http://www.politifact.com/wisconsin/.../michael-moore
/michael-moore-says-400-americans-have-more-wealth-/

... citation for the above?

Receptor- and reactive intermediate-mediated mechanisms of
teratogenesis.
Drugs and environmental chemicals can adversely alter the development
of the fetus at critical periods during pregnancy, resulting in death,
or in structural and functional birth defects in the surviving
offspring. This process of teratogenesis may not be evident until a
decade or more after birth. Postnatal functional abnormalities include
deficits in brain function, a variety of metabolic diseases, and
cancer. Due to the high degree of fetal cellular division and
differentiation, and to differences from the adult in many biochemical
pathways, the fetus is highly susceptible to teratogens, typically at
low exposure levels that do not harm the mother. Insights into the
mechanisms of teratogenesis come primarily from animal models and in
vitro systems, and involve either receptor-mediated or reactive
intermediate-mediated processes. Receptor-mediated mechanisms
involving the reversible binding of xenobiotic substrates to a
specific receptor are exemplified herein by the interaction of the
environmental chemical 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD or
"dioxin") with the cytosolic aryl hydrocarbon receptor (AHR), which
translocates to the nucleus and, in association with other proteins,
binds to AH-responsive elements (AHREs) in numerous genes, initiating
changes in gene transcription that can perturb development.
Alternatively, many xenobiotics are bioactivated by fetal enzymes like
the cytochromes P450 (CYPs) and prostaglandin H synthases (PHSs) to
highly unstable electrophilic or free radical reactive intermediates.
Electrophilic reactive intermediates can covalently (irreversibly)
bind to and alter the function of essential cellular macromolecules
(proteins, DNA), causing developmental anomalies. Free radical
reactive intermediates can enhance the formation of reactive oxygen
species (ROS), resulting in oxidative damage to cellular
macromolecules and/or altered signal transduction. The teratogenicity
of reactive intermediates is determined to a large extent by the
balance among embryonic and fetal pathways of xenobiotic
bioactivation, detoxification of the xenobiotic reactive intermediate,
detoxification of ROS, and repair of oxidative macromolecular damage.
PMID: 20020262

In article
,
jay wrote:

... citation for the above?

Receptor- and reactive intermediate-mediated mechanisms of
teratogenesis.
Drugs and environmental chemicals can adversely alter the development
of the fetus at critical periods during pregnancy, resulting in death,
or in structural and functional birth defects in the surviving
offspring. This process of teratogenesis may not be evident until a
decade or more after birth. Postnatal functional abnormalities include
deficits in brain function, a variety of metabolic diseases, and
cancer. Due to the high degree of fetal cellular division and
differentiation, and to differences from the adult in many biochemical
pathways, the fetus is highly susceptible to teratogens, typically at
low exposure levels that do not harm the mother. Insights into the
mechanisms of teratogenesis come primarily from animal models and in
vitro systems, and involve either receptor-mediated or reactive
intermediate-mediated processes. Receptor-mediated mechanisms
involving the reversible binding of xenobiotic substrates to a
specific receptor are exemplified herein by the interaction of the
environmental chemical 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD or
"dioxin") with the cytosolic aryl hydrocarbon receptor (AHR), which
translocates to the nucleus and, in association with other proteins,
binds to AH-responsive elements (AHREs) in numerous genes, initiating
changes in gene transcription that can perturb development.
Alternatively, many xenobiotics are bioactivated by fetal enzymes like
the cytochromes P450 (CYPs) and prostaglandin H synthases (PHSs) to
highly unstable electrophilic or free radical reactive intermediates.
Electrophilic reactive intermediates can covalently (irreversibly)
bind to and alter the function of essential cellular macromolecules
(proteins, DNA), causing developmental anomalies. Free radical
reactive intermediates can enhance the formation of reactive oxygen
species (ROS), resulting in oxidative damage to cellular
macromolecules and/or altered signal transduction. The teratogenicity
of reactive intermediates is determined to a large extent by the
balance among embryonic and fetal pathways of xenobiotic
bioactivation, detoxification of the xenobiotic reactive intermediate,
detoxification of ROS, and repair of oxidative macromolecular damage.
PMID: 20020262

Huh? That's all you got? ;O)
--
- Billy

Mad dog Republicans to the right. Democratic spider webs to the left. True conservatives, and liberals not to be found anywhere in the phantasmagoria
of the American political landscape.

America is not broke. The country is awash in wealth and cash.
It's just that it's not in your hands. It has been transferred, in the
greatest heist in history, from the workers and consumers to the banks
and the portfolios of the uber-rich.
http://www.politifact.com/wisconsin/.../michael-moore
/michael-moore-says-400-americans-have-more-wealth-/

citation for the above?

Dioxin: a review of its environmental effects and its aryl hydrocarbon
receptor biology.
A highly persistent trace environmental contaminant and one of the
most potent toxicants known is dioxin (2,3,7,8-tetrachlorodibenzo-para-
dioxin or TCDD). TCDD induces a broad spectrum of biological
responses, including induction of cytochrome P-450 1A1 (CYP1A1),
disruption of normal hormone signaling pathways, reproductive and
developmental defects, immunotoxicity, liver damage, wasting syndrome,
and cancer. Its classification was upgraded from "possible human
carcinogen" (group 2B) to "human carcinogen" (group 1) by the
International Agency for Research on Cancer (IARC) in 1997. Exposure
to TCDD may also cause changes in sex ratio, and tumor promotion in
other animals. Because of the growing public and scientific concern,
toxicological studies have been initiated to analyze the short- and
long-term effects of dioxin. TCDD brings about a wide variety of toxic
and biochemical effects via aryl hydrocarbon receptor (AhR)-mediated
signaling pathways. Essential steps in this adaptive mechanism include
AhR binding of ligand in the cytoplasm of cells associated with two
molecules of chaperone heatshock protein (Hsp90) and AhR interactive
protein, translocation of the receptor to the nucleus, dimerization
with the Ah receptor nuclear translocator, and binding of this
heterodimeric transcription factor (present in CYP1A) to dioxin-
responsive elements upstream of promoters that regulate the expression
of genes involved in xenobiotic metabolism. PMID: 15900503

... citation for the above?

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) alters the mRNA expression
of critical genes associated with cholesterol metabolism, bile acid
biosynthesis, and bile transport in rat liver: a microarray study.
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a potent hepatotoxin
that exerts its toxicity through binding to the aryl hydrocarbon
receptor (AhR) and the subsequent induction or repression of gene
transcription. In order to further identify novel genes and pathways
that may be associated with TCDD-induced hepatotoxicity, we
investigated gene changes in rat liver following exposure to single
oral doses of TCDD. Male Sprague-Dawley rats were administered single
doses of 0.4 microg/kg bw or 40 microg/kg bw TCDD and killed at 6 h,
24 h, or 7 days, for global analyses of gene expression. In general,
low-dose TCDD exposure resulted in greater than 2-fold induction of
genes coding for a battery of phase I and phase II metabolizing
enzymes including CYP1A1, CYP1A2, NADPH quinone oxidoreductase,
UGT1A6/7, and metallothionein 1. However, 0.4 microg/kg bw TCDD also
altered the expression of Gadd45a and Cyclin D1, suggesting that even
low-dose TCDD exposure can alter the expression of genes indicative of
cellular stress or DNA damage and associated with cell cycle control.
At the high-dose, widespread changes were observed for genes encoding
cellular signaling proteins, cellular adhesion, cytoskeletal and
membrane transport proteins as well as transcripts coding for lipid,
carbohydrate and nitrogen metabolism. In addition, decreased
expression of cytochrome P450 7A1, short heterodimer partner (SHP;
gene designation nr0b2), farnesyl X receptor (FXR), Ntcp, and Slc21a5
(oatp2) were observed and confirmed by RT-PCR analyses in independent
rat liver samples. Altered expression of these genes implies major
deregulation of cholesterol metabolism and bile acid synthesis and
transport. We suggest that these early and novel changes have the
potential to contribute significantly to TCDD induced hepatotoxicity
and hypercholesterolemia. PMID: 16054898

Do you have a citation for the above?

2,3,7,8-Tetrachlorodibenzo-p-dioxin induces apoptotic cell death and
cytochrome P4501A expression in developing Fundulus heteroclitus
embryos.
Fundulus heteroclitus embryos were exposed to 2,3,7,8-
tetrachlorodibenzo-p-dioxin (TCDD) during early development using
nanoinjection or water bath exposure. TCDD caused developmental
abnormalities that included hemorrhaging, loss of vascular integrity,
edema, stunted development and death. The LC(50) and LD(50) of TCDD
for Fundulus embryos were approximately 19.7+/-9.5 pg TCDD/microl
(water bath) and 0.25+/-0.09 ng TCDD/g embryo (nanoinjection). To
identify a possible cause for these developmental abnormalities we
analyzed the effects of TCDD on apoptotic cell death and cytochrome
P4501A (CYP1A) expression in the embryos. TCDD exposure increased
apoptotic cell death in several tissues including brain, eye, gill,
kidney, tail, intestine, heart, and vascular tissue. CYP1A expression
was also increased in the TCDD-exposed embryos predominantly in liver,
kidney, gill, heart, intestine, and in vascular tissues throughout the
embryo. There was co-occurrence of TCDD-induced apoptosis and CYP1A
expression in some, but not all, cell types. In addition the dose
response relationships for apoptosis and mortality were similar, while
CYP1A expression appeared more sensitive to TCDD induction. PMID:
11311389

... citation for the above?

Iron deficiency prevents liver toxicity of 2,3,7,8-tetrachlorodibenzo-
p-dioxin.
The compound 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) causes
hepatocellular damage and porphyria in C57B1/6J mice, among a wide
range of toxic effects. We compared the effect of TCDD toxicity in
iron-deficient mice with that in mice receiving a normal diet.
Porphyria did not develop in the iron-deficient animals, and these
animals were also protected from hepatocellular damage and certain
other toxic effects of TCDD. PMID: 432648