Re: The Molecular Mechanisms Underlying the Pro-Inflammatory Actions of Thiazolidinediones (TZDs) in Human Macrophages

MarilynMann wrote:
> The Molecular Mechanisms Underlying the Pro-Inflammatory Actions of
> Thiazolidinediones (TZDs) in Human Macrophages
>
> Julie M. Hall and Donald P. McDonnell*
>
> This version published online on May 8, 2007
> Molecular Endocrinology, doi:10.1210/me.2007-0060
>
> It is hypothesized that the anti-inflammatory actions of peroxisome
> proliferator-activated receptors (PPARs) may explain the protective
> effect of these receptors in diabetes, atherosclerosis, cancer and
> other inflammatory diseases. However, emerging evidence for pro-
> inflammatory activities of activated PPARs is concerning in light of
> new studies which associate PPAR modulators with an increased
> incidence of both cardiovascular events in humans and the sporadic
> formation of tumors in rodents. In an attempt to define the role of
> each PPAR subtype in inflammation, we made the unexpected observation
> that human PPAR is a positive regulator of inflammatory responses in
> both monocytes and macrophages. Notably, TNF -stimulated cells
> administered PPAR agonists express and secrete elevated levels of
> inflammatory cytokines. Most surprising, however, was the finding that
> thiazolidinediones (TZDs) and other known PPAR ligands display
> different degrees of pro-inflammatory activities in a PPAR - and PPAR -
> independent manner via their ability to augment PPAR signaling. A
> series of mechanistic studies revealed that TZDs, at clinically
> relevant concentrations, bind and activate the transcriptional
> activity of PPAR. Collectively, these studies suggest that the
> observed pro-inflammatory and potentially deleterious effects of PPAR
> ligands may be mediated through an off-target effect on PPAR. These
> studies highlight the need for PPAR modulators with increased receptor
> subtype-specificity. Furthermore, they suggest that differences in
> systemic exposure and consequently in the activation of PPAR and PPAR
> may explain why TZDs can exhibit both inflammatory and anti-
> inflammatory activities in humans.
>
> * * *
> In light of the controversy about Avandia, I thought some people might
> be interested in this.
>
> Marilyn

This underscores the importance of losing the visceral adipose tissue
(VAT) which is a major source of inflammatory cytokines even in the
absence of TZDs.

Vascular Endothelial Growth Factor Is Induced by the Inflammatory
Cytokines Interleukin-6 and Oncostatin M in Human Adipose Tissue In
Vitro and in Murine Adipose Tissue In Vivo.

Arterioscler Thromb Vasc Biol. 2007 May 24;

OBJECTIVE: It is believed that adipose tissue acts as an endocrine
organ by producing inflammatory mediators and thereby contributes to
the increased cardiovascular risk seen in obesity. A link between
adipose tissue mass and angiogenesis has been suggested. Vascular
endothelial growth factor (VEGF) seems to be implicated in this
process. Members of the glycoprotein (gp)130 ligand family regulate
VEGF expression in other cells. METHODS AND RESULTS: We used tissue
explants as well as primary cultures of preadipocytes and adipocytes
from human subcutaneous and visceral adipose tissue to investigate
whether the gp130 ligands oncostatin M (OSM), interleukin-6 (IL-6),
leukemia inhibitory factor (LIF), and cardiotrophin-1 (CT-1) regulate
VEGF expression in human adipose tissue. Human subcutaneous and
visceral adipose tissue responded to treatment with IL-6 and OSM with
a significant increase in VEGF production. Human preadipocytes were
isolated from subcutaneous and visceral adipose tissue. Adipocyte-
differentiation was induced by hormone-supplementation. All cell types
responded to IL-6 and OSM with a robust increase in VEGF protein
production and a similar increase in VEGF-specific mRNA. Furthermore,
IL-1beta synergistically enhanced the effect of OSM on VEGF
production. AG-490, a JAK/STAT inhibitor, abolished the OSM-dependent
VEGF induction almost completely. In mice, IL-6 and OSM increased
serum levels of VEGF and VEGF mRNA and vessel density in adipose
tissue. CONCLUSIONS: We speculate that the inflammatory cytokines IL-6
and OSM might support angiogenesis during adipose tissue growth by
upregulating VEGF.



May GOD bless you in HIS mighty way making you hungrier than ever.

Prayerfully in Jesus' awesome love,

Andrew <><
--
Andrew B. Chung, MD/PhD
http://ABChung.LiveJournal.com

"Unlike the 2PD-OMER Approach, weight loss diets can't be combined
with well-balanced diets"
http://HeartMDPhD.com/Love/TheTruth

On Jun 15, 10:43 am, "Andrew B. Chung, MD/PhD" <l...@thetruth.com>
wrote:
> MarilynMann wrote:
> > The Molecular Mechanisms Underlying the Pro-Inflammatory Actions of
> > Thiazolidinediones (TZDs) in Human Macrophages
>
> > Julie M. Hall and Donald P. McDonnell*
>
> > This version published online on May 8, 2007
> > Molecular Endocrinology, doi:10.1210/me.2007-0060
>
> > It is hypothesized that the anti-inflammatory actions of peroxisome
> > proliferator-activated receptors (PPARs) may explain the protective
> > effect of these receptors in diabetes, atherosclerosis, cancer and
> > other inflammatory diseases. However, emerging evidence for pro-
> > inflammatory activities of activated PPARs is concerning in light of
> > new studies which associate PPAR modulators with an increased
> > incidence of both cardiovascular events in humans and the sporadic
> > formation of tumors in rodents. In an attempt to define the role of
> > each PPAR subtype in inflammation, we made the unexpected observation
> > that human PPAR is a positive regulator of inflammatory responses in
> > both monocytes and macrophages. Notably, TNF -stimulated cells
> > administered PPAR agonists express and secrete elevated levels of
> > inflammatory cytokines. Most surprising, however, was the finding that
> > thiazolidinediones (TZDs) and other known PPAR ligands display
> > different degrees of pro-inflammatory activities in a PPAR - and PPAR -
> > independent manner via their ability to augment PPAR signaling. A
> > series of mechanistic studies revealed that TZDs, at clinically
> > relevant concentrations, bind and activate the transcriptional
> > activity of PPAR. Collectively, these studies suggest that the
> > observed pro-inflammatory and potentially deleterious effects of PPAR
> > ligands may be mediated through an off-target effect on PPAR. These
> > studies highlight the need for PPAR modulators with increased receptor
> > subtype-specificity. Furthermore, they suggest that differences in
> > systemic exposure and consequently in the activation of PPAR and PPAR
> > may explain why TZDs can exhibit both inflammatory and anti-
> > inflammatory activities in humans.
>
> > * * *
> > In light of the controversy about Avandia, I thought some people might
> > be interested in this.
>
> > Marilyn
>
> This underscores the importance of losing the visceral adipose tissue
> (VAT) which is a major source of inflammatory cytokines even in the
> absence of TZDs.
>
> Vascular Endothelial Growth Factor Is Induced by the Inflammatory
> Cytokines Interleukin-6 and Oncostatin M in Human Adipose Tissue In
> Vitro and in Murine Adipose Tissue In Vivo.
>
> Arterioscler Thromb Vasc Biol. 2007 May 24;
>
> OBJECTIVE: It is believed that adipose tissue acts as an endocrine
> organ by producing inflammatory mediators and thereby contributes to
> the increased cardiovascular risk seen in obesity. A link between
> adipose tissue mass and angiogenesis has been suggested. Vascular
> endothelial growth factor (VEGF) seems to be implicated in this
> process. Members of the glycoprotein (gp)130 ligand family regulate
> VEGF expression in other cells. METHODS AND RESULTS: We used tissue
> explants as well as primary cultures of preadipocytes and adipocytes
> from human subcutaneous and visceral adipose tissue to investigate
> whether the gp130 ligands oncostatin M (OSM), interleukin-6 (IL-6),
> leukemia inhibitory factor (LIF), and cardiotrophin-1 (CT-1) regulate
> VEGF expression in human adipose tissue. Human subcutaneous and
> visceral adipose tissue responded to treatment with IL-6 and OSM with
> a significant increase in VEGF production. Human preadipocytes were
> isolated from subcutaneous and visceral adipose tissue. Adipocyte-
> differentiation was induced by hormone-supplementation. All cell types
> responded to IL-6 and OSM with a robust increase in VEGF protein
> production and a similar increase in VEGF-specific mRNA. Furthermore,
> IL-1beta synergistically enhanced the effect of OSM on VEGF
> production. AG-490, a JAK/STAT inhibitor, abolished the OSM-dependent
> VEGF induction almost completely. In mice, IL-6 and OSM increased
> serum levels of VEGF and VEGF mRNA and vessel density in adipose
> tissue. CONCLUSIONS: We speculate that the inflammatory cytokines IL-6
> and OSM might support angiogenesis during adipose tissue growth by
> upregulating VEGF.
>
> May GOD bless you in HIS mighty way making you hungrier than ever.
>
> Prayerfully in Jesus' awesome love,
>
> Andrew <><
> --
> Andrew B. Chung, MD/PhDhttp://ABChung.LiveJournal.com
>
> "Unlike the 2PD-OMER Approach, weight loss diets can't be combined
> with well-balanced diets"http://HeartMDPhD.com/Love/TheTruth

Since you seem to believe in Jesus so much, in His name, why don't
you take a few minutes to translate your incomprehensible gobble-de-
gook
into something that non-medical people could actually understand? For
example, instead of the pretentious "Visceral Adipose Tissue", why
don't
you just simply say "belly fat"? People who hide behind big words are
generally
trying to mask either the unimportant ideas, or that they are trying
to lie to
your face.

Jesus spoke plainly; you speak like a pretentious blowhard. Which is
why
I tend to ignore most of your posts.

neighbor kevinbertsch...@yahoo.ca wrote:
> Andrew, in the Holy Spirit, boldly wrote:
> > neighbor MarilynMann wrote:
>
> > > The Molecular Mechanisms Underlying the Pro-Inflammatory Actions of
> > > Thiazolidinediones (TZDs) in Human Macrophages
> >
> > > Julie M. Hall and Donald P. McDonnell*
> >
> > > This version published online on May 8, 2007
> > > Molecular Endocrinology, doi:10.1210/me.2007-0060
> >
> > > It is hypothesized that the anti-inflammatory actions of peroxisome
> > > proliferator-activated receptors (PPARs) may explain the protective
> > > effect of these receptors in diabetes, atherosclerosis, cancer and
> > > other inflammatory diseases. However, emerging evidence for pro-
> > > inflammatory activities of activated PPARs is concerning in light of
> > > new studies which associate PPAR modulators with an increased
> > > incidence of both cardiovascular events in humans and the sporadic
> > > formation of tumors in rodents. In an attempt to define the role of
> > > each PPAR subtype in inflammation, we made the unexpected observation
> > > that human PPAR is a positive regulator of inflammatory responses in
> > > both monocytes and macrophages. Notably, TNF -stimulated cells
> > > administered PPAR agonists express and secrete elevated levels of
> > > inflammatory cytokines. Most surprising, however, was the finding that
> > > thiazolidinediones (TZDs) and other known PPAR ligands display
> > > different degrees of pro-inflammatory activities in a PPAR - and PPAR -
> > > independent manner via their ability to augment PPAR signaling. A
> > > series of mechanistic studies revealed that TZDs, at clinically
> > > relevant concentrations, bind and activate the transcriptional
> > > activity of PPAR. Collectively, these studies suggest that the
> > > observed pro-inflammatory and potentially deleterious effects of PPAR
> > > ligands may be mediated through an off-target effect on PPAR. These
> > > studies highlight the need for PPAR modulators with increased receptor
> > > subtype-specificity. Furthermore, they suggest that differences in
> > > systemic exposure and consequently in the activation of PPAR and PPAR
> > > may explain why TZDs can exhibit both inflammatory and anti-
> > > inflammatory activities in humans.
> >
> > > * * *
> > > In light of the controversy about Avandia, I thought some people might
> > > be interested in this.
> >
> > > Marilyn
> >
> > This underscores the importance of losing the visceral adipose tissue
> > (VAT) which is a major source of inflammatory cytokines even in the
> > absence of TZDs.
> >
> > Vascular Endothelial Growth Factor Is Induced by the Inflammatory
> > Cytokines Interleukin-6 and Oncostatin M in Human Adipose Tissue In
> > Vitro and in Murine Adipose Tissue In Vivo.
> >
> > Arterioscler Thromb Vasc Biol. 2007 May 24;
> >
> > OBJECTIVE: It is believed that adipose tissue acts as an endocrine
> > organ by producing inflammatory mediators and thereby contributes to
> > the increased cardiovascular risk seen in obesity. A link between
> > adipose tissue mass and angiogenesis has been suggested. Vascular
> > endothelial growth factor (VEGF) seems to be implicated in this
> > process. Members of the glycoprotein (gp)130 ligand family regulate
> > VEGF expression in other cells. METHODS AND RESULTS: We used tissue
> > explants as well as primary cultures of preadipocytes and adipocytes
> > from human subcutaneous and visceral adipose tissue to investigate
> > whether the gp130 ligands oncostatin M (OSM), interleukin-6 (IL-6),
> > leukemia inhibitory factor (LIF), and cardiotrophin-1 (CT-1) regulate
> > VEGF expression in human adipose tissue. Human subcutaneous and
> > visceral adipose tissue responded to treatment with IL-6 and OSM with
> > a significant increase in VEGF production. Human preadipocytes were
> > isolated from subcutaneous and visceral adipose tissue. Adipocyte-
> > differentiation was induced by hormone-supplementation. All cell types
> > responded to IL-6 and OSM with a robust increase in VEGF protein
> > production and a similar increase in VEGF-specific mRNA. Furthermore,
> > IL-1beta synergistically enhanced the effect of OSM on VEGF
> > production. AG-490, a JAK/STAT inhibitor, abolished the OSM-dependent
> > VEGF induction almost completely. In mice, IL-6 and OSM increased
> > serum levels of VEGF and VEGF mRNA and vessel density in adipose
> > tissue. CONCLUSIONS: We speculate that the inflammatory cytokines IL-6
> > and OSM might support angiogenesis during adipose tissue growth by
> > upregulating VEGF.
> >
> > May GOD bless you in HIS mighty way making you hungrier than ever.
>
> Since you seem to believe in Jesus so much, in His name, why don't
> you take a few minutes to translate your incomprehensible gobble-de-
> gook
> into something that non-medical people could actually understand?

It would take several hours to translate the content in these
abstracts into something that non-medical people can unequivocably
understand.

> For example, instead of the pretentious "Visceral Adipose Tissue", why
> don't
> you just simply say "belly fat"?

Because it would not be accurate.

> People who hide behind big words are
> generally
> trying to mask either the unimportant ideas, or that they are trying
> to lie to
> your face.

VAT is not a big word and it does sound like FAT.

> Jesus spoke plainly; you speak like a pretentious blowhard.

Actually, I have not been speaking here.

> Which is why I tend to ignore most of your posts.

You have the free will that GOD has elected to generously give all
souls per HIS infinite and perfect free will.

The brethren of LORD Jesus Christ are neither perfect nor more
special...

.... we are simply forgiven by GOD:

http://www.interviewwithgod.com/forgiven/

May you wisely choose to do be forgiven too by publicly declaring with
your mouth that "Jesus is LORD:"

http://HeartMDPhD.com/HolySpirit/TheWay

Prayerfully in Jesus' awesome love,

Andrew <><
--
Andrew B. Chung, MD/PhD
http://ABChung.LiveJournal.com

"Unlike the 2PD-OMER Approach, weight loss diets can't be combined
with well-balanced diets."
http://HeartMDPhD.com/Love/TheTruth

On Jun 16, 10:05 am, "Andrew B. Chung, MD/PhD" <l...@thetruth.com>
wrote:
> neighbor kevinbertsch...@yahoo.ca wrote:
> > Andrew, in the Holy Spirit, boldly wrote:
> > > neighbor MarilynMann wrote:
>
> > > > The Molecular Mechanisms Underlying the Pro-Inflammatory Actions of
> > > > Thiazolidinediones (TZDs) in Human Macrophages
>
> > > > Julie M. Hall and Donald P. McDonnell*
>
> > > > This version published online on May 8, 2007
> > > > Molecular Endocrinology, doi:10.1210/me.2007-0060
>
> > > > It is hypothesized that the anti-inflammatory actions of peroxisome
> > > > proliferator-activated receptors (PPARs) may explain the protective
> > > > effect of these receptors in diabetes, atherosclerosis, cancer and
> > > > other inflammatory diseases. However, emerging evidence for pro-
> > > > inflammatory activities of activated PPARs is concerning in light of
> > > > new studies which associate PPAR modulators with an increased
> > > > incidence of both cardiovascular events in humans and the sporadic
> > > > formation of tumors in rodents. In an attempt to define the role of
> > > > each PPAR subtype in inflammation, we made the unexpected observation
> > > > that human PPAR is a positive regulator of inflammatory responses in
> > > > both monocytes and macrophages. Notably, TNF -stimulated cells
> > > > administered PPAR agonists express and secrete elevated levels of
> > > > inflammatory cytokines. Most surprising, however, was the finding that
> > > > thiazolidinediones (TZDs) and other known PPAR ligands display
> > > > different degrees of pro-inflammatory activities in a PPAR - and PPAR -
> > > > independent manner via their ability to augment PPAR signaling. A
> > > > series of mechanistic studies revealed that TZDs, at clinically
> > > > relevant concentrations, bind and activate the transcriptional
> > > > activity of PPAR. Collectively, these studies suggest that the
> > > > observed pro-inflammatory and potentially deleterious effects of PPAR
> > > > ligands may be mediated through an off-target effect on PPAR. These
> > > > studies highlight the need for PPAR modulators with increased receptor
> > > > subtype-specificity. Furthermore, they suggest that differences in
> > > > systemic exposure and consequently in the activation of PPAR and PPAR
> > > > may explain why TZDs can exhibit both inflammatory and anti-
> > > > inflammatory activities in humans.
>
> > > > * * *
> > > > In light of the controversy about Avandia, I thought some people might
> > > > be interested in this.
>
> > > > Marilyn
>
> > > This underscores the importance of losing the visceral adipose tissue
> > > (VAT) which is a major source of inflammatory cytokines even in the
> > > absence of TZDs.
>
> > > Vascular Endothelial Growth Factor Is Induced by the Inflammatory
> > > Cytokines Interleukin-6 and Oncostatin M in Human Adipose Tissue In
> > > Vitro and in Murine Adipose Tissue In Vivo.
>
> > > Arterioscler Thromb Vasc Biol. 2007 May 24;
>
> > > OBJECTIVE: It is believed that adipose tissue acts as an endocrine
> > > organ by producing inflammatory mediators and thereby contributes to
> > > the increased cardiovascular risk seen in obesity. A link between
> > > adipose tissue mass and angiogenesis has been suggested. Vascular
> > > endothelial growth factor (VEGF) seems to be implicated in this
> > > process. Members of the glycoprotein (gp)130 ligand family regulate
> > > VEGF expression in other cells. METHODS AND RESULTS: We used tissue
> > > explants as well as primary cultures of preadipocytes and adipocytes
> > > from human subcutaneous and visceral adipose tissue to investigate
> > > whether the gp130 ligands oncostatin M (OSM), interleukin-6 (IL-6),
> > > leukemia inhibitory factor (LIF), and cardiotrophin-1 (CT-1) regulate
> > > VEGF expression in human adipose tissue. Human subcutaneous and
> > > visceral adipose tissue responded to treatment with IL-6 and OSM with
> > > a significant increase in VEGF production. Human preadipocytes were
> > > isolated from subcutaneous and visceral adipose tissue. Adipocyte-
> > > differentiation was induced by hormone-supplementation. All cell types
> > > responded to IL-6 and OSM with a robust increase in VEGF protein
> > > production and a similar increase in VEGF-specific mRNA. Furthermore,
> > > IL-1beta synergistically enhanced the effect of OSM on VEGF
> > > production. AG-490, a JAK/STAT inhibitor, abolished the OSM-dependent
> > > VEGF induction almost completely. In mice, IL-6 and OSM increased
> > > serum levels of VEGF and VEGF mRNA and vessel density in adipose
> > > tissue. CONCLUSIONS: We speculate that the inflammatory cytokines IL-6
> > > and OSM might support angiogenesis during adipose tissue growth by
> > > upregulating VEGF.
>
> > > May GOD bless you in HIS mighty way making you hungrier than ever.
>
> > Since you seem to believe in Jesus so much, in His name, why don't
> > you take a few minutes to translate your incomprehensible gobble-de-
> > gook
> > into something that non-medical people could actually understand?
>
> It would take several hours to translate the content in these
> abstracts into something that non-medical people can unequivocably
> understand.
>
> > For example, instead of the pretentious "Visceral Adipose Tissue", why
> > don't
> > you just simply say "belly fat"?
>
> Because it would not be accurate.
>
> > People who hide behind big words are
> > generally
> > trying to mask either the unimportant ideas, or that they are trying
> > to lie to
> > your face.
>
> VAT is not a big word and it does sound like FAT.
>
> > Jesus spoke plainly; you speak like a pretentious blowhard.
>
> Actually, I have not been speaking here.
>

No, just typing, like a 12 year old kid who has been caught stealing
dad's beer from the fridge.