Celexa Weight Gain
Celexa has been a popular antidepressant for several decades and Celexa weight
gain has been overlooked by the healthcare industry. It is normal for 55% of those
taking Celexa to experience weight gain. Unfortunately, 40.6 percent of the people
taking Celexa will gain 7% or more weight, the health concerns are real. (1)
Further studies are listed below but The Harper Method has one interest; helping
those that have Celexa weight gain and losing the weight safely.
Who is this method for?
It is for those who may or may not want to stay on Celexa
It is also for those that are now off Celexa
It is for those that have gained weight due to Celexa
It is for those that have tried to diet and exercise and the Celexa weight gain will
not come off
Some of the reasons for Celexa weight gain found on the Internet are absurd at
best.
Examples:
"Celexa has been associated with slight weight gain, but it’s thought that the drug
itself doesn’t cause this effect. Rather, the weight increase is likely due to
improved appetite from taking the drug. A better appetite can cause you to eat
more, leading to increased body weight." Source
"Monitor your diet and get exercise" Source
The list goes on and on. If diet and exercise worked for Celexa weight gain you
would not be doing a Google search for answers to the Celexa weight gain.
Dr. Tracey Marks, M.D. provides a YouTube video detailing how histamine
receptor H1 can be the cause of antidepressant induced weight gain. Click here to
view. The Dr. would have been well served to continue her research. The Harper
Method is based upon the over activation of the JNK gene. Histamine as well as
other substances make this JNK gene become to active. Antidepressants cause the
JNK gene to become over active and is the direct source of the antidepressant
weight gain.
Reduce the activation of the JNK gene and histamine H1 receptor is a mute point.
If humans did not have the JNK gene there is no possible way for a human to
become overweight.
How this method works
You need to start reducing the activation of the JNK gene as a first step. The JNK
gene is associated with weight gain and all antidepressants induce the activation of
the JNK gene. Until you do this; all of the exercise and dieting in the world will be
of no use. You likely know this already.
How this is done is simple. After 22 years of research two supplements have been
formulated in reduce the activation of the JNK1, JNK 2 and to slightly reduce the
activation of the JNK 3. Additionally, other proteins that reside upstream of the
JNK's need to be silenced and these are silenced with the supplements as well.
Foods; you should start eliminating foods with preservatives as your first diet
change.
Exercise; if you do not get any exercise, it is time to start with walking. At least 3
walks a week, with each walk for 20 minutes.
The two supplements setup your body to lose the weight gain caused by Celexa but
you also need to do the normal things that help you lose weight; diet and exercise.
I am assuming you have already tried diet and exercise to combat the Celexa
weight gain, without Celexa weight loss success.
After 22 years of research there is now a simple solution. Two supplements have
been formulated to decrease the activation of the JNK gene and provide you, for
the first time, the chance to lose the Celexa weight gain. They are called JNK 5 and
Optimum Solace. The JNK 5 provides the nutrients to reduce the activation of the
JNK gene and also the proteins that reside upstream of the JNK that continue to
activate this gene.
The Optimum Solace also reduces the JNK activation and the saffron in the
supplement help bring you a relaxed calm feeling. Without making you tired.
These two supplements are also sold at a massively reduced price so the majority
can afford their benefits. It is time to take control back and be the you, you want to
be.
(1) Jan-Feb 2015;37(1):46-8.
doi: 10.1016/j.genhosppsych.2014.10.011. Epub 2014 Oct 31.
Weight gain and associated factors in patients using newer antidepressant drugs
Objective: The aim of the present study was to examine weight gain and its
association with clinical and sociodemographic characteristics in patients using
newer antidepressants.
Methods: The study had a cross-sectional design. A total of 362 consecutive
psychiatric patients taking antidepressant drugs for 6 to 36 months were included
in the study.
Results: The prevalence rate of weight gain was 55.2%; 40.6% of the patients had
a weight gain of 7% or more compared to the baseline. Overall, antidepressant use
was significantly related to increased body weight. Specifically, citalopram,
escitalopram, sertraline, paroxetine, venlafaxine, duloxetine and mirtazapine, but
not fluoxetine, were associated with significant weight gain. Multivariate logistic
regression analysis indicated that lower education status, lower body mass index at
the onset of antidepressant use and family history of obesity were independent
predictors of weight gain ≥7% compared to the baseline.
Conclusions: The study results suggest that patients who take newer
antidepressants might have significant problems related to body weight.
Keywords: Antidepressants; Body mass index; Weight gain.
(2) JNK at the crossroad of obesity, insulin resistance, and cell stress response
Background: The cJun-N-terminal-kinase (JNK) plays a central role in the cell
stress response, with outcomes ranging from cell death to cell proliferation and
survival, depending on the specific context. JNK is also one of the most
investigated signal transducers in obesity and insulin resistance, and studies have
identified new molecular mechanisms linking obesity and insulin resistance.
Emerging evidence indicates that whereas JNK1 and JNK2 isoforms promote the
development of obesity and insulin resistance, JNK3 activity protects from
excessive adiposity. Furthermore, current evidence indicates that JNK activity
within specific cell types may, in specific stages of disease progression, promote
cell tolerance to the stress associated with obesity and type-2 diabetes.
Scope of review: This review provides an overview of the current literature on the
role of JNK in the progression from obesity to insulin resistance, NAFLD, type-2
diabetes, and diabetes complications.
Major conclusion: Whereas current evidence indicates that JNK1/2 inhibition may
improve insulin sensitivity in obesity, the role of JNK in the progression from
insulin resistance to diabetes, and its complications is largely unresolved. A better
understanding of the role of JNK in the stress response to obesity and type-2
diabetes, and the development of isoform-specific inhibitors with specific tissue
distribution will be necessary to exploit JNK as possible drug target for the
treatment of type-2 diabetes.
Keywords: Autophagy; Diabetes; Endoplasmic eeticulum stress; Inflammation;
MAPK; Oxidative stress.
(3) Role of c-Jun N-terminal Kinase (JNK) in Obesity and Type 2 Diabetes
Obesity has been described as a global epidemic and is a low-grade chronic
inflammatory disease that arises as a consequence of energy imbalance. Obesity
increases the risk of type 2 diabetes (T2D), by mechanisms that are not entirely
clarified. Elevated circulating pro-inflammatory cytokines and free fatty acids
(FFA) during obesity cause insulin resistance and ß-cell dysfunction, the two main
features of T2D, which are both aggravated with the progressive development of
hyperglycemia. The inflammatory kinase c-jun N-terminal kinase (JNK) responds
to various cellular stress signals activated by cytokines, free fatty acids and
hyperglycemia, and is a key mediator in the transition between obesity and T2D.
Specifically, JNK mediates both insulin resistance and ß-cell dysfunction, and is
therefore a potential target for T2D therapy.
Keywords: JNK; c-Jun N-terminal kinase; glucotoxicity; inflammation; insulin
resistance; lipotoxicity; obesity; type 2 diabetes.
(4) Adipocyte-Macrophage Cross-Talk in Obesity
Obesity is characterized by the chronic low-grade activation of the innate immune
system. In this respect, macrophage-elicited metabolic inflammation and
adipocyte-macrophage interaction has a primary importance in obesity. Large
amounts of macrophages are accumulated by different mechanisms in obese
adipose tissue. Hypertrophic adipocyte-derived chemotactic monocyte
chemoattractant protein-1 (MCP-1)/C-C chemokine receptor 2 (CCR2) pathway
also promotes more macrophage accumulation into the obese adipose tissue.
However, increased local extracellular lipid concentrations is a final mechanism
for adipose tissue macrophage accumulation. A paracrine loop involving free fatty
acids and tumor necrosis factor-alpha (TNF-alpha) between adipocytes and
macrophages establishes a vicious cycle that aggravates inflammatory changes in
the adipose tissue. Adipocyte-specific caspase-1 and production of interleukin-
1beta (IL-1beta) by macrophages; both adipocyte and macrophage induction by
toll like receptor-4 (TLR4) through nuclear factor-kappaB (NF-kappaB) activation;
free fatty acid-induced and TLR-mediated activation of c-Jun N-terminal kinase
(JNK)-related pro-inflammatory pathways in CD11c+ immune cells; are effective
in macrophage accumulation and in the development of adipose tissue
inflammation. Old adipocytes are removed by macrophages through trogocytosis
or sending an "eat me" signal. The obesity-induced changes in adipose tissue
macrophage numbers are mainly due to increases in the triple-positive CD11b+
F4/80+ CD11c+ adipose tissue macrophage subpopulation. The ratio of M1-to-M2
macrophages is increased in obesity. Furthermore, hypoxia along with higher
concentrations of free fatty acids exacerbates macrophage-mediated inflammation
in obesity. The metabolic status of adipocytes is a major determinant of
macrophage inflammatory output. Macrophage/adipocyte fatty-acid-binding
proteins act at the interface of metabolic and inflammatory pathways. Both
macrophages and adipocytes are the sites for active lipid metabolism and signaling.
Keywords: C-C chemokine receptor 2 (CCR2); Chemokine (C-C motif) ligand 2
(CCL2); Free fatty acids; Hypoxia-inducible factor-1 alpha (HIF-1alpha); Insulin-
like growth factor-1 (IGF1); Interleukin-6 (IL-6); M1 macrophages; M2
macrophages; Monocyte chemoattractant protein-1 (MCP-1); NOD-like receptor
(NLR) family protein (NLRP3); Obesity; Toll like receptor 4 (TLR4); Tumor
necrosis factor-alpha (TNF-alpha); Visceral adipose tissue.
(5) The Role of JNk Signaling Pathway in Obesity-Driven Insulin Resistance
Obesity is not only closely related to insulin resistance but is one of the main
factors leading to the formation of Type 2 Diabetes (T2D) too. The c-Jun N-
terminal kinase (JNK) family is a member of the mitogen-activated protein kinase
(MAPK) superfamily. JNK is also one of the most investigated signal transducers
in obesity and insulin resistance. JNK-centric JNK signaling pathway can be
activated by growth factors, cytokines, stress responses, and other factors. Many
researches have identified that the activated phosphorylation JNK negatively
regulates insulin signaling pathway in insulin resistance which can be
simultaneously regulated by multiple signaling pathways related to the JNK
signaling pathway. In this review, we provide an overview of the composition of
the JNK signaling pathway, its regulation of insulin signaling pathway, and the
relationship between the JNK signaling pathway and other pathways in insulin
resistance.
Keywords: JNK signaling pathway; insulin resistance; obesity; type 2 diabetes.
(6) JNK expression by macrophages promotes obesity-induced insulin resistance
and inflammation
The cJun NH(2)-terminal kinase (JNK) signaling pathway contributes to
inflammation and plays a key role in the metabolic response to obesity, including
insulin resistance. Macrophages are implicated in this process. To test the role of
JNK, we established mice with selective JNK deficiency in macrophages. We
report that feeding a high-fat diet to control and JNK-deficient mice caused similar
obesity, but only mice with JNK-deficient macrophages remained insulin-sensitive.
The protection of mice with macrophage-specific JNK deficiency against insulin
resistance was associated with reduced tissue infiltration by macrophages.
Immunophenotyping demonstrated that JNK was required for pro-inflammatory
macrophage polarization. These studies demonstrate that JNK in macrophages is
required for the establishment of obesity-induced insulin resistance and
inflammation.
(7) The Pathogenesis of Obesity-Associated Adipose Tissue Inflammation
Obesity is characterized by a state of chronic, low-grade inflammation. However,
excessive fatty acid release may worsen adipose tissue inflammation and
contributes to insulin resistance. In this case, several novel and highly active
molecules are released abundantly by adipocytes like leptin, resistin, adiponectin
or visfatin, as well as some more classical cytokines. Most likely cytokines that are
released by inflammatory cells infiltrating obese adipose tissue are such as tumor
necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6), monocyte chemoattractant
protein 1 (MCP-1) (CCL-2) and IL-1. All of those molecules may act on immune
cells leading to local and generalized inflammation. In this process, toll-like
receptor 4 (TLR4)/phosphatidylinositol-3'-kinase (PI3K)/Protein kinase B (Akt)
signaling pathway, the unfolded protein response (UPR) due to endoplasmic
reticulum (ER) stress through hyperactivation of c-Jun N-terminal Kinase (JNK) -
Activator Protein 1 (AP1) and inhibitor of nuclear factor kappa-B kinase beta
(IKKbeta)-nuclear factor kappa B (NF-kappaB) pathways play an important role,
and may also affect vascular endothelial function by modulating vascular nitric
oxide and superoxide release. Additionally, systemic oxidative stress, macrophage
recruitment, increase in the expression of NOD-like receptor (NLR) family protein
(NLRP3) inflammasone and adipocyte death are predominant determinants in the
pathogenesis of obesity-associated adipose tissue inflammation. In this chapter
potential involvement of these factors that contribute to the adverse effects of
obesity are reviewed.
Keywords: Adipose tissue macrophages (ATMs); Autophagy; Ceramide;
Endoplasmic reticulum stress; Inducible nitric oxide synthase (iNOS);
Lipotoxicity; M1 adipose tissue macrophages; Macrophage migration inhibitory
factor (MIF); Monocyte chemoattractant protein 1 (MCP-1); Nuclear factor kappa
B (NF-kappaB); Obesity; Reactive oxygen species (ROS); Saturated fatty acid;
Toll-like receptor 4 (TLR4); Tumor necrosis factor alpha (TNF-alpha); Vascular
endothelial growth factor (VEGF).
Celexa Weight Gain
Celexa has been a popular
antidepressant for several decades and
Celexa weight gain has been
overlooked by the healthcare industry.
It is normal for 55% of those taking
Celexa to experience weight gain.
Unfortunately, 40.6 percent of the
people taking Celexa will gain 7% or
more weight, the health concerns are
real. (1)
Further studies are listed below but
The Harper Method has one interest;
helping those that have Celexa weight
gain and losing the weight safely.
Who is this method for?
It is for those who may or may not
want to stay on Celexa
It is also for those that are now off
Celexa
It is for those that have gained weight
due to Celexa
It is for those that have tried to diet
and exercise and the Celexa weight
gain will not come off
Some of the reasons for Celexa
weight gain found on the Internet are
absurd at best. Examples:
"Celexa has been associated with
slight weight gain, but it’s thought
that the drug itself doesn’t cause this
effect. Rather, the weight increase is
likely due to improved appetite from
taking the drug. A better appetite
can cause you to eat more, leading
to increased body weight." Source
"Monitor your diet and get exercise"
Source
The list goes on and on. If diet and
exercise worked for Celexa weight
gain you would not be doing a Google
search for answers to the Celexa
weight gain.
Dr. Tracey Marks, M.D. provides a
YouTube video detailing how
histamine receptor H1 can be the
cause of antidepressant induced
weight gain. Click here to view. The
Dr. would have been well served to
continue her research. The Harper
Method is based upon the over
activation of the JNK gene. Histamine
as well as other substances make this
JNK gene become to active.
Antidepressants cause the JNK gene
to become over active and is the direct
source of the antidepressant weight
gain.
Reduce the activation of the JNK
gene and histamine H1 receptor is a
mute point.
If humans did not have the JNK gene
there is no possible way for a human
to become overweight.
How this method works
You need to start reducing the
activation of the JNK gene as a first
step. The JNK gene is associated with
weight gain and all antidepressants
induce the activation of the JNK gene.
Until you do this; all of the exercise
and dieting in the world will be of no
use. You likely know this already.
How this is done is simple. After 22
years of research two supplements
have been formulated in reduce the
activation of the JNK1, JNK 2 and to
slightly reduce the activation of the
JNK 3. Additionally, other proteins
that reside upstream of the JNK's need
to be silenced and these are silenced
with the supplements as well.
Foods; you should start eliminating
foods with preservatives as your first
diet change.
Exercise; if you do not get any
exercise, it is time to start with
walking. At least 3 walks a week,
with each walk for 20 minutes.
The two supplements setup your body
to lose the weight gain caused by
Celexa but you also need to do the
normal things that help you lose
weight; diet and exercise.
I am assuming you have already tried
diet and exercise to combat the
Celexa weight gain, without Celexa
weight loss success.
After 22 years of research there is
now a simple solution. Two
supplements have been formulated to
decrease the activation of the JNK
gene and provide you, for the first
time, the chance to lose the Celexa
weight gain. They are called JNK 5
and Optimum Solace. The JNK 5
provides the nutrients to reduce the
activation of the JNK gene and also
the proteins that reside upstream of
the JNK that continue to activate this
gene.
The Optimum Solace also reduces the
JNK activation and the saffron in the
supplement help bring you a relaxed
calm feeling. Without making you
tired.
These two supplements are also sold
at a massively reduced price so the
majority can afford their benefits. It is
time to take control back and be the
you, you want to be.
(1) Jan-Feb 2015;37(1):46-8.
doi:
10.1016/j.genhosppsych.2014.10.011.
Epub 2014 Oct 31.
Weight gain and associated factors in
patients using newer antidepressant
drugs
Objective: The aim of the present
study was to examine weight gain and
its association with clinical and
sociodemographic characteristics in
patients using newer antidepressants.
Methods: The study had a cross-
sectional design. A total of 362
consecutive psychiatric patients
taking antidepressant drugs for 6 to 36
months were included in the study.
Results: The prevalence rate of
weight gain was 55.2%; 40.6% of the
patients had a weight gain of 7% or
more compared to the baseline.
Overall, antidepressant use was
significantly related to increased body
weight. Specifically, citalopram,
escitalopram, sertraline, paroxetine,
venlafaxine, duloxetine and
mirtazapine, but not fluoxetine, were
associated with significant weight
gain. Multivariate logistic regression
analysis indicated that lower
education status, lower body mass
index at the onset of antidepressant
use and family history of obesity were
independent predictors of weight gain
≥7% compared to the baseline.
Conclusions: The study results
suggest that patients who take newer
antidepressants might have significant
problems related to body weight.
Keywords: Antidepressants; Body
mass index; Weight gain.
(2) JNK at the crossroad of obesity,
insulin resistance, and cell stress
response
Background: The cJun-N-terminal-
kinase (JNK) plays a central role in
the cell stress response, with
outcomes ranging from cell death to
cell proliferation and survival,
depending on the specific context.
JNK is also one of the most
investigated signal transducers in
obesity and insulin resistance, and
studies have identified new molecular
mechanisms linking obesity and
insulin resistance. Emerging evidence
indicates that whereas JNK1 and
JNK2 isoforms promote the
development of obesity and insulin
resistance, JNK3 activity protects
from excessive adiposity.
Furthermore, current evidence
indicates that JNK activity within
specific cell types may, in specific
stages of disease progression, promote
cell tolerance to the stress associated
with obesity and type-2 diabetes.
Scope of review: This review
provides an overview of the current
literature on the role of JNK in the
progression from obesity to insulin
resistance, NAFLD, type-2 diabetes,
and diabetes complications.
Major conclusion: Whereas current
evidence indicates that JNK1/2
inhibition may improve insulin
sensitivity in obesity, the role of JNK
in the progression from insulin
resistance to diabetes, and its
complications is largely unresolved. A
better understanding of the role of
JNK in the stress response to obesity
and type-2 diabetes, and the
development of isoform-specific
inhibitors with specific tissue
distribution will be necessary to
exploit JNK as possible drug target
for the treatment of type-2 diabetes.
Keywords: Autophagy; Diabetes;
Endoplasmic eeticulum stress;
Inflammation; MAPK; Oxidative
stress.
(3) Role of c-Jun N-terminal Kinase
(JNK) in Obesity and Type 2 Diabetes
Obesity has been described as a
global epidemic and is a low-grade
chronic inflammatory disease that
arises as a consequence of energy
imbalance. Obesity increases the risk
of type 2 diabetes (T2D), by
mechanisms that are not entirely
clarified. Elevated circulating pro-
inflammatory cytokines and free fatty
acids (FFA) during obesity cause
insulin resistance and ß-cell
dysfunction, the two main features of
T2D, which are both aggravated with
the progressive development of
hyperglycemia. The inflammatory
kinase c-jun N-terminal kinase (JNK)
responds to various cellular stress
signals activated by cytokines, free
fatty acids and hyperglycemia, and is
a key mediator in the transition
between obesity and T2D.
Specifically, JNK mediates both
insulin resistance and ß-cell
dysfunction, and is therefore a
potential target for T2D therapy.
Keywords: JNK; c-Jun N-terminal
kinase; glucotoxicity; inflammation;
insulin resistance; lipotoxicity;
obesity; type 2 diabetes.
(4) Adipocyte-Macrophage Cross-
Talk in Obesity
Obesity is characterized by the
chronic low-grade activation of the
innate immune system. In this respect,
macrophage-elicited metabolic
inflammation and adipocyte-
macrophage interaction has a primary
importance in obesity. Large amounts
of macrophages are accumulated by
different mechanisms in obese
adipose tissue. Hypertrophic
adipocyte-derived chemotactic
monocyte chemoattractant protein-1
(MCP-1)/C-C chemokine receptor 2
(CCR2) pathway also promotes more
macrophage accumulation into the
obese adipose tissue. However,
increased local extracellular lipid
concentrations is a final mechanism
for adipose tissue macrophage
accumulation. A paracrine loop
involving free fatty acids and tumor
necrosis factor-alpha (TNF-alpha)
between adipocytes and macrophages
establishes a vicious cycle that
aggravates inflammatory changes in
the adipose tissue. Adipocyte-specific
caspase-1 and production of
interleukin-1beta (IL-1beta) by
macrophages; both adipocyte and
macrophage induction by toll like
receptor-4 (TLR4) through nuclear
factor-kappaB (NF-kappaB)
activation; free fatty acid-induced and
TLR-mediated activation of c-Jun N-
terminal kinase (JNK)-related pro-
inflammatory pathways in CD11c+
immune cells; are effective in
macrophage accumulation and in the
development of adipose tissue
inflammation. Old adipocytes are
removed by macrophages through
trogocytosis or sending an "eat me"
signal. The obesity-induced changes
in adipose tissue macrophage
numbers are mainly due to increases
in the triple-positive CD11b+ F4/80+
CD11c+ adipose tissue macrophage
subpopulation. The ratio of M1-to-M2
macrophages is increased in obesity.
Furthermore, hypoxia along with
higher concentrations of free fatty
acids exacerbates macrophage-
mediated inflammation in obesity.
The metabolic status of adipocytes is
a major determinant of macrophage
inflammatory output.
Macrophage/adipocyte fatty-acid-
binding proteins act at the interface of
metabolic and inflammatory
pathways. Both macrophages and
adipocytes are the sites for active lipid
metabolism and signaling.
Keywords: C-C chemokine receptor
2 (CCR2); Chemokine (C-C motif)
ligand 2 (CCL2); Free fatty acids;
Hypoxia-inducible factor-1 alpha
(HIF-1alpha); Insulin-like growth
factor-1 (IGF1); Interleukin-6 (IL-6);
M1 macrophages; M2 macrophages;
Monocyte chemoattractant protein-1
(MCP-1); NOD-like receptor (NLR)
family protein (NLRP3); Obesity;
Toll like receptor 4 (TLR4); Tumor
necrosis factor-alpha (TNF-alpha);
Visceral adipose tissue.
(5) The Role of JNk Signaling
Pathway in Obesity-Driven Insulin
Resistance
Obesity is not only closely related to
insulin resistance but is one of the
main factors leading to the formation
of Type 2 Diabetes (T2D) too. The c-
Jun N-terminal kinase (JNK) family is
a member of the mitogen-activated
protein kinase (MAPK) superfamily.
JNK is also one of the most
investigated signal transducers in
obesity and insulin resistance. JNK-
centric JNK signaling pathway can be
activated by growth factors,
cytokines, stress responses, and other
factors. Many researches have
identified that the activated
phosphorylation JNK negatively
regulates insulin signaling pathway in
insulin resistance which can be
simultaneously regulated by multiple
signaling pathways related to the JNK
signaling pathway. In this review, we
provide an overview of the
composition of the JNK signaling
pathway, its regulation of insulin
signaling pathway, and the
relationship between the JNK
signaling pathway and other pathways
in insulin resistance.
Keywords: JNK signaling pathway;
insulin resistance; obesity; type 2
diabetes.
(6) JNK expression by macrophages
promotes obesity-induced insulin
resistance and inflammation
The cJun NH(2)-terminal kinase
(JNK) signaling pathway contributes
to inflammation and plays a key role
in the metabolic response to obesity,
including insulin resistance.
Macrophages are implicated in this
process. To test the role of JNK, we
established mice with selective JNK
deficiency in macrophages. We report
that feeding a high-fat diet to control
and JNK-deficient mice caused
similar obesity, but only mice with
JNK-deficient macrophages remained
insulin-sensitive. The protection of
mice with macrophage-specific JNK
deficiency against insulin resistance
was associated with reduced tissue
infiltration by macrophages.
Immunophenotyping demonstrated
that JNK was required for pro-
inflammatory macrophage
polarization. These studies
demonstrate that JNK in macrophages
is required for the establishment of
obesity-induced insulin resistance and
inflammation.
(7) The Pathogenesis of Obesity-
Associated Adipose Tissue
Inflammation
Obesity is characterized by a state of
chronic, low-grade inflammation.
However, excessive fatty acid release
may worsen adipose tissue
inflammation and contributes to
insulin resistance. In this case, several
novel and highly active molecules are
released abundantly by adipocytes
like leptin, resistin, adiponectin or
visfatin, as well as some more
classical cytokines. Most likely
cytokines that are released by
inflammatory cells infiltrating obese
adipose tissue are such as tumor
necrosis factor-alpha (TNF-alpha),
interleukin 6 (IL-6), monocyte
chemoattractant protein 1 (MCP-1)
(CCL-2) and IL-1. All of those
molecules may act on immune cells
leading to local and generalized
inflammation. In this process, toll-like
receptor 4
(TLR4)/phosphatidylinositol-3'-kinase
(PI3K)/Protein kinase B (Akt)
signaling pathway, the unfolded
protein response (UPR) due to
endoplasmic reticulum (ER) stress
through hyperactivation of c-Jun N-
terminal Kinase (JNK) -Activator
Protein 1 (AP1) and inhibitor of
nuclear factor kappa-B kinase beta
(IKKbeta)-nuclear factor kappa B
(NF-kappaB) pathways play an
important role, and may also affect
vascular endothelial function by
modulating vascular nitric oxide and
superoxide release. Additionally,
systemic oxidative stress, macrophage
recruitment, increase in the expression
of NOD-like receptor (NLR) family
protein (NLRP3) inflammasone and
adipocyte death are predominant
determinants in the pathogenesis of
obesity-associated adipose tissue
inflammation. In this chapter potential
involvement of these factors that
contribute to the adverse effects of
obesity are reviewed.
Keywords: Adipose tissue
macrophages (ATMs); Autophagy;
Ceramide; Endoplasmic reticulum
stress; Inducible nitric oxide synthase
(iNOS); Lipotoxicity; M1 adipose
tissue macrophages; Macrophage
migration inhibitory factor (MIF);
Monocyte chemoattractant protein 1
(MCP-1); Nuclear factor kappa B
(NF-kappaB); Obesity; Reactive
oxygen species (ROS); Saturated fatty
acid; Toll-like receptor 4 (TLR4);
Tumor necrosis factor alpha (TNF-
alpha); Vascular endothelial growth
factor (VEGF).