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WWW.CREATIVE-DIAGNOSTICS.COM
Obese Signaling Pathway
Creative Diagnostics
WWW.CREATIVE-DIAGNOSTICS.COM
xyPPT.yanj.cn ÐÂÀË΢²©£º @ ÁùÔÂÑ© _1
Obese
Obesity means a person who's very overweight, at least 20% higher
than it should be.
WWW.CREATIVE-DIAGNOSTICS.COM
NHANES
Obesity is a common problem in the US and worldwide.
According to National Health and Nutrition Examination Survey
(NHANES) data, it's estimated to affect around 30% adults and
around 20% children aged 10 to 11.
For children, rates of obesity have risen even
faster. Obesity is the second cause of death in
the world and has reached epidemic
proportions in recent years.
WWW.CREATIVE-DIAGNOSTICS.COM
Definition
Obesity and overweight involve an abnormal and excessive fat
accumulation that negatively affects the health status.
WWW.CREATIVE-DIAGNOSTICS.COM
1
5
4
3
2
Normal Weight
18.5~24.9
Overweight
25~29.9
Obese
30~34.9
Severe Obese
35~39.9
Morbidly Obese
40>
Definition
According to the World Health Organization
(WHO), if body mass index (BMI) is equal or
greater than 25 kg/m2, it is considered
overweight, whereas the BMI higher than
30 kg/ m2 defines obesity.
WWW.CREATIVE-DIAGNOSTICS.COM Ä£°æÑо¿Ôº
PPT CHART ACADEMY
6
It stems from a positive mismatch between
energy intake and energy expenditure.
Western societies are ¡°obesigenic¡± environments
where people have become sedentary while food
portions have grown ¡°super-sized¡± and highly
processed convenience foods and soft drinks
provide a glut of calories throughout the day.
Factors
WWW.CREATIVE-DIAGNOSTICS.COM
Factors
Actually, obesity is a consequence of complex interactions among
genetic, environmental, socio-economic, dietary factors, and
lifestyle factors .
WWW.CREATIVE-DIAGNOSTICS.COM
Genetic
Dietary factors
Socio-economic
Lifestyle factors
Factors
Environmental
WWW.CREATIVE-DIAGNOSTICS.COM
Genetic
Dietary factors
Socio-economic
Lifestyle factors
Environmental
Factors
WWW.CREATIVE-DIAGNOSTICS.COM
Factors
Lifestyle factors particularly in early life, such as
exposure to antibiotics, and other early life
environmental modifiers which may be linked with
epigenetic changes, are coming under scrutiny as risk
factors for obesity later in life.
The rapidity at which obesity is increasing in westernized
or socio-economically developed countries is not fully
explained by traditional theories of weight gain.
WWW.CREATIVE-DIAGNOSTICS.COM
Characteristics of obesity include
low-grade inflammation, altered
microbiota, and increased tone of
the endocannabinoid system.
Characteristics
WWW.CREATIVE-DIAGNOSTICS.COM
Obese
Signaling
Pathways
?01 FFAs signaling pathway
?02 Insulin signaling pathway
?03 SFAs signaling pathway
WWW.CREATIVE-DIAGNOSTICS.COM
Obesity individuals secrete less adiponectin than lean
individuals. The decreased production of adiponectin, in
combination with the inability of adipose tissue to store the
surplus free fatty acids (FFAs), can be considered to reflect
adipose tissue dysfunction. Under normal conditions,
adiponectin increases insulin sensitivity directly, by stimulating
tyrosine phosphorylation of the insulin receptor. Adiponectin,
binding to adipo-receptor R1/R2, can activate 5¡ä-AMP-activated
protein kinase (AMPK), leading to increased fatty acid
oxidation and decreased influx of FFAs into the liver.
Independent of AMPK activation, adiponectin decreases the
production of reactive oxygen species (ROS), which may result
in decreased activation of mitogen-activated-protein-kinase
(MAPK) and thereby inhibition of cell proliferation.
WWW.CREATIVE-DIAGNOSTICS.COM
Cells of the innate immune system produce cytokines and
other factors that affect insulin signaling and result in the
development of insulin resistance which is frequently seen
in obesity. Obesity induces lipolysis and release of pro-
inflammatory FFAs and factors, such as tumor necrosis
factor alpha (TNF-¦Á). TNF-¦Á initiates signaling through
tumor necrosis factor receptor 1 (TNFR1) with the
consequent regulation of gene expression, recruiting
TNFR1-associated death domain (TRADD), TNF receptor-
associated factor-2 (TRAF2), and receptor-interacting
protein (RIP). They then induce TGF¦Â-activated kinase 1
(TAK1) and TAK1-TAB complex which activates NF-¦ÊB
essential modulator (NEMO), IKK¦Á, and IKK¦Â. The
activation of the I¦ÊB kinase leads to phosphorylation of I¦ÊB
and release of NF-¦ÊB, which then translocates to the
nucleus and binds to the promoters of pro-inflammatory
genes and initiates transcription.
WWW.CREATIVE-DIAGNOSTICS.COM
Insulin binding to insulin receptor (IR),
leads to the activation of receptor
tyrosine kinase and receptor
phosphorylation, which enables the
binding of docking proteins such as
insulin receptor substrates (IRS). It then
stimulates cell proliferation through
several downstream signaling networks,
including the phosphatidylinositol 3-
kinase (PI3K) -AKT system, mammalian
target of rapamycin (mTOR), and the
MAPK systems.
WWW.CREATIVE-DIAGNOSTICS.COM
Saturated fatty acids (SFAs) are the major
type of fats including lauric, myristic, palmitic
and stearic acids. They can bind to Fetuin-A,
an endogenous ligand of toll-like receptor 2
(TLR2) or TLR4, and initiate transcription of
interferon regulatory factor 3 (IRF3) by
activating the myeloid differentiation primary
response protein 88 (MyD88)-TIR-domain-
containing adapter-inducing interferon-¦Â
(TRIF)-dependent pathway. TNF receptor-
associated factor-3 (TRAF3) is a ubiquitin
ligase recruited to both MYD88 and TRIF-
assembled signaling complexes. The IKK-
related kinases (TBK1) and IKK¦Å activate
IRF3, and activated IRF3 then translocates to
the nucleus and binds to target DNA
sequences.
WWW.CREATIVE-DIAGNOSTICS.COM
Obesity is a chronic disease and is associated with numerous comorbidities, including
type 2 diabetes mellitus (T2DM), cardiovascular disease, hypertension, and
dyslipidemia.
Therapy
Moreover, obesity is a risk factor for major causes of morbidity and mortality and increasing
evidence shows that a binge eating disorder (BED) affects a subset of obese patients.
The failure of these efforts points to the existence of additional, non-homeostatic
mechanisms that mediate feeding behavior. Indeed, redundancy in these pathways
makes obesity therapy difficult as it is further evidenced by the failure of newer drugs
targeting distinct aspects of these systems. Thus, the epidemic of obesity begs for novel
concepts and therapeutic targets that ideally treat ¡®food-use¡¯ disorders and related
comorbidities such as drug addiction and neuropsychiatric disorders.
WWW.CREATIVE-DIAGNOSTICS.COM
Do you want to know more about obesity?
Do not hesitate to contact us for any questions.
Email us at info@creative-diagnostics.com
Website: http://www.creative-diagnostics.com/
WWW.CREATIVE-DIAGNOSTICS.COM Ä£°æÑо¿Ôº
PPT CHART ACADEMY
THANK YOU
Website: http://www.creative-diagnostics.com/
Email: info@creative-diagnostics.com
45-1 Ramsey Road, Shirley, NY 11967, USA

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Obese creative diagnostics

  • 2. WWW.CREATIVE-DIAGNOSTICS.COM xyPPT.yanj.cn ÐÂÀË΢²©£º @ ÁùÔÂÑ© _1 Obese Obesity means a person who's very overweight, at least 20% higher than it should be.
  • 3. WWW.CREATIVE-DIAGNOSTICS.COM NHANES Obesity is a common problem in the US and worldwide. According to National Health and Nutrition Examination Survey (NHANES) data, it's estimated to affect around 30% adults and around 20% children aged 10 to 11. For children, rates of obesity have risen even faster. Obesity is the second cause of death in the world and has reached epidemic proportions in recent years.
  • 4. WWW.CREATIVE-DIAGNOSTICS.COM Definition Obesity and overweight involve an abnormal and excessive fat accumulation that negatively affects the health status.
  • 5. WWW.CREATIVE-DIAGNOSTICS.COM 1 5 4 3 2 Normal Weight 18.5~24.9 Overweight 25~29.9 Obese 30~34.9 Severe Obese 35~39.9 Morbidly Obese 40> Definition According to the World Health Organization (WHO), if body mass index (BMI) is equal or greater than 25 kg/m2, it is considered overweight, whereas the BMI higher than 30 kg/ m2 defines obesity.
  • 6. WWW.CREATIVE-DIAGNOSTICS.COM Ä£°æÑо¿Ôº PPT CHART ACADEMY 6 It stems from a positive mismatch between energy intake and energy expenditure. Western societies are ¡°obesigenic¡± environments where people have become sedentary while food portions have grown ¡°super-sized¡± and highly processed convenience foods and soft drinks provide a glut of calories throughout the day. Factors
  • 7. WWW.CREATIVE-DIAGNOSTICS.COM Factors Actually, obesity is a consequence of complex interactions among genetic, environmental, socio-economic, dietary factors, and lifestyle factors .
  • 10. WWW.CREATIVE-DIAGNOSTICS.COM Factors Lifestyle factors particularly in early life, such as exposure to antibiotics, and other early life environmental modifiers which may be linked with epigenetic changes, are coming under scrutiny as risk factors for obesity later in life. The rapidity at which obesity is increasing in westernized or socio-economically developed countries is not fully explained by traditional theories of weight gain.
  • 11. WWW.CREATIVE-DIAGNOSTICS.COM Characteristics of obesity include low-grade inflammation, altered microbiota, and increased tone of the endocannabinoid system. Characteristics
  • 12. WWW.CREATIVE-DIAGNOSTICS.COM Obese Signaling Pathways ?01 FFAs signaling pathway ?02 Insulin signaling pathway ?03 SFAs signaling pathway
  • 13. WWW.CREATIVE-DIAGNOSTICS.COM Obesity individuals secrete less adiponectin than lean individuals. The decreased production of adiponectin, in combination with the inability of adipose tissue to store the surplus free fatty acids (FFAs), can be considered to reflect adipose tissue dysfunction. Under normal conditions, adiponectin increases insulin sensitivity directly, by stimulating tyrosine phosphorylation of the insulin receptor. Adiponectin, binding to adipo-receptor R1/R2, can activate 5¡ä-AMP-activated protein kinase (AMPK), leading to increased fatty acid oxidation and decreased influx of FFAs into the liver. Independent of AMPK activation, adiponectin decreases the production of reactive oxygen species (ROS), which may result in decreased activation of mitogen-activated-protein-kinase (MAPK) and thereby inhibition of cell proliferation.
  • 14. WWW.CREATIVE-DIAGNOSTICS.COM Cells of the innate immune system produce cytokines and other factors that affect insulin signaling and result in the development of insulin resistance which is frequently seen in obesity. Obesity induces lipolysis and release of pro- inflammatory FFAs and factors, such as tumor necrosis factor alpha (TNF-¦Á). TNF-¦Á initiates signaling through tumor necrosis factor receptor 1 (TNFR1) with the consequent regulation of gene expression, recruiting TNFR1-associated death domain (TRADD), TNF receptor- associated factor-2 (TRAF2), and receptor-interacting protein (RIP). They then induce TGF¦Â-activated kinase 1 (TAK1) and TAK1-TAB complex which activates NF-¦ÊB essential modulator (NEMO), IKK¦Á, and IKK¦Â. The activation of the I¦ÊB kinase leads to phosphorylation of I¦ÊB and release of NF-¦ÊB, which then translocates to the nucleus and binds to the promoters of pro-inflammatory genes and initiates transcription.
  • 15. WWW.CREATIVE-DIAGNOSTICS.COM Insulin binding to insulin receptor (IR), leads to the activation of receptor tyrosine kinase and receptor phosphorylation, which enables the binding of docking proteins such as insulin receptor substrates (IRS). It then stimulates cell proliferation through several downstream signaling networks, including the phosphatidylinositol 3- kinase (PI3K) -AKT system, mammalian target of rapamycin (mTOR), and the MAPK systems.
  • 16. WWW.CREATIVE-DIAGNOSTICS.COM Saturated fatty acids (SFAs) are the major type of fats including lauric, myristic, palmitic and stearic acids. They can bind to Fetuin-A, an endogenous ligand of toll-like receptor 2 (TLR2) or TLR4, and initiate transcription of interferon regulatory factor 3 (IRF3) by activating the myeloid differentiation primary response protein 88 (MyD88)-TIR-domain- containing adapter-inducing interferon-¦Â (TRIF)-dependent pathway. TNF receptor- associated factor-3 (TRAF3) is a ubiquitin ligase recruited to both MYD88 and TRIF- assembled signaling complexes. The IKK- related kinases (TBK1) and IKK¦Å activate IRF3, and activated IRF3 then translocates to the nucleus and binds to target DNA sequences.
  • 17. WWW.CREATIVE-DIAGNOSTICS.COM Obesity is a chronic disease and is associated with numerous comorbidities, including type 2 diabetes mellitus (T2DM), cardiovascular disease, hypertension, and dyslipidemia. Therapy Moreover, obesity is a risk factor for major causes of morbidity and mortality and increasing evidence shows that a binge eating disorder (BED) affects a subset of obese patients. The failure of these efforts points to the existence of additional, non-homeostatic mechanisms that mediate feeding behavior. Indeed, redundancy in these pathways makes obesity therapy difficult as it is further evidenced by the failure of newer drugs targeting distinct aspects of these systems. Thus, the epidemic of obesity begs for novel concepts and therapeutic targets that ideally treat ¡®food-use¡¯ disorders and related comorbidities such as drug addiction and neuropsychiatric disorders.
  • 18. WWW.CREATIVE-DIAGNOSTICS.COM Do you want to know more about obesity? Do not hesitate to contact us for any questions. Email us at info@creative-diagnostics.com Website: http://www.creative-diagnostics.com/
  • 19. WWW.CREATIVE-DIAGNOSTICS.COM Ä£°æÑо¿Ôº PPT CHART ACADEMY THANK YOU Website: http://www.creative-diagnostics.com/ Email: info@creative-diagnostics.com 45-1 Ramsey Road, Shirley, NY 11967, USA