This document discusses obesity, including its definition, prevalence, causes, characteristics, and related signaling pathways. Obesity is defined as having a body mass index of over 30 kg/m2 and affects around 30% of adults and 20% of children in the US. It results from an imbalance between calorie intake and expenditure and is influenced by genetic, dietary, socioeconomic, and lifestyle factors. Characteristics of obesity include low-grade inflammation and changes in gut microbiota and endocannabinoid signaling. The document examines signaling pathways related to obesity such as those involving free fatty acids, insulin, and saturated fats. Obesity is associated with various health conditions and is difficult to treat due to redundant pathways in the body
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.
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
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.
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/