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Defining obesity
Obesity - an excessive accumulation of body fat
sufficient to impair health
Risks - increase progressively from within the
healthy range
Adipose Tissue
White adipose tissue
Stored under the skin, in mesenteries and omentum, behind the
peritoneum
Primarily fat, also small amounts of protein and water
Stores triglycerides,
Brown adipose tissue
Large amounts in infants, small amounts in adults
Found primarily in scapular, sub-scapular areas
Heat production, cold adaptation, dissipation of excess energy
Normal
adipose tissue
Dysfunctional
adipose tissue
with increase in
mass
Increased number
of
enlarged
adipocytes
Dysfunctional
adipocyte
Lactate
Hypertension
Lipoprotein
Lipase
Angiotensinogen
Inflammation
Dyslipidemia
IL - 6
Arthritis
Asthma
Fat
Stores
Leptin
FFA
Insulin
Type 2 DM
TNF-
Adipsin
(Complement D)
ASCVD
Resistin
Estrogen
Adiponectin
Thrombosis
Plasminogen
Activator Inhibitor 1
(PAI-1)
DM=diabetes mellitus; FFA=free fatty acid; PAI-1=plasminogen activator inhibitor-1; TNF=tumor necrosis
factor alpha; IL-6=interleukin 6.
Slide: After Dr. G Bray
Adipocytokines
The term adipocytokines: adipocyte-derived biologically active
molecules which may influence the function as well as the
structural integrity of other tissues
Some examples of these substances are leptin, acylationstimulating protein (ASP), tumor necrosis factor-a (TNF-a),
plasminogen activator inhibitor-1 (PAI-1) and interleukin-6
Adipocytokines
Leptin is considered to be a fundamental signal of satiety to
the brain and has a variety of actions, ranging from
interference with sympathetic activity to hematopoiesis and
reproductive function
ASP increases triglyceride synthesis by increasing adipocyte
glucose uptake, activating diacylglycerol acyltransferase, and
inhibiting hormone-sensitive lipase
TNF:
PAI-1:
Resistin;
Weight
Weight is
is controlled
controlled by
by aa feedback
feedback system.
system.
Afferent
EC-CB1
Ghrelin
PYY
CCK
nn
Pancreas
Leptin
Adipose Tissue
Adrenal Steroids
Adrenal Cortex
Efferent
Autonomic
Nervous
System
External Factors *
food availability,
palatability
Vagus
Nerve
Hypothalamus, etc
Meal Size
Energy
Balance
and
Adipose
Stores
Food Intake
Energy
Expenditure
Adiponectin
Aronne LJ. Adapted from Campfield LA, et al. Science. 1998;280:1383-1387; and Porte D, et al. Diabetologia. 1998;41:863-881.
Food intake
energy expenditure
food intake
energy expenditure
BMI (kg/m2)
BMI Asia
Underweight
Normoweight
< 18.5
18.5 - 24.9
< 18.5
18.5 - 22.9
Overweight:
Pre-obese
25
25.0 29.9
23
23.0 24.9
Obese I
Obese II
30.0 - 34.9
5.0 - 39.9
25.0 - 29.9
> 30.0
Obese III
40.0
Waist Circumference
Waist circumference, independent of BMI /
weight, confers additional health risk with:
Glucose intolerance / Diabetes mellitus
Hypertension
Dyslipidemia
Important - WC in any weight category confers
similar risk
Regional Distribution
Causes of Obesity
Causes of Obesity
Set Point Theory
Genetics
If both parents are obese, then 80% risk that children are
obese.
If neither parent is obese, then risk is less than 10%
Twin studies Identical twins are more likely to weigh the
same as fraternal twins even when reared apart.
Food intake, tastes, BMR, number of fat cells, enzymes all
may be influenced by genetics.
Anthropologists have hypothesized are bodies are adapted to
storing fat due to times of famine.
Obesity
FFA
TG
HDL
Insulin resistance
Blood
pressure
Blood glucose
Type 2 diabetes
Cardiovascular
disease
Consequences of Obesity
Hypertension
Hypertension
Obesity
Sleep
Sleep Apnea
Apnea
Arthritis
Arthritis
Cardiovascular
Cardiovascular disease
disease
Social
Social disability
disability
Diabetes
Diabetes
Diabetes
Diabetes
complications
complications
Insulin
Insulin resistance/
resistance/
hyperinsulinemia
hyperinsulinemia
Cardiovascular
Cardiovascular
Disease
Disease
Hyperlipidemia
Hyperlipidemia
Caloric
Visceral
Obesity
intake
Free
fatty acids
Sedentary
lifestyle
Genetic
factors
Glucose
Lipids
Oxidative
stress
Inflammation
Insulin
resistance
Skin
Gout
Phlebitis
venous stasis
Portal
Fat Stores
FFA
Hepatic
Insulin
Clearance
Vascular
Constriction
Angiotensinogen
Plasma
Insulin
Renal Na+
Reabsorption
Angiotensin II
Angiotensin I
Hypertension
Obesity Prevention
and
Management
2. Pharmacological
Pharmacological therapy
of obesity
27-29.9
morbidities morbidities
With co-
morbidities
morbidities
Source: The Practical Guide to the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults.
Obesity Pharmacotherapy
Approved for Long-Term Use
System
Mechanism
Examples
Digestive
Inhibition of lipase
Orlistat(Xenical)
CNS
Inhibit norepinephrine,
Sibutramine(Meridia)
serotonin and
dopamine reuptake
Norepinephrine release
Phentermine, others
absorption
of fat
Xenical
Chitosan
absorption of
CHO
Acarbose
Gymenemic
acid
Anorexic drugs
Sibutramine
energy
expenditure by
Sibutramine
gastric
emptying by
Acarbose
Conclusion
Overweight and obese individuals are more likely to
develop type 2 diabetes than their normal-weight
counterparts.
In addition, the incidence of insulin resistance,
hyperinsulinemia, and the insulin resistance syndrome is
greater as BMI increases.
This is the at
riskpatient
Im talking about