This document discusses animal models used to study obesity. It begins by defining overweight and obesity according to BMI thresholds set by WHO. It then describes the pathophysiology of obesity and various animal models used to study it, including diet-induced, hypothalamic, virus-induced, genetic, transgenic, and in vitro models. Specific details are provided about procedures and parameters examined for several models, such as how diet-induced and hypothalamic models work. Genetic models discussed include yellow mouse, Zucker rat, and transgenic knockout models. In vitro models described aim to study metabolic activity in brown adipose tissue, beta-3 agonism, neuropeptide Y, and the role of leptin.

1. D R . S I R I S H A . A
D E P A R T M E N T O F P H A R M A C O L O G Y
Anti obesity animal
models
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2. Introduction
 Overweight and obesity are defined as abnormal or
excessive fat accumulation that may impair health.
 The WHO definition is:
a BMI greater than or equal to 25 is overweight
a BMI greater than or equal to 30 is obesity.
 It has multifactorial origin where energy intake is more
than energy expenditure
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3. Introduction cntd…..
 Orixogenic Peptides:
NPY, AgRP, Orexins,
Galanin, βendorphins
 Anorectic Peptides:
Corticotrophin, GLP1,
CCK
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4. PATHOPHYSIOLOGY
OF OBESITY
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6. Animal models
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7. Classification
Animal
models
In vivo
Diet
induced
hypotha
lamic
Virus
induced
genetic
monoge
nic
polygen
ic
transge
nic
In vitro
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In vivo models

9. Diet induced obesity model
 Procedure: rats are fed
high calorie cafeteria food
and sacrificed after 3
m0nths
 Parameters:
 Body weight, food intake,
locomotor activity, serum
insulinduring observation
time
 After sacrifice adipose cell
size, lipid content and
adipose tissue percentage
 Duration of
observation: 3 monthsDr A.Sirisha, KIMS
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10. Hypothalamic obesity animal model
 Hypothalamus regulates
food intake through POMC
nucleus of pitutary gland
 This is done by two
methods:
Chemical method
Surgical method
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11.  Surgical model
 Incission is made along
the base of brain 1mm
lateral to midline,
anterior to ear bars
exposing ventromedial
nucleus of
hypothalamus
 Chemical model
 Chemical agents used
are
Monosodium
glutamate 2mg/kg s.cx
5days
Gold thioglucose30-
40mg/kg ip single dose
Bipiperidyl mustard 5-
50mg/kg ip single dose
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12. Virus mediated obesity model
 Some virus target hypothalamus leading to the
damage of pathway regulating satiety and cause
obesity
 Virus: canine distemper virus
rous associated virus 7
avian adenovirus SMAM 1
ad 6
 Obesity develops in 8-10 weeks
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13. Genetic mediated obesity models
 The genetic models of obesity include
Monogenic models like
Yellow mouse- dominant gene, agouti locus
Obese mouse- recessive gene, chromosome 6
Zucker fatty rat- MC, recessive, Fa/fa
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14. Yellow mouse Zucker rat
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15. Genetic models cntd….
 Polygenic models like
Japenese KK mouse
NZO mouse
OLETF rat
BSB model
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16. Genetic models cntd….
 Transgenic models like
KOβ3gene responsible for white and brown
adipose tissue metabolism
KO Uncoupling pr0tein in brown fa
KO mouse lacking steroidogenic factor 1
Genes for leptin, growth hormone, leptin
receptor
 The gene used to knock out is diphtheria toxin A gene
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In vitro models

18. TO STUDY THE METABOLIC ACTIVITY IN
BROWN ADIPOSE TISSUE
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Assay for uncoupling protein and GLUT-4
Procedure: OLETF mice, age less than 10 weeks
test drug is given OD s/c and rat is
sacrificed at 14 weeks age
white and brown fat removed
Parameters: UCP and GLUT4 are measured with
western blot

19. TO STUDY Β3 AGONIST ACTIVITY:
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Assay for luciferase receptor gene assay and CAMP
response element
Β3 agonist causes weight loss by thermogenesis
Procedure: test drug is given to leptin gene
supressed transgenic mice

20. To study neuropeptide Y
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Assay for neuropeptide Y
Neuropeptide Y stimulates apetite
Procedure: potential new drugs are targeted
against Y5, Y1 receptors

21. To study the role of leptin
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Assay for leptin mRNA level and plasma leptin
Receptor: lepr or OB-R
Procedure: Radio Immuno Assay and Northern
blot after giving test drug

22. Isolated adipocyte lines
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Rat pre-adipocytes
Rat primary cultured mature adipocytes
T3-L1 adipocytes with mouse fibroblasts

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