Anti obesity models

Dr A.Sirisha, KIMS

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DR. SIRISHA.ADEPARTMENT OF PHARMACOLOGY

Anti obesity animal models

Dr A.Sirisha, KIMS

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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

Dr A.Sirisha, KIMS

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Introduction cntd…..

Orixogenic

Peptides: NPY, AgRP,

Orexins, Galanin,

βendorphins

Anorectic Peptides:

Corticotrophin, GLP1,

CCK

Dr A.Sirisha, KIMS

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PATHOPHYSIOLOGY OF OBESITY

Dr A.Sirisha, KIMS

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Dr A.Sirisha, KIMS

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Animal models

Dr A.Sirisha, KIMS

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Classification

Animal

models

In vivo

Diet induced

hypothalamic

Virus induce

d

genetic

monogenic

polygenic

transgenic

In vitro

Dr A.Sirisha, KIMS

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In vivo models

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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 months

Dr A.Sirisha, KIMS

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Hypothalamic obesity animal model

Hypothalamus

regulates food intake

through POMC nucleus

of pitutary gland

This is done by two

methods:

Chemical method

Surgical method

Dr A.Sirisha, KIMS

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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

Dr A.Sirisha, KIMS

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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

Dr A.Sirisha, KIMS

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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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Yellow mouse Zucker rat

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Genetic models cntd….

Polygenic models like

Japenese KK mouse

NZO mouse

OLETF rat

BSB model

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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

Dr A.Sirisha, KIMS

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In vitro models

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TO STUDY THE METABOLIC ACTIVITY IN BROWN ADIPOSE TISSUE

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

Dr A.Sirisha, KIMS

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TO STUDY Β3 AGONIST ACTIVITY:

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

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To study neuropeptide Y

Assay for neuropeptide Y

Neuropeptide Y stimulates apetite

Procedure: potential new drugs are targeted

against Y5, Y1 receptors

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To study the role of leptin

Assay for leptin mRNA level and plasma

leptin

Receptor: lepr or OB-R

Procedure: Radio Immuno Assay and

Northern blot after giving test drug

Dr A.Sirisha, KIMS

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Isolated adipocyte lines

Rat pre-adipocytes

Rat primary cultured mature adipocytes

T3-L1 adipocytes with mouse fibroblasts

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Thank you