Transcript HERSHEY, PA—In one of the largest product-liability rulings in U.S.... Corporation was ordered by a Pennsylvania jury Monday to pay...

HERSHEY, PA—In one of the largest product-liability rulings in U.S. history, the Hershey Foods
Corporation was ordered by a Pennsylvania jury Monday to pay $135 billion in restitution fees to
900,000 obese Americans who for years consumed the company's fattening snack foods.
Obesity
A disease on brain cells that encourage you to EAT
Prepared by,
ASHRAF
Overview
What is Obesity
What causes the disease
Who are obese
Genetic view of obesity
How to cure obesity
What is obesity?
Obesity is an excess of body fat that frequently in a
significant impairment of health
Man with more than 25% fat and woman with more than 30% fat are obese
Obese is a risk factor of chronic diseases:
Heart disease
Diabetes
High blood Pressure
Stroke
Some form of Cancer
It has more than one cause:
Genetic
Environmental
Psychological
Other factors may all play a part.
What causes obesity?
Four years ago scientists working with mice discovered a hormone, leptin, which appears to control
weight.
LEPTIN, produced by ADIPOCYTES (fat cells), and travels up to the appetite control center in the
brain, the hypothalamus.
LEPTIN is thought to act as a LIPOSTAT: as the amount of fat stored in ADIPOCYTES rises,
LEPTIN is released into blood and signals to the brain that the body has enough to eat
Therefore, body fat is maintained at a steady level, and makes dieting difficult. The mechanism can
be altered, but it is easier to make the body gain weight, than to lose it.
What causes obesity?
Most overweight people have high levels of LEPTIN in their body stream; therefore other molecules
also effect feeling of satiety and contribute to the regulation of body weight
In a recent study, Gene-Jack Wang, a physician of Brookhaven National Laboratory found that obese
people have fewer brain receptors for dopamine, a neurotransmitter that helps produce feelings of
satisfaction and pleasure
That implies: obese people may eat to stimulate their underserved reward circuits, just as addicts do
by taking drugs
Who are obese?
Eight out of 10 people are overweight in USA and 25% completely Sedentary
Half the British population is overweight
In USA:
58 million Overweight
40 Million Obese
3 Million morbidly Obese
Who are obese?
Well fit: people who meet basic activity level
recommendations
Fit to obese: Somewhere between the range
Extreme obese: people who are inactive or
need special care
60
50
40
30
20
10
0
People
Well fit
Fit to
obese
Extreme
obese
Genetic view of obesity
Ob1.seq -> 492 BP
DEFINITION Gallus gallus leptin (ob) mRNA, complete cds. ACCESSION
AF012727
Ob2.seq -> 504 BP
DEFINITION Sus scrofa leptin (ob) mRNA, complete cds.
ACCESSION
U59894
Ob3.seq -> 3800 BP
DEFINITION Homo sapiens leptin receptor (LEPR), mRNA.
ACCESSION
NM_002303
Ob4.seq -> 3426 BP
DEFINITION Homo sapiens leptin (obesity homolog, mouse) (LEP),
mRNA. ACCESSION
NM_000230
Ob5.seq -> 3393 BP
DEFINITION Mus musculus leptin receptor (Lepr), mRNA.
ACCESSION
NM_010704
Ob6.seq -> 561 BP
DEFINITION Mus musculus neuropeptide Y (Npy), mRNA.
ACCESSION
NM_023456
Ob7.seq -> 971 BP
DEFINITION Mus musculus adipocyte complement related protein
(Acrp30), mRNA. ACCESSION
NM_009605
Ob8.seq -> 3525 BP
DEFINITION Mus musculus leptin receptor (Lepr), mRNA.
ACCESSION
NM_146146
Ob9.seq -> 4517 BP
DEFINITION Homo sapiens adipose most abundant gene transcript 1
(APM1), mRNA. ACCESSION
NM_004797
Publish
Mus musculus neuropeptide (ob6.seq)
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gtggatctcttctctcacagaggcacccagagcagagcacccgccgctcagcgacgactgcccgcccgccacgatgctag
---------+---------+---------+---------+---------+---------+---------+---------+
V D L F S H R G T Q S R A P A A Q R R L P A R H D A R
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gtaacaagcgaatggggctgtgtggactgaccctcgctctatctctgctcgtgtgtttgggcattctggctgaggggtac
---------+---------+---------+---------+---------+---------+---------+---------+
* Q A N G A V W T D P R S I S A R V F G H S G * G V P
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ccctccaagccggacaatccgggcgaggacgcgccagcagaggacatggccagatactactccgctctgcgacactacat
---------+---------+---------+---------+---------+---------+---------+---------+
L Q A G Q S G R G R A S R G H G Q I L L R S A T L H
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caatctcatcaccagacagagatatggcaagagatccagccctgagacactgatttcagacctcttaatgaaggaaagca
---------+---------+---------+---------+---------+---------+---------+---------+
Q S H H Q T E I W Q E I Q P * D T D F R P L N E G K H
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cagaaaacgcccccagaacaaggcttgaagacccttccatgtggtgatgggaaatgaaacttgttctcccgacttttcca
---------+---------+---------+---------+---------+---------+---------+---------+
R K R P Q N K A * R P F H V V M G N E T C S P D F S K
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agtttccaccctcatctcatctcatcccctgaaaccagtctgcctgtcccaccaatgcatgccaccactaggctggactc
---------+---------+---------+---------+---------+---------+---------+---------+
F P P S S H L I P * N Q S A C P T N A C H H * A G L
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cgccccatttcccttgttgttgttgttgtatatatgtgtgtttaaataaagtaccatgcattcaaaaaaaaaaaaaaaaa
---------+---------+---------+---------+---------+---------+---------+---------+
R P I S L V V V V V Y M C V * I K Y H A F K K K K K K
a
-
Tree View
Phylogenic tree:
Ob1 -> Gallus gallus leptin
(AF012727)
Ob2 -> Sus scrofa leptin
(U59894)
Ob3 ->Homo sapiens leptin
receptor (NM_002303)
Ob4 ->Homo sapiens leptin
(NM_000230)
Ob5 -> Mus musculus leptin
receptor (NM_010704)
Pretty Look
Plurality: 2.00
Threshold: 1
AveWeight 1.00
AveMatch 1.00
PRETTY of: @/home/amashraf/.seqlab-mango/pretty_53.list
AvMisMatch 0.00
April 29, 2003 17:42
..
input_53.rsf{ob1}
input_53.rsf{ob2}
input_53.rsf{ob6}
Consensus
1
ATGTGCTGGA
ATGCGCTGTG
gtggatctct
ATG-GCTG--
GACCCCTGTG
GACCCCTGTG
tctctcacag
GACCCCTGTG
TCGACTTTGG
CCGATTCCTG
aggcacccag
-CGA-TCC-G
TCATACCTTG
TGGCTTTGGC
agcagagcac
TG-------C
TTTATGTTCA
CCTATCTGTC
ccgccgctca
CCTATGTTCA
AGCAGTGCCG
CTACGTTGAA
gcgacgactg
---AGT-C-G
TGCCAGATCT
GCCGTGCCCA
cccgcccgcc
-CCG-GC-C-
TCCAGGATGA
TCTGGAGAGT
acgatgctag
TC-AGG-TG-
90
CACCAAAACC
CCAGGATGAC
gtaacaagcg
C-A--AAGCC
input_53.rsf{ob1}
input_53.rsf{ob2}
input_53.rsf{ob6}
Consensus
91
CTCATCAAGA
ACCAAAACCC
aatggggctg
A-CA--AC--
CCATTGTCAC
TCATCAAGAC
tgtggactga
TCAT-A--AC
CAGGATCAAT
GATTGTCACC
ccctcgctct
CA-T-TCACT
GACATTTCAC
AGGATCAGTG
atctctgctc
A-CATT-CTC
ACACGTCGGT
ACATTTCACA
gtgtgtttgg
ACATGTC-G-
ATCCGCCAAG
CATGCAGTCT
gcattctggc
-----C----
CAGAGGGTCA
GTCTCCTCCA
tgaggggtac
----GGGTCA
CTGGCTTGGA
AACAGAGGGT
ccctccaagc
C-C-C--GG-
180
CTTCATTCCT
CACCGGTTTG
cggacaatcc
C--C--TTC-
input_53.rsf{ob1}
input_53.rsf{ob2}
input_53.rsf{ob6}
Consensus
181
GGGCTTCACC
GACTTCATCC
gggcgaggac
GGGCT---CC
CCATTCTGAG
CTGGGCTCCA
gcgccagcag
CCG--CTCAG
TTTGTCCAAG
TCCTGTCCTG
aggacatggc
T-----C--G
ATGGACCAGA
AGTTTGTCCA
cagatactac
A-G-T-C--A
CTCTGGCAGT
AGATGGACCA
tccgctctgc
--CTGGC-G-
CTATCAACAG
GACCCTGGCG
gacactacat
GAC-CTACAG
GTCCTCACCA
ATCTACCAAC
caatctcatc
-TCT-CCA-C
GCCTGCCTTC
AGATCCTCAC
accagacaga
ACCTGCC--C
270
CCAAAATGTG
CAGTCTGCCT
gatatggcaa
CA-A--GC--
input_53.rsf{ob1}
input_53.rsf{ob2}
input_53.rsf{ob6}
Consensus
271
CTGCAGATAG
TCCAGAAATG
gagatccagc
--GA--AA-G
CCAATGACCT
TGATCCAAAT
cctgagacac
CCA--GACAT
GGAGAATCTC
ATCGAATGAC
tgatttcaga
-GAGAAT--C
CGAGACCTCC
CTGGAGAACC
cctcttaatg
C--GA-AACC
TCCATCTGCT
TCCGGGACCT
aaggaaagca
TCCG--AGCT
GGCCTTCTCC
TCTCCACCTG
cagaaaacgc
---C-ACC-C
AAGAGCTGCT
CTGGCCTCCT
ccccagaaca
C-G--CT-CT
CTCTGCCTCA
CCAAGAGCTG
aggcttgaag
C---G-G--G
360
GACCAGTGGC
CCCCTTGCCC
acccttccat
-CCCTT-C-C
input_53.rsf{ob1}
input_53.rsf{ob2}
input_53.rsf{ob6}
Consensus
361
CTGCAGAAGC
CAGGCCAGGG
gtggtgatgg
CTGG-GA-GG
CAGAGAGCCT
CCCTGGAGAC
gaaatgaaac
CA-AGGA-AC
GGATGGCGTC
CTTGGAGAGC
ttgttctccc
-T-TG----C
CTGGAAGCCT
CTGGGCGGCG
gacttttcca
CTGG--GCC-
CACTCTACTC
TCCTGGAAGC
agtttccacc
--CT--AA-C
CACAGAGGTG
CTCCCTCTAC
ctcatctcat
CTCA----A-
GTGGCTTTGA
TCCACGGAGG
ctcatcccct
-TCAC---G-
GCAGGCTGCA
TGGTGGCCCT
gaaaccagtc
G-A-GC-GC-
450
GGGCTCTCTG
GAGCAGGCTG
tgcctgtccc
GGGCTGTCTG
input_53.rsf{ob1}
input_53.rsf{ob2}
input_53.rsf{ob6}
Consensus
451
CAGGACATTC
CAGGGGGCTC
accaatgcat
CAGGA-GCTC
TTCAACAGTT
TGCAGGACAT
gccaccacta
T-CA-CACTT
GGATATTAGC
GCTGCGGCAG
ggctggactc
GG-T-G-C-C
CCGGAATGCT
CTGGACCTCA
cgccccattt
C-GGAC-TCT
GA~~~~~~~~
GCCCTGGCTG
cccttgttgt
GCC-TG----
~~~~~~~~~~
CTGA~~~~~~
tgttgttgta
----------
~~~~~~~~~~
~~~~~~~~~~
tatatgtgtg
----------
~~~~~~~~~~
~~~~~~~~~~
tttaaataaa
----------
540
~~~~~~~~~~
~~~~~~~~~~
gtaccatgca
----------
input_53.rsf{ob1}
input_53.rsf{ob2}
input_53.rsf{ob6}
Consensus
541
~~~~~~~~~~
~~~~~~~~~~
ttcaaaaaaa
----------
561
~~~~~~~~~~ ~
~~~~~~~~~~ ~
aaaaaaaaaa a
---------- -
•ob1 = Galus gallus leptin
•ob2 = Sus scrofa leptin
•ob6 = Mus musculus neuropeptide
Compare
Compare between Homo
sapiens leptin receptor (ob3)
and Mus musculus leptin
receptor (ob5)
Characteristic Properties
Basic Characteristics of ob4.pep
(using seqlab pepsort)
Summary for whole sequence:
Molecular weight = 120742.11
Residues = 1093
Average Residue Weight = 110.469
Charged = 73
Isoelectric point = 10.45
Extinction coefficient = 195040
Localization potential of ob4.pep
(using psortII server)
Results of the k-NN Prediction (k = 9/23):
69.6 %: nuclear
8.7 %: mitochondrial
8.7 %: plasma membrane
4.3 %: vesicles of secretory system
4.3 %: cytoplasmic
4.3 %: endoplasmic reticulum
Distribution of 125 Blast hits
on the query sequence of ob3.pep
Blast hits of homo sapiens leptin
receptor
35 of them have score (bits) 2300 –
1000
Among higher score most of them
are of same class.
How to cure obesity?
Diets is the only cure of obesity
When diets fail, some people opt for radical surgery. However, this can cause serious problems such
as severe diarrhoea, problems with joints, haemorrhaging and scurvy.
In 1994 Phentermine and Fenfluramine were potent and users lost as much as a fifth of their body
weight. More than 6 million prescriptions were issued in 1996 alone.
Side effects: It causes a condition known as primary pulmonary hypertension, a constriction of the
blood vessels which can cause widespread tissue damage leading to death.
There are no drugs on the market that target the appetite centres of the brain selectively.
How to cure obesity?
Dr Arthur Campfield, of Hoffman-La Roche, said: "We believe that there is some place in the leptin
receptor that is broken so that obese people have almost no response when we give leptin into the
brain."
Fat mice can only be made thin again by forcing them to stop eating. People need a more humane
treeatment.
‘Olestra’ was one of the first products to be included in food to make it "fat free".
Olestra is a fat that cannot be absorbed. However, it causes diarrhoea, and inhibits the absorption of
nutrients.
Weight Loss Advice:
If you want to lose weight permanently, your diet program should be directed toward a slow, steady weight loss
According to official government dietary guidelines, you should expect to lose no more than 2 pounds of fat a
week
Losing more weight is no guarantee that weight loss is likely to be permanent.
References
NCBI
GCG
PubMed
SeqLab
PSORT
ClastalW
BBC
Wellness Intl. Network Ltd
Question?
Thank you