This document discusses the relationship between obesity and genetics. It first defines obesity and provides markers of obesity like waist circumference and BMI. It then discusses the epidemiology of obesity worldwide and in Pakistan specifically. Several studies on obesity prevalence in different regions and provinces of Pakistan are mentioned. The etiology of obesity is explained as involving both genetic and environmental factors. Several genes associated with obesity are identified. The pathophysiology involves hormones like leptin, resistin and adiponectin that regulate appetite and metabolism. The genetic and environmental factors that influence obesity development and prevalence are summarized concisely.

1. RELATION BETWEEN OBESITY AND
GENETICS
BY
MAHAM ABBASI(01)
SADAQAT BIBI(12)
MAHNOOR HAYAT(14)

2. OBESITY:
Obesity is a state of excess adipose
tissue mass. Although often viewed as
equivalent to increased body weight.
Obesity is the result of accumulation of
body fat over time that results from
chronic energy imbalance that arises
due to calories consumed exceeding
calories expended.
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3. MARKERS OF OBESITY
• Waist circumference and BMI etc.
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4. 4

5. • EPIDEMIOLOGY:
Overall, about 13% of the world’s adult population
(11% of men and 15% of women) were obese in
2014.The worldwide prevalence of obesity more than
doubled between 1980 and 2014.
Worldwide, at least 2.8 million people die each year
as a result of being overweight or obese. While less
than 2.7 million deaths have been reported due to
AIDS by less than 1 million for cancer.
There are two types of obesity:
1. Android obesity: male pattern or abdominal obesity.
2. Gynoid obesity: female pattern or gluteal obesity.
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6. OBESITY IN PAKISTAN:
 In Pakistan alone,
one in four adults is
overweight or obese.
According to WHO
estimates, 26% of
women and 19% of
men are
obese(BMI>25)
in Pakistan.
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7. OBESITY IN PAKISTAN:
• A study conducted in northern areas of Pakistan had described an age-adjusted
prevalence of overweight and obesity around 13.5% and 14.1% for men and women,
respectively.
• Another study was conducted in Multan, Pakistan considering the new recommended
BMI cut-off for Asians found 46% of the people were overweight and obese.
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8. PERCENTAGE OF OVERWEIGHT
AND OBESE BY REGION
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9. PERCENTAGE OF OVERWEIGHT
AND OBESE ADULTS BY
PROVINCE
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10. ETIOLOGY :
• Body weight is
ultimately determined
by the interaction of
genetic, environmental
and psychosocial
factors acting through
the physiological
mediators of energy
intake and expenditure.
• Like many other
medical conditions,
obesity is the result of
an interplay between
genetic and
environmental factors. 10

11. 11

12. RATIO OF GENETIC
FACTORS INVOLVED IN
OBESITY:
Studies suggest that genetics
contribute to 30-50% of
obesity.
More than 50 genes are
discovered that are strongly
associated with obesity.
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13. • Some reasons for the increasing prevalence of obesity
(obesogenic environment)
Diet :
Total food energy consumption has been found to be related to
obesity.
Most of this extra food energy is from an increase
in carbohydrate consumption rather than fat consumption.
The primary sources of these extra carbohydrates are
sweetened beverages, which now account for almost
25 percent of daily food energy in young adults
and potato chips.
13

14. Increasing energy intake:
• Increased portion sizes,
increased Snacking and loss of
regular meals, increased Energy
dense food (mainly fat), and
increased affluence (Richness).
These conditions make the
energy intake more than the
expenditure which leads to
storing the excess energy as fat
in the body.
14

15.  Pregnancy: Some women after the
baby is born have an increasing in
their weight, and if they don’t lose
that weight, with many pregnancies
after that, they may become obese.
Lack of sleep: This cause
disturbances in the body hormones
and increase the appetite. you also
may crave to height calories food.
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16. Sedentary lifestyle (decreased energy
expenditure):
 Insufficient exercise.
Increased car ownership,
Decreased walking to school/work,
 increased Automation; decreased
manual labor.
Decreased sports in schools.
 Increased time spent on computer
games and watching TV.
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17. Drugs causing obesity:
These include insulin, sulfonylureas, thiazolidinediones, a typical antipsychotics,
antidepressants, steroids, certain anticonvulsants (phenytoin and valproate),
pizotifen, and some forms of hormonal contraception .
Infectious agents causing obesity:
An association between viruses and obesity has been found in humans and several
different animal species. The amount that these associations may have contributed
to the rising rate of obesity is yet to be determined.
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18. Hypothyroidism, which is a condition in which the thyroid gland does
not produce enough thyroid hormones which have important role in
regulating metabolism and energy expenditure, is one of the conditions
leading to obesity.
Cushing’s syndrome is another condition causing obesity, in this
disorder there will be excessive production of the hormone Cortisol by
the adrenal gland or exogenous cortisol is taken as medication leading
to change in the fat metabolism.
Endocrine factors leading to obesity:
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19. •Medical conditions: some diseases and syndromes lead the body to store more
fat and gain weight like Cushing syndrome. Some diseases low the metabolic rate in the
body and low the amount of burned calories every day such as the hypothyroidism. And
some diseases lead the patient to low his activity, such as the arthritis or maybe the
patients with paraplegia.
•Genetics: Genes affect the amount of body fat we store and where to store,
•Age: obesity could occur at any age, but when we get age, we lose more amount of
muscles built. more amount of muscles give higher rate of metabolism and calories
burning. When we lose them, we reduce the calories burning and tend to fill the body
with fat.
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21. EFFECTS OF
OBESITY
• All-causes of death (mortality)
• High blood pressure (hypertension)
• Type 2 diabetes
• Coronary heart disease
• Stroke
• Osteoarthritis (a breakdown of
cartilage and bone within a joint)
• Sleep apnea and breathing problems
• Many types of cancers
• Mental illness
• Body pain and difficulty with
physical functioning
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24. PATHOPHYSIOLOGY:
There are many possible pathophysiological mechanisms involved in the development and maintenance of
obesity.
Leptin And Gherlin:
Leptin and ghrelin are considered to be complementary in their influence on appetite, with ghrelin produced
by the stomach modulating short-term appetitive control (i.e., to eat when the stomach is empty and to stop
when the stomach is stretched).
Leptin is produced by adipose tissue to signal fat storage reserves in the body and mediates long-term
appetitive controls (i.e., to eat more when fat storages are low and less when fat storages are high).
.
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26. • Although administration of leptin may
be effective in a small subset of obese
individuals who are leptin deficient,
most obese individuals are thought to be
leptin resistant and have been found to
have high levels of leptin.
• While leptin and ghrelin are produced
peripherally, they control appetite
through their actions on the central
nervous system. In particular, they and
other appetite-related hormones act on
the hypothalamus, a region of the brain
central to the regulation of food intake
and energy expenditure.
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27. LEPTIN
Leptin acts on receptors in the hypothalamus of the brain where it:
counteracts the effects of neuropeptide Y (a potent feeding
stimulant secreted by cells in the gut and in the hypothalamus).
 counteracts the effects of anandamide (another potent feeding
stimulant that binds to the same receptors as THC, the active
ingredient of marijuana)
 promotes the synthesis of α-MSH, an appetite suppressant.
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28. RESISTIN
In humans, Resistin is primarily a product of macrophages, not fat cells, encoded by the
RETN gene.
Resistin causes insulin resistance
There is a strong association in humans between elevated levels of Resistin, Obesity, and Type
2 diabetes
over 80% of the people with NIDDM are obese
ADIPONECTIN
In humans it is encoded by the ADIPOQ gene and it is produced in primarily in adipose tissue,
but also in muscle, and even in the brain.
 Its circulating levels are 1000-fold higher than leptin or insulin.
It plays a role in increasing energy expenditure and decreasing body weight also increases
insulin sensitivity
Thiazolidinediones increase this hormone via PPAR-gamma
 Its level are increased after starvation. 28

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30. REGULATION OFAPPETITE
Appetite – lateral hypothalamus
Satiety – ventromedial hypothalamus
Destruction of LHA leads to starvation and death.
Destruction of VMA leads to obesity
OTHER CENTRES IN REGULATION OF APPETITE :
1. Arcuate Nuclei- primary site for action of leptin and insulin.
2. Para Ventricular Nuclei- AMP kinase mediated appetite regulation
3. Dorsomedial Hypothalamic Nuclei destruction leads to hyperphagia and obesity
NEURO HUMORAL FACTORS IN OBESITY
Adipokines – Leptin, Resistin, Adiponectin, Retinol binding Protein 4, Visfatin
Pancreatic hormones – Insulin, Pancreatic Polypeptide (PP/PYY/NPY)
Gut Hormones – Incretins
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32. GENETIC :
• Polymorphisms in various genes controlling appetite and metabolism
predispose to obesity when sufficient food energy is present.
• A few rare single gene disorders have been identified which led to severe
childhood obesity.
• People with two copies of the FTO gene (fat mass and obesity associated
gene) have been found on average to weigh 3–4 kg more and have a 1.67-
fold greater risk of obesity compared with those without the risk allele
• Obesity is a major feature in several syndromes, such as Prader–Willi
syndrome, Bardet–biedl syndrome, Cohen syndrome, and MOMO
syndrome: Macrosomia (excessive birth weight), Obesity, Macrocephaly
(excessive head size) and Ocular abnormalities.
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33. 33

34. Genetic factors
• Genetic factors play a permissive role and interact with
environmental factors to produce obesity account for 30 to 50% .
• A few specific syndromes and single-gene defects which are linked
to obesity in childhood have been Identified.
Single gene disorder
• Leptin deficiency (LEP)
• Leptin receptor deficiency (LEPR).
• Melanocortin receptor 4 haploinsufficiency (MC4R).
• Pro-opiomelanocortin deficiency (POMC)
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35. THE “THRIFTY GENE’’ HYPOTHESIS:
Scientists have found several genes that regulate how the body captures, stores and releases energy
from food. The origin of these genes is ancient. There is a concept of the “thrifty gene”.
The theory suggests that the thrifty gene might have helped ancestors of present-day humans survive
occasional famines.
It is this same gene that is exposed to excess energy intake. It is now challenged by environments in
which food is plentiful year-round. This could result in increased storage of the energy in form of fat
giving rise to the obesity epidemic.
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36. Genome wise associated studies(GWAS) have accelerated the discovery of genetic variants
associated with susceptibility to common complex diseases, such as obesity.
Following the first robust GWAS of BMI(Body Mass Index) and risk of obesity identified in
2007, GWAS has delivered 70 additional common loci associated with a wide range of obesity-
related traits. These loci highlight a variety of molecular and physiological mechanisms involved
in shaping these traits.
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38. Monogeneic obesity
Monogenic obesity is described as rare and severe early-onset
obesity with abnormal feeding behavior and endocrine disorders.
This is mainly due to autosomal recessive mutations in genes of the
leptin-melanocortin pathway which plays a key role in the
hypothalamic control of food intake.
Melanocortin 4 receptor(MC4R)-linked obesity is characterized by
the variable severity of obesity and no notable additional
phenotypes. Mutations in the MC4R gene are involved in 2-3% of
obese children and adults; the majority of these are heterozygous.
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39. monogenic causes of obesity
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40. Monogenic Human Obesity Syndrome
Congenital Leptin Deficiency
• Homozygous for a frameshift mutation in the obesity gene present on chromosome 7.
• An intense drive to eat-never satisfied.
• Advanced skeletal maturation
• Impaired T cell mediated immunity
.
Melanocortin 4 Receptor Deficiency
• Mutation in the MC4R appear to be the commonest monogenic cause of obesity.
•Increase in lean body mass.
•Increased bone mineral density
•increased linear growth throughout childhood
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42. POMC Deficiency
• Pro-opiomelanocortin (POMC) is produced by
hypothalamic neurons of the arcuate nucleus
• presented in neonatal life with adrenal crisis due to isolated
ACTH deficiency
• hyperphagic, developing early-onset obesity
• pale skin and red hair due to the lack of MSH function
Prohormone Convertase 1 Deficiency
• childhood obesity
• abnormal glucose homeostasis
• very low plasma insulin
• elevated levels of pro insulin
• hypogonadotropic hypogonadism
• hypocortisolemia
• elevated levels of POMC 42

43. POLYGENEIC OBESITY
• Gene variants (alleles) that have a small influence on body
weight are termed polygenes.
• Alleles associated with obesity are common in the general
population.
• Those polygenic variants presumably account for most of the
genetic variation relevant in human body weight regulation.
• Causes obesity via the interaction of several of such
polygenic variants and their combined interaction with
environmental factors.
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44. 44

45. Obesity in the mouse model:
 Mouse model is used to research the effect of genetic changes on
metabolism
 In the rodent DNA, 166 genes have been identified that, when mutated or
expressed as transgenes in the mouse, result in phenotypes that affect
body weight and adiposity.
 Obesity in rodents may be due to hepatic lipase activity
 Some obesity is due to influences on food intake.
 Genetic influences may lead to late-onset (Fob3a) or early-onset (Fob3b)
obesity in laboratory animals.
 Gene mutations may influence insulin and lipids or otherwise influence
body weight.
 Leptin level or receptors may be influenced leading to obesity.
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46. PREVENTION:
Different policy approaches may be needed to
achieve improvements in food and physical
activity environments, such as choosing
healthier foods (whole grains, fruits and
vegetables, healthy fats and protein sources) and
beverages, limiting unhealthy foods (refined
grains and sweets, potatoes, red meat, processed
meat) and beverages (sugary drinks), increasing
physical activity, limiting television time, screen
time, and other “sit time, improving sleep,
reducing stress. The latter two have role in
hormonal regulation of the body associated with
fat storage and weight.
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48. MANAGEMENT :
 General Measures: The doctor should assess the degree of health
risk from BMI and waist circumference, and Assessment of motivation
to lose weight.
 Diet restriction: Diet restriction is an important method for
obesity management. The diet should be of low fat, high complex
carbohydrates and high fiber quality.
 Exercise: improves long term results of weight loss treatment. With
use, muscles consume energy derived from both fat and glycogen. Due
to the large size of leg muscles, walking, running, and cycling are the
most effective means of exercise to reduce body fat.
 Medications: Should reduce the use of unnecessary medications.
 Surgery: ‘Bariatric’ surgery to reduce the size of the stomach is by
far the most effective long-term treatment for obesity.
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50. CONCLUSION
Obesity is a leading cause of mortality globally causing death of people
by millions annually more than AIDS and cancer.
It affects both male and female and it increasingly affects both adults
and children.
 Obesity is caused by many interacting factors including genetics, diets
with high energy intake and low energy expenditure, endocrine factors
such as in Cushing’s syndrome, drugs such as steroids.
Obesity can be managed by many ways including proper diet, exercise,
medications, and bariatric surgery.
It can be prevented by choosing good, healthy foods and beverages and
staying away from bad, unhealthy ones, regular exercise, staying away
from sedentary lifestyle, improving sleep, and reducing stress in your life.
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https://www.
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