Obesity

Question 1

———- is a leading preventable cause of death worldwide with increasing incidence.

Answer 1

Obesity

Question 2

Define obesity

Answer 2

Obesity is a medical condition in which excess fat has accumulated to the extent that it may have an adverse effect on health, leading to reduced life expectancy and increased health problems.

Question 3

HISTORICAL BACKGROUND
• Oxford dictionary- —————
• Obesity is from the Latin word, ———, which means “——, —— or ——”
• Historically as mankind struggled with food scarcity, obesity was then viewed as a sign of ——— and ————. Still seen as one in many parts of Africa particularly since the ——— epidermic began. Cultural practices like the ——— in Calabar further buttress this.

Answer 3

HISTORICAL BACKGROUND
• Oxford dictionary- very fat in a way that is not healthy
• Obesity is from the Latin word, Obesitas, which means “stout, fat or plump”
• Historically as mankind struggled with food scarcity, obesity was then viewed as a sign of wealth and prosperity. Still seen as one in many parts of Africa particularly since the HIV epidermic began. Cultural practices like the fattening room in Calabar further buttress this.

Question 4

Cultural practices like the fattening room in ——— further buttress this.

Answer 4

Calabar

Question 5

The ——- were the first to recognize it as a medical disorder.
•——— wrote that “corpulence is not only a disease itself, but the harbinger of others”

Answer 5

The Greeks were the first to recognize it as a medical disorder.
•Hippocrates wrote that “corpulence is not only a disease itself, but the harbinger of others”

Question 6

EPIDERMIOLOGY
• In ——, the WHO formally recognised obesity as a global epidemic.
• As of ——, the WHO estimates that at least how many adults are obese with higher rates among ——— than ———.
• Rate also increase with age up to at least — to — yrs

Answer 6

EPIDERMIOLOGY
• In 1997, the WHO formally recognised obesity as a global epidemic.
• As of 2008, the WHO estimates that at least 500 million adults are obese with higher rates among women than men.
• Rate also increase with age up to at least 50-60yrs

Question 7

EPIDERMIOLOGY CONT.
• Based on the study by ———— et al, in the year ——, conducted in ——-, among ——— adult residents, it was concluded that overweight and obesity are common in Nigerians, especially among ——— and the ———

Answer 7

EPIDERMIOLOGY CONT.
• Based on the study by Adedoyin R.A et al, 2009, conducted in Ile Ife, among 2097 adult residents, it was concluded that overweight and obesity are common in Nigerians, especially among females and the elderly

Question 8

CLASSIFICATION
• The ————- is used to classify obesity.

Answer 8

• The Body mass index (BMI)

Question 9

CLASSIFICATION
• The Body mass index (BMI) is used to classify obesity.
• Adults are considered obese when their BMI exceeds ——
• For children when the BMI exceeds the —th percentile for age and sex

Answer 9

30kg/m2
95th percentile

Question 10

BMI. CLASSIFICATION
<18.5.
18.5-24.9.
25.0-29.9.
30.0-34.9.
35.0-39.9.
≥40.0.

Answer 10

BMI. CLASSIFICATION
<18.5. Underweight
18.5-24.9. Normal weight
25.0-29.9. Overweight
30.0-34.9. Class I Obesity
35.0-39.9. Class II Obesity
≥40.0. Class III Obesity

Question 11

BMI. CLASSIFICATION
. Underweight
. Normal weight
. Overweight
. Class I Obesity
. Class II Obesity
. Class III Obesity

Answer 11

BMI. CLASSIFICATION
<18.5. Underweight
18.5-24.9. Normal weight
25.0-29.9. Overweight
30.0-34.9. Class I Obesity
35.0-39.9. Class II Obesity
≥40.0. Class III Obesity

Question 12

WHO MODIFICATION
• BMI —kg/m2 = Severe obesity.
• BMI —kg/m2 + Obesity related health conditions or
• BMI — to —kg/m2 =Morbid obesity.
• BMI — to — = Super obesity.

Answer 12

WHO MODIFICATION
• BMI ≥35kg/m2 = Severe obesity.
• BMI ≥35kg/m2 + Obesity related health conditions or
• BMI ≥ 40-44.9kg/m2 =Morbid obesity.
• BMI ≥45 or 50 = Super obesity.

Question 13

WHO MODIFICATION
• BMI ≥35kg/m2 = —— obesity.
• BMI ≥35kg/m2 + Obesity related health conditions or
• BMI ≥ 40-44.9kg/m2 =——- obesity.
• BMI ≥45 or 50 = ——- obesity.

Answer 13

WHO MODIFICATION
• BMI ≥35kg/m2 = Severe obesity.
• BMI ≥35kg/m2 + Obesity related health conditions or
• BMI ≥ 40-44.9kg/m2 =Morbid obesity.
• BMI ≥45 or 50 = Super obesity.

Question 14

List possible aetiologies

Answer 14

AETIOLOGY
•A combination of excess food energy intake, lack of physical activity, genetics, medical reasons (conditions and drugs) or psychiatric illnesses

Question 15

•Light shown on the subject since discovery of Leptin in ——year

Answer 15

1994

Question 16

Light shown on the subject since discovery of ——— in 1994

Answer 16

Leptin

Question 17

PATHOPHYSIOLOGY CONT.
• Several hormonal mechanism participate in the regulation of ——- and ——- intake, storage patterns of ——- tissue and development of —— resistance.
Hormones like ——, ——, ——,——, ——,, —— etc have been studied.

Answer 17

PATHOPHYSIOLOGY CONT.
• Several hormonal mechanism participate in the regulation of appetite and food intake, storage patterns of adipose tissue and development of insulin resistance.
Ghrelin, insulin, orexin, PPY 3-36, cholecystokinin, adiponectin etc have been studied.

Question 18

PATHOPHYSIOLOGY CONT.
• ——— and ——- are considered to be complementary in their influence on appetite.

Answer 18

PATHOPHYSIOLOGY CONT.
• Leptin and Ghrelin are considered to be complementary in their influence on appetite.

Question 19

• Ghrelin is produced in the —— in response to ———.
A short term mediator. T or F

Answer 19

• Ghrelin is produced in the stomach in response to stomach wall stretch.
F- A short term mediator.

Question 20

PATHOPHYSIOLOGY CONT.
• Leptin is produced by ——— to signal fat storage reserves in the body.
It’s a short term mediator of appetite control (ie to eat more when fat storages are low and less when high) T or F
• Leptin ——— more important than ——-

Answer 20

PATHOPHYSIOLOGY CONT.
• Leptin is produced by adipose tissue to signal fat storage reserves in the body.

F -It’s a long term mediator of appetite control

• Leptin resistance more important than deficiency

Question 21

PATHOPHYSIOLOGY CONT.
• Leptin and Ghrelin act on the ———of the hypothalamus
• Several circuits within the hypothalamus integrates appetite. The ———- pathway being the most understood.

Answer 21

PATHOPHYSIOLOGY CONT.
arcuate nucleus

The Melanocortin pathway

Question 22

PATHOPHYSIOLOGY CONT.
• Arcuate nucleus has output to the——— hypothalamus and ———hypothalamus
——— – Feeding centre
——— – Satiety centre
• Arcuate nucleus contains how many distinct neurons

Answer 22

PATHOPHYSIOLOGY CONT.
• Arcuate nucleus has output to the lateral hypothalamus (LH) and ventromedial hypothalamus (VMH).
LH – Feeding centre
• VMH – Satiety centre
• Arcuate nucleus contains 2 distinct neurons

Question 23

PATHOPHYSIOLOGY CONT.
FIRST ORDER NEURONES include;

Answer 23

PATHOPHYSIOLOGY CONT.
FIRST ORDER NEURONES
(1) Neuropeptide Y (NPY) and Agouti-related peptide(AgRP)
(2) Pro-opiomelanocortin (POMC) and amphetamine-regulated transcript (CART

Question 24

PATHOPHYSIOLOGY CONT.
FIRST ORDER NEURONES
(1) Neuropeptide Y (NPY) and Agouti-related peptide(AgRP): Has stimulatory inputs to —— and inhibitory to ——
(2) Pro-opiomelanocortin (POMC) and cocaine and amphetamine-regulated transcript (CART): Has stimulatory inputs to ——— and inhibitory to ——-.

Answer 24

PATHOPHYSIOLOGY CONT.
FIRST ORDER NEURONES
(1) Neuropeptide Y (NPY) and Agouti-related peptide(AgRP): Has stimulatory inputs to LH and inhibitory to VMH
(2) Pro-opiomelanocortin (POMC) and cocaine and amphetamine-regulated transcript (CART): Has stimulatory inputs to VMH and inhibitory to LH.

Question 25

PATHOPHYSIOLOGY CONT. • Both groups are regulated in part by ———.

Answer 25

Leptin

Question 26

PATHOPHYSIOLOGY CONT. • Both groups are regulated in part by Leptin. Leptin inhibits the ———group while stimulating the ——— group. • SECOND ORDER NEURONES • The efferent system; second order neurons that control ——— and ——— • Cytokines from the adipose tissue like ——,——,——,——,other chemokines and ——- hormones.

Answer 26

PATHOPHYSIOLOGY CONT. • Both groups are regulated in part by Leptin. Leptin inhibits the Neuropeptide Y/AgoutiRelatedPeptide(NPY/AgRP) group while stimulating the POMC/CART group. (Proopiomelanocortin/ cocaine and amphetamine related transcript.) • SECOND ORDER NEURONES • The efferent system; second order neurons that control food intake and energy expenditure. • Cytokines from the adipose tissue TNF,IL-6,IL-1,IL-18,other chemokines and steroid hormones.

Question 27

PATHOPHYSIOLOGY CONT. • LEPTIN DEFICIENCY; , certain individuals found to have this condition responded to ——— though much success has not been recorded in many others. • Loss of function mutation in the leptin gene; individuals with the ——— state usually exhibit ——— in the first months of life.

Answer 27

PATHOPHYSIOLOGY CONT. • LEPTIN DEFICIENCY; , certain individuals found to have this condition responded to leptin replacement though much success has not been recorded in many others. • Loss of function mutation in the leptin gene; individuals with the homozygous state usually exhibit morbid obesity in the first months of life.

Question 28

Leptin deficiency is not rare T or F

Answer 28

F • very rare

Question 29

PATHOPHYSIOLOGY CONT. • LEPTIN RECEPTOR • Mutation(homozygous); Truncation of the ——- usually abolishes leptin signalling, similar presentation to ———

Answer 29

receptor leptin deficiency

Question 30

PATHOPHYSIOLOGY CONT. • DEFECTS IN THE POMC PATHWAY; • ProOpioMelanocortin is a peptide expressed in the ——-(first order neurons),——-, ——-, ——-. Its also a precursor for the ——,—— and are produced by ———dependent cleavage. • Defects in POMC function cause ——-, ———- and ———-.

Answer 30

PATHOPHYSIOLOGY CONT. • DEFECTS IN THE POMC PATHWAY; • ProOpioMelanocortin is a peptide expressed in the brain(first order neurons),gut, placenta, pancreas. Its also a precursor for the ACTH,MSH and are produced by PC-1 dependent cleavage. • Defects in POMC function cause obesity, altered pigmentation and adrenal insufficiency.

Question 31

PATHOPHYSIOLOGY CONT. • ———mutations also cause obesity with adrenal insufficiency. • ——— receptor mutation(MSH receptor);cause dominant and recessive inherited non syndromic obesity with incomplete penetrance. This causes ——— obesity, its similar to the more common forms .Child usually manifests excessive hunger and food seeking behaviour from — to —months of life with associated increased growth velocity.

Answer 31

PATHOPHYSIOLOGY CONT. • PC-1 mutations also cause obesity with adrenal insufficiency. • MC4R receptor mutation(MSH receptor);cause dominant and recessive inherited non syndromic obesity with incomplete penetrance. This causes childhood obesity, its similar to the more common forms .Child usually manifests excessive hunger and food seeking behaviour from 6-8months of life with associated increased growth velocity.

Question 32

PATHOPHYSIOLOGY CONT. • GUT HORMONES; • GHRELIN; Acts by stimulating the ——— neurons increasing food intake. • Its level in the blood rises before meals and falls between — to —hours postprandially. .

Answer 32

PATHOPHYSIOLOGY CONT. • GUT HORMONES; • GHRELIN; Acts by stimulating the NPY\AgRP(orexigenic neurons) increasing food intake. • Its level in the blood rises before meals and falls between 1-2hours postprandially

Question 33

. There’s marked ———— suppression of ghrelin in obese individuals . This maintains the obesity by enhancing further ghrelin production.

Answer 33

. There’s marked postprandial suppression.

Question 34

PATHOPHYSIOLOGY CONT. • POLYPEPTIDE YY(PYY) : Secreted from the ——— cells of the ileum and colon its found to be low during ——- and increases shortly after ———. • Acts by stimulating the ———-neurons causing a decrease in food intake.

Answer 34

PATHOPHYSIOLOGY CONT. • POLYPEPTIDE YY(PYY) : Secreted from the endocrine cells of the ileum and colon its found to be low during fasting and increases shortly after food intake. • Acts by stimulating the POMC\CART neurons causing a decrease in food intake.

Question 35

PATHOPHYSIOLOGY CONT. • PolypeptideYY levels are found to generally low in individuals with ——- syndrome.

Answer 35

Prader-Willi syndrome. .

Question 36

• AMYLIN; • Peptide secreted with ——- also acts in a similar manner to ———

Answer 36

• AMYLIN; • Peptide secreted with insulin also acts in a similar manner to PolypeptideYY

Question 37

PATHOPHYSIOLOGY CONT. • ADIPONECTIN ,VISFATIN with other complement related acylation stimulating proteins generally have anti-———-, anti-———actions. • In obesity, the proinflammatory /antinflammatory balance is usually tipped towards ——— with increasing obesity and deficient adiponectin levels

Answer 37

PATHOPHYSIOLOGY CONT. • ADIPONECTIN ,VISFATIN with other complement related acylation stimulating proteins generally have anti-inflammatory, anti-atherogenic actions. • In obesity, the proinflammatory /antinflammatory balance is usually tipped towards inflammation with increasing obesity and deficient adiponectin levels

Question 38

PATHOPHYSIOLOGY CONT. • The essence of the storage of fatty acids as ———-in adipocytes is to enhance survival during periods of ————. • Fatty acids are also neatly tucked away as TAGs to prevent their ——— and —— stress.

Answer 38

PATHOPHYSIOLOGY CONT. • The essence of the storage of fatty acids as triacyglycerol (TAGs)in adipocytes is to enhance survival during periods of nutritional deprivation. • Fatty acids are also neatly tucked away as TAGs to prevent their toxicity and oxidant stress.

Question 39

PATHOPHYSIOLOGY CONT. • However the enhanced sympathetic state existent in obese individuals cause ———— of the excess storage of fat. Lipotoxicity ensues from the excess ——— and ———(to the endoplasmic reticulum and mitochondria) with widespread effects in the body organs like ———, ———, ——— etc.

Answer 39

PATHOPHYSIOLOGY CONT. • However the enhanced sympathetic state existent in obese individuals cause lipolysis of the excess storage of fat. Lipotoxicity ensues from the excess free fatty acids(FFAs) and oxidant stress(to the endoplasmic reticulum and mitochondria) with widespread effects in the body organs liver, pancreas, blood vessels etc.

Question 40

PATHOPHYSIOLOGY CONT. • Presence of the FFAs also inhibits ——— and prevent adequate clearance of serum triacylglycerols ;contributing further to the ————.

Answer 40

lipogenesis hypertriglyceridaemia.

Question 41

PATHOPHYSIOLOGY CONT. • ———- lipase also release FFAs from the elevated ———- (containing TAGs) in the serum. • This resulting lipotoxicity result in insulin ———- and insulin ———-.

Answer 41

PATHOPHYSIOLOGY CONT. • Endothelial lipoprotein lipase also release FFAs from the elevated β-lipoproteins (containing TAGs) in the serum. • This resulting lipotoxicity result in insulin receptor dysfunction and insulin resistance.

Question 42

INVESTIGATIONS BASELINE include:

Answer 42

INVESTIGATIONS BASELINE -Biochemical – renal, bone and liver -Full blood count -Fasting plasma glucose -Lipid profile -Serum free thyroxine and TSH -Serum uric acid

Question 43

INVESTIGATIONS FURTHER INVESTIGATIONS depending on clinical picture, include:

Answer 43

FURTHER INVESTIGATIONS depending on clinical picture -24hr urine free cortisol -ECG and chest X- ray -Respiratory function tests -plasma leptin- not routinely indicated

Question 44

TREATMENT The main treatment for obesity consists of ——— and ———. Drug therapy: -orlistat (inhibits pancreatic and gastric lipases) -Lorcaserin (5’HT agonist) -Phentermine and topiramate -———analogues, ——- inhibitors are also being subjected to further research studies. Surgery: ——— surgery and ———-. • —% may have complications • —% may require reoperation.

Answer 44

TREATMENT The main treatment for obesity consists of dieting and physical exercise. Drug therapy: -orlistat (inhibits pancreatic and gastric lipases) -Lorcaserin (5’HT agonist) -Phentermine and topiramate -leptin analogues, NPY inhibitors are also being subjected to further research studies. Surgery: Bariatric surgery and liposuction. • 17% may have complications • 7% may require reoperation.