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Exam 2- Endocrinology and cancer > Obesity > Flashcards

Obesity Flashcards

1
Q

What factors regulate food intake?

A
  • Physiological factors- hormones, peptide, energy stores, hypothalamus
  • Genetic factors- Leptin, MC4R
  • Psychological factors- mood
  • Social/environmental factors- lifestyle, work etc
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2
Q

What damage can lead to weight gain?

A

Damage to the hypothalamus- C20th- can damage the carefully coordinated balance between energy intake and energy expenditure

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3
Q

What is the role of leptin?

A

Leptin is a hormone that regulates normal weight and energy balance. It reduces food intake by increasing satiety.
- It is expressed in fat cells and synthesis is increased by glucocorticoids, insulin and oestrogens

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4
Q

What can a leptin deficiency cause?

A

Obesity- cause constant hunger and gaining of weight

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5
Q

What 2 groups of neutrons are involved in targeting the hypothalamus and energy control?

A
  • The two groups have opposing effects and need to be in balance

– Neuropeptide (NPY) and agouti-related peptide (AGRP) - cause increased food intake and decreased energy expenditure= Energy In
– pro-opiomelanocortin (POMC) and a- melanocyte-stimulating hormone (a-MSH) - cause decreased food intake and increased energy expenditure= Energy Out

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6
Q

What are the possible conditions associated with leptin and the associated treatments?

A
  • A leptin deficiency- VERY RARE- will cause severe childhood obesity.
    Can be resolved by giving recombinant Leptin
  • Mutations in the leptin receptor- these prevent leptin from being able to enter the cell and will lead to childhood obesity.
    Recombinant leptin will NOT help in this case
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7
Q

Are leptin levels higher or lower in those who are obese?

A

They are higher in those who are obese and can lead to leptin resistance as there can be:
defects in synthesis/ not recognised by the receptors
circulation problems
defects in leptin receptors

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8
Q

What 3 factors influence our energy expenditure?

A
  • Basal metabolic rate (BMR)- amount of energy expended by the body to maintain basic physiological functions over a period of 24 h.
    Is usually higher in men due to a leaner body mass (more muscle than fat)
  • Thermogenesis- generation of heat- meal-induced thermogenesis which is the increase in metabolic rate following food
  • level of physical activity- 20-40% of daily expenditure
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9
Q

What is basal metabolic rate and what factors influence a person’s BMR?

A

The amount of energy expended by the body to maintain basic physiological functions over a period of 24 h
- Body weight
- Body composition- muscle:fat ratio
- Age
- Gender
- Genetic factors

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10
Q

What is the definition of obesity?

A

The putting on of weight to the point it seriously endangers health

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11
Q

What BMI is classed as obese?

A

A BMI of over 30

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12
Q

How do you calculate an individuals BMI?

A

Weight (Kg)/ Height ( m2)

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13
Q

What are the WHO classifications of obesity?

A

Underweight= <18.5
Desirable= 18.5-24.9
Overweight= 25-29.9
Grade I Moderately Obese= 30-34.9
Grade II Severely Obese= 35-39.9
Grade III Morbidly Obese = >40

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14
Q

What are the statistics for levels of obesity in the UK?

A
  • Over 66% of adult men and 58% of adult women are obese
  • 1 in 5 reception children are obese and 1 in 3 year 6 children are obese
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15
Q

What complications can be caused by obesity?

A
  • Strokes
  • Hypertension
  • Coronary heart disease
  • Fertility and pregnancy problems
  • diabetes
  • cancers
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16
Q

What are the UK treatment recommendations for obesity?

A
  • Lower daily calorie intake by 600 kcal/day- depending on diet
  • Eat a healthy balanced diet
  • 150 minutes of moderate activity per week
17
Q

What are the targets of modern obesity drugs?

A
  • Appetite suppression
  • Decreased absorption
  • Increased metabolism
18
Q

What is the effect of lipase inhibition?

A

Lipase is an enzyme that catalyses the hydrolysis of triglycerides into glycerol and 3 fatty acids.
If lipase is inhibited, rat absorption will be reduced- useful for anti-obesity drugs

19
Q

What was the original natural product used to inhibit pancreatic lipase?

A

Lipstatin was discovered in 1987 from streptomycin toxytricini ( a gram-positive bacteria)

20
Q

What is the mechanism of action of the enzyme lipase and how does lipstatin inhibit this action?

A
  • The lipase enzyme active site contains a serine residue
  • This serine is activated by deprotonation by neighbouring residues.
  • It can then attack the triglyceride and cleave the ester bonds between the glycerol and 3 fatty acids
  • This forms a covalent acylserine intermediate which is then hydrolysed by water to release the fatty acid

BUT with lipstatin, the acylserine intermediate, is stable and so hydrolysis requires about 24 hours- so essentially is a irreversible inhibitor of breaking down the triglyceride

21
Q

Why is Lipstatin not on the market as a drug and what is its alternative?

A
  • Because lipstatin has multiple alkene groups, it is prone to oxidation on storage and in the body.
  • To solve this, Lipstatin is hydrogenated to form tetrahydrolipstatin= which forms the marketed drug known as ‘Orlistat’
21
Q

Why is Lipstatin not on the market as a drug and what is its alternative?

A
  • Because lipstatin has multiple alkene groups, it is prone to oxidation on storage and in the body.
  • To solve this, Lipstatin is hydrogenated to form tetrahydrolipstatin= which forms the marketed drug known as ‘Orlistat’
22
Q

What are the 2 methods of production of orlistat?

A
  • Semi-synthetic production- production of lipstatin via fermentation and then perform hydrogenation
  • Synthetic- totally synthetic production from simple startling materials. This produces Orlistat with a higher purity
23
Q

How is orlistat taken and any side effects of the drug?

A
  • Recommend in 1999 to take 120mg TDS- before meals
  • Was then approved to be sold OTC in 2009
  • Can produce significant side effects- increase in fatty stools, wind, faecal incontinence- though to act as an aversion therapy as encourages patients to avoid fats
24
Q

What is Fen/Phen?

A

A drug combination of fenfluramine and phentermine
- Fenfluramine- a serotonin-releasing agent
- Phentermine- Norinephrine-releasing agent
However, fenfluramine was found to be linked to hypertension and heart valve disease so was withdrawn creating thousands of lawsuits

Phentermine has since been approved for use in combination with topiramate in 2012 and has the largest weight loss of all FDA approved weight loss drugs

Exam 2- Endocrinology and cancer (28 decks)

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