Genetics of Obesity

Question 1

How many people are obese?

Answer 1

24 in 100

Question 2

How many people are overweight?

Answer 2

36 in 100

Question 3

Name the two types of fat tissue

Answer 3

White Adipose tissue and Brown Adipose Tissue

Question 4

Good fat is?

Answer 4

Subcutaneous fat

Question 5

Bad fat is?

Answer 5

Visceral fat

Question 6

Where is subcutaneous fat found?

Answer 6

Just under the skin

Question 7

Where is visceral fat found?

Answer 7

Around the intra-abdominal area

Question 8

Describe three key points on white adipose tissue?

Answer 8

1. Energy storage
2. Lipid droplets forming one lipid vacuole
3. Excess calories cause lipid expansion

Question 9

What happens to energy in brown adipose tissue?

Answer 9

It is wasted

Question 10

Describe the lipid nature of brown adipose tissue

Answer 10

Multiple lipid droplets and numerous mitochondria essential for BAT fuel utilisation

Question 11

What kind of tissue is brown adipose tissue?

Answer 11

Catabolic tissue = burns lipids for energy wastage in the mitochondria

Question 12

How is energy wasted in brown adipose tissue?

Answer 12

excess calories are broken into fatty acids that enter mitochondria and undergo uncoupling

Question 13

Name the unique protein that brown adipose tissue expresses? And where is it found?

Answer 13

Uncoupling protein 1 (UCP1) OR (THERMOGENIN)

Mitochondria’s inner membrane

Question 14

Describe what UCP1 does?

Answer 14

UCP1 uncoupled oxidative phosphorylation from ATP synthesis. No ATP produced just H+ ions, thus producing a proton gradient. This wastes energy in the form of heat in thermogenesis.

Question 15

What environmental factors induce thermogenesis?

Answer 15

-cold
-hypercalorie diet
-photoperiodic changes
And pharmacological stimulation of beta adrenergic receptors on BAT

Question 16

How does UCP1 uncoupling waste energy?

Answer 16

Because it is metabolically inefficient thus burning calories

Question 17

What does enhanced BAT thermogenesis show?

Answer 17

Prevention of diet induced obesity and promotes weight loss

Question 18

People with less BAT tend to be?

Answer 18

Obesese/fat

Question 19

People near to the equator in hot climates tend to have more or less BAT?

Answer 19

Less - hence asians and black tend to get obese when they move to colder climates

Question 20

Why is visceral fat dangerous?

Answer 20

Because its located around the organs and due to its lipolytic nature the lipids can readily enter the organs.

Question 21

What kind of state in obese people does visceral fat cause?

Answer 21

An inflammatory state

Question 22

Visceral fat is more readily broken down true or false?

Answer 22

TRUE

Question 23

What kind of fat is more susceptible to hypertrophy?

Answer 23

Visceral fat - cells take up adipose and get larger

Question 24

Subcutaneous fat cells are smaller or larger than visceral fat cells?

Answer 24

Smaller

Question 25

What process is subcutaneous fat cells liable to?

Answer 25

Lipolysis- break down of lipids involving hydrolysis of triglycerides to glycerol and free fatty acids

Question 26

When subcutaneous fat cells undergo hypoplasia what happens?

Answer 26

They increase in the number of cells causing it to expand. The creased blood ad nerve supply prevents inflammation

Question 27

What are th major risks of abdominal obesity?

Answer 27

Cardiovascular Disease and diabetes

Question 28

What problems arise from central obesity?

Answer 28

- endothelial dysfunction - hypertension - insulin resistance - atherogenic dyslipidaemia - inflammatory profile - pro-thrombic state

Question 29

Inflammation is caused by?

Answer 29

Increased number of lipids in the muscle

Question 30

What does obesity inflammation lead to?

Answer 30

The build up of cytokines leading to increased fatty acid metabolism to remove triglycerides, producing a reactive oxygen species that effects th muscles ability to take up glucose causing type 2 diabetes

Question 31

What is Berardinelli-seip syndrome?

Answer 31

Congenital generalised lipodystrophy type 2 - complete lack of subcutaneous fat. Autosomal recessive

Question 32

What causes berardinelli-seip syndrome?

Answer 32

Mutation in the BSCL2/seipin gene

Question 33

What happens in Berardinelli-seip syndrome?

Answer 33

The person cannot produce adipose cells, thus fat cannot be stored in adipose cells, therefore fat goes into the major organs causing an insulin resistance.

Question 34

What did the genetic study of obesity in twins conclude?

Answer 34

That obesity must be a genetic predisposition, as there was little variation within twins but lots of variation between twins!

Question 35

What is leptin?

Answer 35

A hormon made by adipose cells that is used to regulate energy balance by inhibiting hunger. Its actions are opposed by ghrelin - the hunger hormone.

Question 36

What is the action of leptin?

Answer 36

It is secreted by the adipose tissue and acts on the hypothalamus where it synapses with neurones to regulate energy metabolism in the periphery.

Question 37

In 1997 what's the disease discovered that occurred due to a mutation in leptin?

Answer 37

Congenital leptin deficiency - found to be associated with severe early onset obesity.

Question 38

What type of mutation did M.Wabitsch et.al., find?

Answer 38

A novel mutation in which leptin was still produced normally but was not functional - couldn't bind the receptor.

Question 39

What system does leptin function in?

Answer 39

The leptin - melanocortin system - vital for energy homeostasis

Question 40

What is the name of the hormone which is a potent stimulator of appetite?

Answer 40

NPY

Question 41

List the mutation in the leptin-melanocortin system?

Answer 41

``` Monogenic (non-syndromic) obesity mutations. LEP LEPR POMC MC4R PCSK1 BDNF NTRK2 SIM1 ```

Question 42

monogenic obesity is...

Answer 42

...very rare

Question 43

Prader-willi is caused by?

Answer 43

paternal deletions of Ch15q11-q12

Question 44

Prader-willi causes

Answer 44

Short stature Hyperphagia - abnormal great desire for food Central Obesity

Question 45

What is Bardet-Biedl syndrome (BBS) caused by?

Answer 45

Several causal mutation at various loci (14t)

Question 46

BBS causes?

Answer 46

Cilipopathy Hypogonadism Early onset obesity Renal Disease