why is fat needed for health?
- 25% - 30 % fat is normal for middle aged woman - fat is needed for storage of food - insulation - source of hormones
what happens when one does not have enough fat ?
- infertility - miscarriage - death from infection - osteoporosis
what is the heritability of obesity?
- 0.77 This means 77% of the variation between individuals in a given environment is genetic
what is the BMI measurement of obesity?
BMI>30 morbid obesity BMI>40 BMI is the ratio of weight to height squared
what are the causes of obesity? controlled by genes
- behaviour ( feeding and physical activity) - physiology (resting metabolism and energy expenditure)
What are the three types of obesity?
Syndromic, Monogenic and Common
What is syndromic obesity commonly accompanied by?
Mental Retardation Dysmorphic features Prader Willi is the most common form
describe monogenic obesity:
- dominant or recessive single gene disorders - leptin was the first obese gene to be identified
how did scientists find out about leptin?
- there are circulatory systems of two mice, one lean and one obese connected - the obese mouse stopped eating and had reduced blood sugar - there was a transfer of blood borne lectin
Describe the action of leptin.
Leptin is hormone produced by adipocytes and travels to the brain to let the brain know how much fat is stored in the adipose cells and thus regulates feeding - More fat means more lectin so it tells your brain you don’t need to eat anymore - lectin also stimulates puberty - before puberty there is a build up of fat which sends permissive signal via leptin to the brain
why are some people not responsive to leptin?
- fat people have an insensitivity to leptin - the leptin receptor in the brain is deficient - some people have a genetic deficiency of the leptin receptor
What are some features of leptin deficiency?
- Low thyroid function - Immune problems - Incomplete/lack of puberty so infertile - uncontrollable appetite - leptin deficiency is very rare
What is the treatment for leptin deficiency?
Recombinant leptin
what controls body fat levels?
• The leptin-melanocortin adipostat regulates body fat levels.
Name some genes that cause monogenic obesity.
MRAP2 - recessive POMC PCSK1 MC4R - dominant and most common
What are Genome Wide Association Studies used for in relation to obesity?
- look at a persons genome and compare with a non obese person to identify natural variations and see if there are markers more common in one group - the method is hypothesis free - the process is not looking at mutations only at sequence variations - FTO is a big marker GWAS-identified single nucleotide polymorphisms explain only a small proportion of common obesity risk
what genetic factors might cause common obesity?
- Patients with syndromic forms of obesity have more Genomic Structural Variations
what do genomic structural variations include?
- Copy-Number Variation (CNVs) - deletions - extra copies of certain regions - inversions and translocations
what does a deletion at 16p11.2 cause?
-Onset of obesity at 8-10 years - Explains 1% of adult morbid obesity - risk of autism - Duplication carriers are more likely to be underweight
