Corso di Basi biochimiche dell'azione dei farmaci
Chimica e Tecnologia Farmaceutiche (DM 270)
Dipartimento di Farmacia
‘’MOLECULAR BASIS OF OBESITY’’
The leptin melanocortin pathway and human genetics
Antenori Paola
Matricola 470178
Pisa 13.03.2014
• Definition
• Body mass regulation
Orexigenic and anorexigenic peptides production
• Obesity as heritable disorder
Monogenic and polygenic forms of obesity
Overweight and obesity are defined as abnormal or
excessive fat accumulation that may impair healt [1]
In 1997, the World Health Organization officilay declared obesity to
be a global epidemic.
The new IASO/IOTF (International Association for the Study
of Obesity/International Obesity Task Force) analysis estimates that
in 2010 approximately 1.0 billion adults are overweight (BMI 2529.9 Kg/m²), and a further 475 million are obese (BMI >30 Kg/m²) [2]
1.
2.
http://www.who.int
http://www.worldobesity.org/iotf/
Obesity prevalence worldwide [3]
3. http://www.worldobesity.org/aboutobesity/resources/world-map-obesity
Fifth risk for global deaths [4]
Metabolic syndrome: insulin-resistance, type 2 diabetes, dyslipidemia,
arterial hypertension
External environmental (accounts for 60%-70%) and genetic factors
(accounts for 30%-40%) [5]
4. http://www.who.int
5. Central nervous system control of food intake [Review]. Nature 2000;404:661–71.
• Definition
• Body mass regulation
Orexigenic and anorexigenic peptides production
• Obesity as heritable disorder
Monogenic and polygenic forms of obesity
SNS activation
hypothalamus
BAT thermogenesis
NPY
AGRP
Y1R
MC4R
POMC
leptin
α-MSH
CART
adipocyte
food intake
Increased energy
expenditure
• Definition
• Body mass regulation
Orexigenic and anorexigenic peptides production
• Obesity as heritable disorder
Monogenic and polygenic forms of obesity
 Monogenic obesity
Complete inactivation of these genes (POMC, MC4R, LEP, LEPR) invariably results in
severe hyperphagia and fully penetrant obesity (rare), whereas heterozygous
carriers of deleterius mutations present a milder form of obesity.
 Polygenic obesity
Genome-wide association studies identify the SNPs that occur more frequently in
diseased people.
Variation in the intron 1 of Fat mass and obesity associated (FTO) gene is identified
as the major contributor to polygenic obesity.
Several of the likely causal obesity genes identified through GWAS studies (FTO,
MC4R, POMC, BDNF) are highly expressed or known to act in the central nervous
system, indicating a key role for central regulation of food intake in obesity
susceptibility in line with monogenic forms of human obesity. [6]
6. Current Genomics, 2011, 12, 155-158