TARGETS FOR STUDY Drive to overeat (poor regulation of appetite and satiety) The tendency to be sedentary (physically inactive) A diminished ability to use dietary fats as fuel Enlarged, easily stimulated capacity to store body fat.

HOW DO WE FIND THESE GENES?1. Animal models Friedmans discovery of the leptin gene in yellow agouti mice 5 mutant strains are obese or have diabetes or tubby or fat because of a single gene mutation

Lacks the ob gene Product is Leptin tells brain Im full

Ob +/+ gene

HOW DO WE FIND THESE GENES?2. Family, adoptees, twin studies Nature 457(7228): 480-484, 2009. A core gut microbiome in obese and lean twins

Turnbaugh et al. (2006) noted that the microbiome affects energy utilization in mice. Furthermore, colonization of germ-free mice with an obese microbiome results in significantly greater weight gain compared with lean microbiome colonization.

ENERGY USE AND OBESE BACTERIA

HEAT IN FECES

IN HUMANS: LEANER, MORE DIVERSE

RELATIVES DIVERSIFY SIMILARY

MUTATIONS1. Spontaneous 2. Induced chemicals, radiation, viral infections

EFFECTS OF MUTATIONSA. Small Scale 1. Point Mutations Silent, Missense, Nonsense

2. Insertions/ DeletionsLoss of function, gain of function, lethal mutations B. Large Scale 1. Chromosomal translocations

2. Amplifications or gene duplications/ deletions

GENE OVERDOSE CAUSES EXTREME THINNESSScientists have discovered a genetic cause of extreme thinness for the first time, in a study published August 30,2011 in the journal Nature. The research shows that people with extra copies of certain genes are much more likely to be very skinny. In one in 2000 people, part of chromosome 16 is duplicated, making men 23 times and women five times more likely to be underweight. Last year, the same researchers discovered that people with a missing copy of these genes are 43 times more likely to be morbidly obese.

LEP GENELEP Gene - encodes for Leptin proteins that is secreted by white adipocytes - inhibit food intake

- controls appetite (satiety)- regulate energy expenditure - maintain constant adipose mass - immune response, angiogenesis, hematopoeisis and wound healing

LEPR GENE- leptin receptor - cytokine receptor

LEP AND LEPR