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 Friedman’s 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 “I’m full” Ob +/+ gene .

(2006) noted that the microbiome affects energy utilization in mice. 2009. A core gut microbiome in obese and lean twins Turnbaugh et al. colonization of germ-free mice with an “obese microbiome” results in significantly greater weight gain compared with “lean microbiome” colonization. Furthermore. twin studies Nature 457(7228): 480-484. adoptees. .HOW DO WE FIND THESE GENES? 2. Family.

ENERGY USE AND OBESE BACTERIA HEAT IN FECES .

MORE DIVERSE .IN HUMANS: LEANER.

RELATIVES DIVERSIFY SIMILARY .

MUTATIONS 1. Induced – chemicals. Spontaneous 2. viral infections . radiation.

Small Scale 1. Nonsense 2. Insertions/ Deletions Loss of function. Large Scale 1.EFFECTS OF MUTATIONS A. Chromosomal translocations 2. Amplifications or gene duplications/ deletions . gain of function. lethal mutations B. Point Mutations Silent. Missense.

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

controls appetite (satiety) .encodes for Leptin proteins that is secreted by white adipocytes .inhibit food intake .immune response.regulate energy expenditure . angiogenesis.LEP GENE LEP Gene .maintain constant adipose mass . hematopoeisis and wound healing .

leptin receptor .LEPR GENE .cytokine receptor .

LEP AND LEPR .

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