Was there really a monster in Jake’s
stomach??
Q: What is Leptin?????
Leptin (from Greek λεπτός leptos, "thin"), the
"satiety hormone“
• A Protein.
• a hormone made by adipose cells that
helps to regulate energy balance by
inhibiting hunger
• is opposed by the actions of the
hormone ghrelin, the "hunger hormone".
• Both hormones act on receptors in
the hypothalamus to regulate appetite in
order to achieve energy homeostasis
• 1994, Friedman's laboratory reported the
identification of the gene.
• In 1995, Jose F. Caro's laboratory provided
evidence that the mutations in the mouse ob
gene did not occur in humans.
• Leptin was the first fat cell-derived hormone
(adipokine) to be discovered.
• Subsequent studies in 1995 confirmed that it
is expressed in the hypothalamus, a region of
the brain known to regulate the sensation of
hunger and body weight.
Physiological effects of Leptin
Regulation of food intake ,energy expenditure
and body weight .
Reproductive function .
Directly act on the cells of liver and muscles.
Role of leptin in regulation of food
intake and body weight
Decrease hunger and food consumption.
Food intake linked to its ability to regulate the
neuroendocrine system .
Role of leptin in reproduction
Fertility influenced by stored body fat
Leptin signals the onset of puberty .
Regulates hypothalamic- pituitary –
ovarian function .
Thermogenesis?
 Non-shivering thermogenesis is regulated
mainly by thyroid hormone and
the sympathetic nervous system. Some
hormones, such
as norepinephrine and leptin, may stimulate
thermogenesis by activating the
sympathetic nervous system. Rising insulin
levels after eating may be responsible for
diet-induced thermogenesis .
Obesity
 Main focus of leptin research.
 Dramatic effects on obesity in mice.
 In human a body mass index over 27.3 for man & 27.8
for women.
 Hypothalamic insensitivity to leptin – fundamental
mechanism of obesity.
Leptin resistance
Mutation of the gene for leptin receptors in the brain
Post receptor abnormalities in leptin signal
transduction
Impaired leptin transport across blood- brain barrier
What about humans:
Mutation in gene for leptin or its receptor are rarely
found in obese people
High blood conc. leptin indicates leptin resistance
Extreme obesity in 5 members of two families that are
homozygous for mutation in their leptin gene –like
mice.
Recombinant human leptin available.
The 16 september 1999 issue the New England Journal
of Medicine reports- 9 year old girl homozygous for
frame shift mutation leptin gene.
Leptin research results
 Weight lost with mutated ob gene
 More obese less sensitive to high level of leptin