瘦體素. Obesity and Leptin. 2010 Albert Lasker award. Jeffrey M. Friedman. Douglas Coleman. WT. ob ( db ). For the discovery of leptin, a hormone that regulates appetite and body weight—a breakthrough that opened obesity research to molecular exploration.
Obesity and Leptin
2010 Albert Lasker award
Jeffrey M. Friedman
For the discovery of leptin, a hormone that regulates appetite and body weight—a breakthrough that opened obesity research to molecular exploration.
Effects of parabiosis of obese with diabetes and normal mice
Coleman (1973) Diabetologia 9:294-8
db overproduce a blood-borne satiety factor, but un-responsive
(defect in leptin receptor)
ob lacks a blood-borne satiety factor (leptin)
Coleman (2010) Nature Med. 16:1097-1099
Proc. Natl. Acad. Sci. USA 92: 9034-9037, September 1995
Expression of ob Gene in Adipose Cells
REGULATION BY INSULIN*
JBC 271:2365–2368, February 1996
Choroid plexus => mRNA => cDNA => expression in pools
=> Binding to murine AP-OB fusion protein
Ahima & Flier (2000) Annu. Rev. Physiol. 62:413–37
Congenital leptin deficiency is associated with severe early-onset obesity in humans
Montague et al (1997) Nature 387:903-908
We have examined two severely obese children who are members of the same highly consanguineous pedigree. Their serum leptin levels were very low despite their markedly elevated fat mass and, in both, a homozygous frame-shift mutation involving the deletion of a single guanine nucleotide in codon 133 of the gene for leptin was found.
A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction
Clement et al (1998) Nature 392: 398-401
Here we describe a homozygous mutation in the human leptin receptor gene that results in a truncated leptin receptor lacking both the transmembrane and the intracellular domains. In addition to their early-onset morbid obesity, patients homozygous for this mutation have no pubertal development and their secretion of growth hormone and thyrotropin is reduced.
Nature 395:763-770 (1998) and pituitary dysfunction
Biological response to high versus low leptin levels and pituitary dysfunction
Pathogenesis of obesity and pituitary dysfunction
Therapy by leptin obesity
Most patient are resistant to leptin treatment !
Farooqi and O’Rahilly (2006) Endocr. Rev. 27:710-718
Ahima & Flier (2000) obesityAnnu. Rev. Physiol. 62:413–37
Mechanism of leptin signaling obesity
Das (2010) Nutrition 26 :459–473 obesity
Ruth Harris obesity