1. 瘦體素 Obesity and Leptin WT ob (db) 2010 Albert Lasker award
Douglas Coleman
Jeffrey M. Friedman 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.

2. 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)
(feedback regulation)
ob lacks a blood-borne satiety factor (leptin)
Coleman (2010) Nature Med. 16:

3. Nature 372: (December 1, 1994)

4. Science 269: (July 28, 1995)
reduced food intake
increased energy expenditure
weight loss.

5. Expression of ob Gene in Adipose Cells REGULATION BY INSULIN*
Proc. Natl. Acad. Sci. USA 92: , September 1995
Expression of ob Gene in Adipose Cells
REGULATION BY INSULIN*
JBC 271:2365–2368, February 1996

7. Leptin binding to mouse brain slice
Choroid plexus
Expression cloning:
Choroid plexus => mRNA => cDNA => expression in pools
=> Binding to murine AP-OB fusion protein

8. Cell, Vol. 84, 491–495, February 9, 1996

9. J. Clin. Invest. 108:1113–1121 (2001)

10. Multiple receptor isoforms
Ahima & Flier (2000) Annu. Rev. Physiol. 62:413–37

11. Genome Res : 5-12

12. Congenital leptin deficiency is associated with severe early-onset obesity in humans
Montague et al (1997) Nature 387:
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.

13. A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction
Clement et al (1998) Nature 392:
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.

14. Nature 395: (1998)

16. Biological response to high versus low leptin levels

17. Pathogenesis of obesity

18. Regulation of leptin expression and the development of obesity

19. Therapy by leptin Most patient are resistant to leptin treatment !
Farooqi and O’Rahilly (2006) Endocr. Rev. 27:

20. Ahima & Flier (2000) Annu. Rev. Physiol. 62:413–37

21. Mechanism of leptin signaling

24. Das (2010) Nutrition 26 :459–473

25. Ruth Harris
Insulin secretion
Growth hormone
Stress
Reproduction