1. Leptin
2. Introduction
The function of the OB gene which is also alternatively known as LEP, OB, OBS is to code for leptin (1). Human leptin displays 84% sequence identity with the mouse product (2) and is synthesized in utero (3). It is secreted by the placenta and white adipocytes (4) and its secretion is related to the metabolism of glucose (5). Levels of leptin in serum are gender-related with women having higher average levels than men (6). The OB gene is over-expressed in obese individuals (7, 8).
The leptin protein has several functions. Leptin regulates body weight by inducing the expenditure of energy and inhibiting the intake of food (9), regulates angiogenesis (9) and is involved in the healing of wounds (9). Leptin also regulates haematopoiesis (9), takes part in the immune response (9), is involved in inflammation (9), and is associated with differentiation of adipose cells and acts as a target for C/EBP-alpha (10, 11). In addition, leptin is linked to the onset of puberty in humans (12) and has been shown to enhance prostate growth and elevated levels may lead to prostate cancer (13).
Humans and rodents with deficiencies in the production of leptin due to mutations or other factors are prone to serious hereditary obesity, generalized lipodystrophy, morbid obesity with hypogonadism, and impaired T-cell immunity (14). Deficiencies in leptin production also lead to development of type 2 diabetes mellitus. Recombinant leptin can be used to treat congenital leptin deficiencies (15, 16, 17, 18).
3. References
1. Tartaglia, L. A., Dembski, M., Weng, X., Deng, N., Culpepper, J., Devos, R., Richards, G. J., Campfield, L. A., Clark, F. T., Deeds, J., Muir, C., Sanker, S., Moriarty, A., Moore, K. J., Smutko, J. S., Mays, G. G., Woolf, E. A., Monroe, C. A., Tepper, R. I. Identification and expression cloning of a leptin receptor, OB-R. Cell 83: 1263-1271, 1995.
2. Masuzaki, H., Ogawa, Y., Isse, N., Satoh, N., Okazaki, T., Shigemoto, M., Mori, K., Tamura, N., Hosoda, K., Yoshimasa, Y., Jingami, H., Kawada, T., Nakao, K. Human obese gene expression: adipocyte-specific expression and regional differences in the adipose tissue. Diabetes 44: 855-858, 1995. [PubMed: 7789654, related citations] [Full Text: Pubget]
3. Koistinen, H. A., Koivisto, V. A., Andersson, S., Karonen, S.-L., Kontula, K., Oksanen, L., Teramo, K. A. Leptin concentration in cord blood correlates with intrauterine growth. J. Clin. Endocr. Metab. 82: 3328-3330, 1997.
4. Lonnqvist, F., Arner, P., Nordfors, L., Schalling, M. Overexpression of the obese (ob) gene in adipose tissue of human obese subjects. Nature Med. 1: 950-953, 1995
5. Masuzaki, H., Ogawa, Y., Sagawa, N., Hosoda, K., Matsumoto, T., Mise, H., Nishimura, H., Yoshimasa, Y., Tanaka, I., Mori, T., Nakao, K. Nonadipose tissue production of leptin: leptin as a novel placenta-derived hormone in humans. Nature Med. 3: 1029-1033, 1997.
6. Wellhoener, P., Fruehwald-Schultes, B., Kern, W., Dantz, D., Kerner, W., Born, J., Fehm, H. L., Peters, A. Glucose metabolism rather than insulin is a main determinant of leptin secretion in humans. J. Clin. Endocr. Metab. 85: 1267-1271, 2000.
7. Saad, M. F., Damani, S., Gingerich, R. L., Riad-Gabriel, M. G., Khan, A., Boyadjian, R., Jinagouda, S. D., El-Tawil, K., Rude, R. K., Kamdar, V. Sexual dimorphism in plasma leptin concentration. J. Clin. Endocr. Metab. 82: 579-584, 1997.
8. Hamilton, B. S., Paglia, D., Kwan, A. Y. M., Deitel, M. Increased obese mRNA expression in omental fat cells from massively obese humans. Nature Med. 1: 953-956, 1995.
9. Lonnqvist, F., Arner, P., Nordfors, L., Schalling, M. Overexpression of the obese (ob) gene in adipose tissue of human obese subjects. Nature Med. 1: 950-953, 1995.
10. He, Y., Chen, H., Quon, M. J., Reitman, M. The mouse ‘obese’ gene: genomic organization, promoter activity, and activation by CCAAT/enhancer-binding protein-alpha. J. Biol. Chem. 270: 28887-28891, 1995.
11. Miller, S. G., De Vos, P., Guerre-Millo, M., Wong, K., Hermann, T., Staels, B., Briggs, M. R., Auwerx, J. The adipocyte specific transcription factor C/EBP-alpha modulates human ob gene expression. Proc. Nat. Acad. Sci. 93: 5507-5511, 1996.
12. Mantzoros, C. S., Flier, J. S., Rogol, A. D. A longitudinal assessment of hormonal and physical alterations during normal puberty in boys. v. rising leptin levels may signal the onset of puberty. J. Clin. Endocr. Metab. 82: 1066-1070, 1997.
13. Stattin, P., Soderberg, S., Hallmans, G., Bylund, A., Kaaks, R., Stenman, U.-H., Bergh, A., Olsson, T. Leptin is associated with increased prostate cancer risk: a nested case-referent study. J. Clin. Endocr. Metab. 86: 1341-1345, 2001
14. Lord, G. M., Matarese, G., Howard, J. K., Baker, R. J., Bloom, S. R., Lechler, R. I. Leptin modulates the T-cell immune response and reverses starvation-induced immunosuppression. Nature 394: 897-901, 1998.
15. Farooqi, I. S., Jebb, S. A., Langmack, G., Lawrence, E., Cheetham, C. H., Prentice, A. M., Hughes, I. A., McCamish, M. A., O’Rahilly, S. Effects of recombinant leptin therapy in a child with congenital leptin deficiency. New Eng. J. Med. 341: 879-884, 1999.
16. Hukshorn, C. J., Saris, W. H. M., Westerterp-Plantenga, M. S., Farid, A. R., Smith, F. J., Campfield, L. A. Weekly subcutaneous pegylated recombinant native human leptin (PEG-OB) administration in obese men. J. Clin. Endocr. Metab. 85: 4003-4009, 2000.
17. Ebihara, K., Kusakabe, T., Hirata, M., Masuzaki, H., Miyanaga, F., Kobayashi, N., Tanaka, T., Chusho, H., Miyazawa, T., Hayashi, T., Hosoda, K., Ogawa, Y., DePaoli, A. M., Fukushima, M., Nakao, K. Efficacy and safety of leptin-replacement therapy and possible mechanisms of leptin actions in patients with generalized lipodystrophy. J. Clin. Endocr. Metab. 92: 532-541, 2007.
18. Farooqi, I. S., O’Rahilly, S. Is leptin an important physiological regulator of CRP? (Letter) Nature Med. 13: 16-17, 2007.
