iBet uBet web content aggregator. Adding the entire web to your favor.
iBet uBet web content aggregator. Adding the entire web to your favor.



Link to original content: http://pubmed.ncbi.nlm.nih.gov/15070752/
Phenotypic effects of leptin replacement on morbid obesity, diabetes mellitus, hypogonadism, and behavior in leptin-deficient adults - PubMed Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2004 Mar 30;101(13):4531-6.
doi: 10.1073/pnas.0308767101. Epub 2004 Mar 9.

Phenotypic effects of leptin replacement on morbid obesity, diabetes mellitus, hypogonadism, and behavior in leptin-deficient adults

Julio Licinio  1 , Sinan Caglayan, Metin Ozata, Bulent O Yildiz, Patricia B de Miranda, Fiona O'Kirwan, Robert Whitby, Liyin Liang, Pinchas Cohen, Shalender Bhasin, Ronald M Krauss, Johannes D Veldhuis, Anthony J Wagner, Alex M DePaoli, Samuel M McCann, Ma-Li Wong
Affiliations

Phenotypic effects of leptin replacement on morbid obesity, diabetes mellitus, hypogonadism, and behavior in leptin-deficient adults

Julio Licinio et al. Proc Natl Acad Sci U S A. .

Abstract

Genetic mutations in the leptin pathway can be a cause of human obesity. It is still unknown whether leptin can be effective in the treatment of fully established morbid obesity and its endocrine and metabolic consequences in adults. To test the hypothesis that leptin has a key role in metabolic and endocrine regulation in adults, we examined the effects of human leptin replacement in the only three adults identified to date who have genetically based leptin deficiency. We treated these three morbidly obese homozygous leptin-deficient adult patients with recombinant human leptin at low, physiological replacement doses in the range of 0.01-0.04 mg/kg for 18 months. Patients were hypogonadal, and one of them also had type 2 diabetes mellitus. We chose the doses of recombinant methionyl human leptin that would achieve normal leptin concentrations and administered them daily in the evening to model the normal circadian variation in endogenous leptin. The mean body mass index dropped from 51.2 +/- 2.5 (mean +/- SEM) at baseline to 26.9 +/- 2.1 kg/m2 after 18 months of treatment, mainly because of loss of fat mass. We document here that leptin replacement therapy in leptin-deficient adults with established morbid obesity results in profound weight loss, increased physical activity, changes in endocrine function and metabolism, including resolution of type 2 diabetes mellitus and hypogonadism, and beneficial effects on ingestive and noningestive behavior. These results highlight the role of the leptin pathway in adults with key effects on the regulation of body weight, gonadal function, and behavior.

PubMed Disclaimer

Figures

Fig. 1.
Fig. 1.
Patients are shown here at baseline and after leptin replacement. The older female patient (patient C) is on the left, and the younger female patient (patient B) is next to her. The male patient (patient A) is on the far right. For comparison purposes, two research nurses whose weights have been stable during this period are shown in the center. Patients' faces have been blurred to maintain confidentiality.
Fig. 2.
Fig. 2.
Effects of leptin replacement in adults. (a) Effects of r-metHuLeptin on weight in three leptin-deficient adults. Arrow indicates the start of r-metHuLeptin therapy. (b) Effects of r-metHuLeptin on energy intake in leptin-deficient adults. (c) Dose of s.c. r-metHuLeptin used in the three leptin-deficient adults.
Fig. 3.
Fig. 3.
Levels of 24-h physical activity measured in patient C during the course of leptin replacement. Representative days at baseline are shown in a and at 12 months after leptin in b.
Fig. 4.
Fig. 4.
Measurements of intensively collected samples of plasma hormone concentrations over the course of 24 h in the male patient, studied at baseline before and after 6 months daily leptin replacement by s.c. injection in the evening (arrow shows time of daily leptin injection). Each time series has 207 samples collected every 7 min, after 2 days of acclimatization in the research suite; meals were standardized.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Friedman, J. M. (2000) Nature 404, 632–634. - PubMed
    1. Kopelman, P. G. (2000) Nature 404, 635–643. - PubMed
    1. Zimmet, P., Alberti, K. G. & Shaw, J. (2001) Nature 414, 782–787. - PubMed
    1. Zhang, Y., Proenca, R., Maffei, M., Barone, M., Leopold, L. & Friedman, J. M. (1994) Nature 372, 425–432. - PubMed
    1. Farooqi, I. S., Keogh, J. M., Kamath, S., Jones, S., Gibson, W. T., Trussell, R., Jebb, S. A., Lip, G. Y. & O'Rahilly, S. (2001) Nature 414, 34–35. - PubMed

Publication types

Grants and funding