Leptin therapy

Leptin therapy has corrected obesity in a child with congenital leptin deficiency. In obese individuals, the presence of circulating high levels of leptin has been attributed to resistance or some other defect in the leptin receptors. This apparent paradox of high leptin levels associated with obesity is analogous to insulin resistance seen in type 2 diabetes mellitus. In general, in the vast majority of obese patients, the molecular defects remain unknown. Diet and exercise are the mainstays in the management of obesity. 

I. S. Farooqi, S. A. Jebb, G. Langmack, et al. Effects of recombinant leptin therapy in a child with congenital leptin deficiency. New England Journal of Medicine 341,879 (1999). 

A nuclear receptor that is a key transcription factor in adipocytes. It plays a critical role in the control of adipocyte differentiation and is involved in the regulation of the expression of specific adipokines, including leptin and adiponectin. It has anti-inflammatory actions and is the target of the thiazolidinedione drugs. The preintegration complex is a complex of retroviral DNA and proteins that translocates from the cytosol into the nucleus prior to integration. Gene Therapy... 

Poor sleep architecture and fragmented sleep secondary to OSA can cause excessive daytime sleepiness (EDS) and neu-rocognitive deficits. These sequelae can affect quality of life and work performance and may be linked to occupational and motor vehicle accidents. OSA is also associated with systemic disease such as hypertension, heart failure, and stroke.21-23 OSA is likely an independent risk factor for the development of hypertension.24 Further, when hypertension is present, it is often resistant to antihypertensive therapy. Fatal and non-fatal cardiovascular events are two- to threefold higher in male patients with severe OSA.25 OSA is associated with or aggravates biomarkers for cardiovascular disease, including C-reactive protein and leptin.26,27 Patients with sleep apnea often are obese and maybe predisposed to weight gain. Hence, obesity may further contribute to cardiovascular disease in this patient population. 

Bromel, T., Blum, W.F., Ziegler, A., Schulz, E., Bender, M., Fleis-chhaker, C., Remschmidt, H., Krleg, J.C., and Hebebrand, J. (1998) Serum leptin levels increase rapidly after initiation of clozapine therapy. Mol Psychiatry 3 76-80. 

Thrailkill KM, Fowlkes JL, Hyde JF, Litton JC. The effects of co-therapy with recombinant human insulin-like growth factor I and insulin on serum leptin levels in adolescents with type 1 diabetes mellitus. Pediatr Diabetes 2001 2(l) 25-9. 

The mechanisms involved have been assessed in 40 women with epilepsy evaluated before and after 1 year of therapy (1166). At the end of follow-up, 15 patients were obese and had higher serum leptin and insulin concentrations than patients who did not gain weight. The rise in serum leptin is consistent with that observed in other types of obesity. 

Verrotti A, Basciani F, Morresi S, de Martino M, Morgese G, Chiarelli F. Serum leptin changes in epileptic patients who gain weight after therapy with valproic acid. Neurology 1999 53(l) 230-2. 

Combined therapy with clozapine and fluvoxamine (n = 11) and clozapine monotherapy (n = 12) have been monitored before and during the first 6 weeks of medication (39). The co-administration of fluvoxamine attenuated and delayed the clozapine-induced increase in plasma concentrations of tumor necrosis factor-alpha, enhanced and accelerated the clozapine-induced increase in leptin plasma concentrations without a significant effect on clozapine-induced weight gain, and reduced granulocyte counts. 

Serum leptin levels increase rapidly after initiation of clozapine therapy. Mol Psychiatry 1998 3(l) 76-80. 

Lee, M. Shimabukuro, C. B. Newgard, and R. H. Unger, Beta-cell function in normal rats made chronically hyperlepti-nemic by adenovirus-leptin gene therapy. Diabetes, 1997, 46, 1276-1280. 

Chen G, Koyama K, Yuan X, Lee Y, Zhou YT, O Doherty R, et al. Disappearance of body fat in normal rats induced by adenovirus-mediated leptin gene therapy. Proc Natl Acad Sci USA 1996 93 14,795-14,799. 

ECT Electroconvulsive therapy ObRb Functional long leptin receptor... 

Gura, T. Obesity Sheds Its Secrets. Science 275, 751-753 (1997). [A Research News article on the role of the protein hormone leptin in obesity research and on the possibility of obesity therapies that might arise from this research.]... 

Markers associated with cardiovascular disease may alter during therapy with abacavir. For example, there was a 20% increase in C-reactive protein and interleukm-6 (IL-6) [90. However, in 11 patients there were no consistent changes in concentrations of D-dimers, IL-6, IL-8, TNFa, MCP-1, HGF, hs-CRP, leptin, or adiponectin [9T. ... 

Metabolism A prospective study foxmd increased body mass index, plasma insulin level, leptin, neuropeptide Y, and fasting insulinrglucose ratio in children taking VPA at 6 and 12 months after initiation of therapy [182 ]. Plasma ghrelin and adiponectin levels, lipid profiles, and carotid artery intima media thickness did not change significantly at the end of 6 and 12 months. 

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