Effects of Leptin Replacement on Risk Factors for Cardiovascular Disease in Genetically Leptin-deficient Subjects

Paz-Filho, Gilberto; Andrews, Debora L.; Esposito, Katherine; Erol, Halil; Delibaşı, Tuncay; Wong, Ma-Li; Licinio, Júlio

doi:10.1055/s-0028-1082037

Cited by 10 publications

(4 citation statements)

References 15 publications

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“…In a cohort of Turkish leptin-deficient patients, our 10-year experience of leptin replacement therapy showed that treatment leads to substantial effects on body composition, food intake and energy expenditure, lipid and glucose metabolism, sympathetic tone, and gonadal, adrenal, somatotropic and thyroid functions. Additional results also suggest that leptin has important roles on non-endocrine parameters, such as inflammation and coagulation (27), immunity (11,28), and brain structure and function (14,29-33). …”

Section: Discussionmentioning

confidence: 97%

Congenital leptin deficiency: diagnosis and effects of leptin replacement therapy

Paz-Filho

Mastronardi

Delibaşı

et al. 2010

Arq Bras Endocrinol Metab

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SUMMARY To describe our 10-year experience in treating leptin-deficient humans. Three adults and one boy presented with childhood-onset morbid obesity, hypogonadism and family history of obesity and early death. Serum leptin was inappropriately low. A recessive C105T leptin gene mutation was identified. Metabolic and endocrine assessments were conducted, before and while on and off leptin. The adults’ body mass index decreased from 51.2 ± 2.5 to 29.5 ± 2.8 kg/m2. Serum lipids normalized, insulin resistance decreased, and one of the initially diabetic females became normoglycemic. Hypogonadotropic hypogonadism was reversed, and other changes were observed in the adrenal, sympathetic, somatotropic and thyroid functions. Leptin replacement therapy reverses endocrine and metabolic alterations associated with leptin deficiency. Some of these results may be extrapolated to other diseases.

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Section: Discussionmentioning

confidence: 97%

Congenital leptin deficiency: diagnosis and effects of leptin replacement therapy

Paz-Filho

Mastronardi

Delibaşı

et al. 2010

Arq Bras Endocrinol Metab

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“…The changes in biomarkers of inflammation, coagulation, fibrinolysis and platelet aggregation did not follow a pattern after leptin replacement. However, leptin withdrawal determined changes in most of these biomarkers towards a decreased state of thrombogenesis and increased fibrinolysis (36). This suggests that the absence of leptin may protect against cardiovascular diseases, even in a morbidly obese state.…”

Section: Adrenal Sympathetic Tone and Biomarkers Of Cardiovascular Dmentioning

confidence: 98%

Ten years of leptin replacement therapy

2011

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SummaryLeptin is a pleiotropic cytokine-like hormone that is involved in the regulation of energy intake and expenditure, neuroendocrine function, immunity and lipid and glucose metabolism. The few humans with genetically based leptin deficiency provide a unique model to assess those effects. We have identified five Turkish patients (one male and two female adults; one boy and one girl) with congenital leptin deficiency due to a missense mutation in the leptin gene. Four of these patients were treated with physiological doses of recombinant methionyl human leptin. Body composition, brain structure and function, behaviour, immunity and endocrine and metabolic parameters were evaluated before and during treatment. Our results showed that leptin has peripheral, hypothalamic and extra-hypothalamic effects. Within the endocrine system, leptin regulates the circadian rhythms of cortisol, thyroidstimulating hormone, luteinizing hormone and follicle-stimulating hormone. In the brain, leptin controls energy balance and body weight, and plays a role on neurogenesis and brain function. Leptin is a key element of the adiposinsular axis, enhances immune response, and regulates inflammation, coagulation, fibrinolysis and platelet aggregation. Our 10-year experience in treating these unique patients provided valuable data on the peripheral and central effects of leptin. Those results can be taken into account for the development of leptin-based therapies for other diseases.

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“…Leptin has been implicated in inflammation, thrombogenesis and fibrinolysis (16)(17)(18), but it is yet unclear whether leptin is merely a biomarker of MetS and cardiovascular disease (16,19), or whether it is directly involved in the pathogenesis of those conditions (16,(20)(21)(22)(23)(24).…”

mentioning

confidence: 99%

Decrease in leptin production by the adipose tissue in obesity associated with severe metabolic syndrome

Paz-Filho

Volaco

Suplicy

et al. 2009

Arq Bras Endocrinol Metab

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Effects of Leptin Replacement on Risk Factors for Cardiovascular Disease in Genetically Leptin-deficient Subjects

Cited by 10 publications

References 15 publications

Congenital leptin deficiency: diagnosis and effects of leptin replacement therapy

Congenital leptin deficiency: diagnosis and effects of leptin replacement therapy

Ten years of leptin replacement therapy

Decrease in leptin production by the adipose tissue in obesity associated with severe metabolic syndrome

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