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Christos S Mantzoros - One of the best experts on this subject based on the ideXlab platform.

  • Leptin therapy in women with hypothalamic amenorrhea
    2015
    Co-Authors: Sharon H Chou, Christos S Mantzoros
    Abstract:

    Hypothalamic amenorrhea is caused by dysfunction of the hypothalamic–pituitary–gonadal axis associated with chronic energy deficiency from excessive exercise, psychological stress, or insufficient nutritional intake. In addition to amenorrhea, these women are also noted to have abnormalities in other neuroendocrine axes (e.g., cortisol excess, decreased thyroid hormones, growth hormone resistance), low bone turnover and bone mineral density, and low lymphocyte counts. HypoLeptinemia in these women has been proposed to signal a state of energy deficiency and set off these energy-conserving processes. In the context of two clinical trials studying the effects of Recombinant Leptin in women with HA, Leptin administration in replacement doses has been shown to restore reproductive function, decrease cortisol levels, increase triiodothyronine levels, increase insulin-growth factor-1 levels, improve bone mineral density, and increase CD4+ and CD8+ T-cell counts. If circulating Leptin reaches supraphysiological levels in response to Leptin administration, loss of weight and fat mass ensues; this is reversible however by decreasing the dose to achieve physiological levels. The potential use of Leptin in HA needs to be further studied.

  • Leptin therapy alters appetite and neural responses to food stimuli in brain areas of Leptin sensitive subjects without altering brain structure
    The Journal of Clinical Endocrinology and Metabolism, 2014
    Co-Authors: Olivia M Farr, Mary Brinkoetter, Christina G. Fiorenza, Panagiotis Papageorgiou, Florencia Ziemke, Bangbon Koo, Rafael Rojas, Christos S Mantzoros
    Abstract:

    Context: Leptin is a key regulator of energy intake and expenditure. Individuals with congenital Leptin deficiency demonstrate structural and functional brain changes when given Leptin. However, whether acquired Leptin deficiency may operate similarly is unclear. Objective: We set out to determine whether the brains of individuals with acquired Leptin deficiency may react to Leptin in a similar manner. Design: We used functional magnetic resonance imaging before and after short- and long-term metreLeptin treatment in three Leptin-sensitive patients with acquired hypoLeptinemia. Nine healthy women were scanned as normoLeptinemic controls. Setting: The setting was an academic medical center. Patients or Other Participants: The participants were 3 hypoLeptinemic women and nine normoLeptinemic, matched women. Interventions: We used metreLeptin, Recombinant Leptin, therapy for 24 weeks in hypoLeptinemic women only. Main Outcome Measure: We measured neural changes in response to viewing food as compared to nonf...

  • the effect of Leptin replacement on parathyroid hormone rankl osteoprotegerin axis and wnt inhibitors in young women with hypothalamic amenorrhea
    The Journal of Clinical Endocrinology and Metabolism, 2014
    Co-Authors: Stergios A Polyzos, Sharon H Chou, Christos S Mantzoros, Athanasios D Anastasilakis
    Abstract:

    Context: Recombinant Leptin (metreLeptin) treatment restores bone mineral density in women with hypothalamic amenorrhea (HA), a condition characterized by hypoLeptinemia, which has adverse impact on bone health. Objective: The objective of the study was to investigate how metreLeptin exerts its positive effect on bone metabolism in humans. Design: This was a randomized, double-blinded, placebo-controlled study. Setting: The study was conducted at Beth Israel Deaconess Medical Center (Boston, Massachusetts). Patients and Interventions: Women (n = 18) with HA and hypoLeptinemia for at least 6 months were randomized to receive either metreLeptin or placebo for 36 weeks. Serum samples were obtained at baseline and 12, 24, and 36 weeks of treatment. Main Outcome Measures: Circulating levels of Leptin, intact PTH (iPTH), receptor activator of nuclear factor-κB ligand (RANKL), osteoprotegerin (OPG), sclerostin, dickkopf-1, and fibroblast growth factor-23. Results: MetreLeptin administration significantly increas...

  • Leptin is an effective treatment for hypothalamic amenorrhea
    Proceedings of the National Academy of Sciences of the United States of America, 2011
    Co-Authors: Sharon H Chou, John P Chamberland, Rianna Stefanakis, Huizhi Gong, Kalliopi M Arampatzi, Mary Brinkoetter, Giuseppe Matarese, Christos S Mantzoros
    Abstract:

    Hypothalamic amenorrhea (HA) is associated with dysfunction of the hypothalamic-pituitary-peripheral endocrine axes, leading to infertility and bone loss, and usually is caused by chronic energy deficiency secondary to strenuous exercise and/or decreased food intake. Energy deficiency also leads to hypoLeptinemia, which has been proposed, on the basis of observational studies as well as an open-label study, to mediate the neuroendocrine abnormalities associated with this condition. To prove definitively a causal role of Leptin in the pathogenesis of HA, we performed a randomized, double-blinded, placebo-controlled trial of human Recombinant Leptin (metreLeptin) in replacement doses over 36 wk in women with HA. We assessed its effects on reproductive outcomes, neuroendocrine function, and bone metabolism. Leptin replacement resulted in recovery of menstruation and corrected the abnormalities in the gonadal, thyroid, growth hormone, and adrenal axes. We also demonstrated changes in markers of bone metabolism suggestive of bone formation, but no changes in bone mineral density were detected over the short duration of this study. If these data are confirmed, metreLeptin administration in replacement doses to normalize circulating Leptin levels may prove to be a safe and effective therapy for women with HA.

  • Recombinant human Leptin in women with hypothalamic amenorrhea
    The New England Journal of Medicine, 2004
    Co-Authors: Corrine Kolka Welt, Robyn Murphy, Aspasia Karalis, P.c. Smith, Alex M Depaoli, Jean L Chan, John Bullen, Christos S Mantzoros
    Abstract:

    Background Disruptions in hypothalamic–gonadal and other endocrine axes due to energy deficits are associated with low levels of the adipocyte-secreted hormone Leptin and may result in hypothalamic amenorrhea. We hypothesized that exogenous Recombinant Leptin replacement would improve reproductive and neuroendocrine function in women with hypothalamic amenorrhea. Methods Eight women with hypothalamic amenorrhea due to strenuous exercise or low weight were studied for one month before receiving Recombinant human Leptin and then while receiving treatment for up to three months. Six control subjects with hypothalamic amenorrhea received no treatment and were studied for a mean (±SD) of 8.5±8.1 months. Results Luteinizing hormone (LH) pulsatility, body weight, ovarian variables, and hormone levels did not change significantly over time in the controls and during a one-month control period before Recombinant Leptin therapy in the treated subjects. In contrast, Recombinant Leptin treatment increased mean LH lev...

Wim H M Saris - One of the best experts on this subject based on the ideXlab platform.

  • Effects of very low calorie diet induced body weight loss with or without human pegylated Recombinant Leptin treatment on changes in ghrelin and adiponectin concentrations.
    Physiology & Behavior, 2007
    Co-Authors: Manuela P G M Lejeune, Chris J Hukshorn, Wim H M Saris, Margriet S Westerterp-plantenga
    Abstract:

    Abstract The aim of the study was to investigate the effects of energy restriction with or without pegylated Recombinant Leptin (PEG-Leptin) treatment on ghrelin, adiponectin, insulin and glucose concentrations. A randomized double-blind placebo-controlled trial was performed in 24 moderately overweight/obese men. PEG-Leptin or placebo was administered weekly for 6 weeks, combined with a restricted energy intake of 2.1 MJ/d. At days 1, 25, and 46 a blood sample was taken and body-weight (BW) was measured. Days 1–25 was named phase 1, and days 25–46 phase 2. During phase 1 the rate of BW loss was significantly higher in the PEG-Leptin compared to the placebo group (0.38 ± 0.07 vs 0.32 ± 0.06 kg/d, p  Initial BW loss due to a considerable negative EB induced decreased ghrelin, adiponectin, insulin and glucose levels. However, when EB became less negative and the rate of BW loss decreased, these changes were reversed for adiponectin and ghrelin. The PEG-Leptin injections did not have an effect on the changes in insulin, glucose and adiponectin, but had an effect on the changes in ghrelin concentrations.

  • the effect of pegylated human Recombinant Leptin peg ob on neuroendocrine adaptations to semi starvation in overweight men
    European Journal of Endocrinology, 2003
    Co-Authors: Chris J Hukshorn, Margriet S Westerterpplantenga, Paul P C A Menheere, Wim H M Saris
    Abstract:

    Objective: Starvation induces a complex neuroendocrine response in humans thought to have evolved to defend against reduced energy intake. The drop in Leptin levels observed during fasting has been implicated as a factor that triggers this adaptive response. To explore this hypothesis, we executed a randomized, double-blind, placebo-controlled study to investigate whether elevated Leptin levels using long-acting pegylated human Recombinant Leptin (PEG-OB) influenced the neuroendocrine responses to semi-starvation in human subjects. Design: Twenty-four overweight male subjects (mean^S.E.M.; 34.8^1.3 yrs; 28.8^0.5 kg/m 2 ) were prescribed a very low energy diet (2.1 MJ/day) to induce a state of semi-starvation for the next 46 days. In addition, all subjects received a weekly treatment of 80 mg PEG-OB or matching placebo. Hormone measurements were performed throughout the study period and included 5-h frequent hormone samplings and 24-h urine collections. Results: Weekly subcutaneous administration of PEG-OB led to significant additional weight loss (2.8 kg) but it did not reverse the fasting-induced changes in the thyroid, corticotropic, somatotropic axes and sympathetic nervous system activity. However, after adjustment for weight loss, the drop in mean luteinizing hormone levels was attenuated in the PEG-OB group compared with the placebo group. Conclusions: These results suggest that a reduced level of Leptin accompanying food restriction might be a component of the fasting-induced neuroendocrine inhibition of the human reproductive axis.

  • pegylated human Recombinant Leptin peg ob causes additional weight loss in severely energy restricted overweight men
    The American Journal of Clinical Nutrition, 2003
    Co-Authors: Chris J Hukshorn, Margriet S Westerterpplantenga, Wim H M Saris
    Abstract:

    Pegylated human Recombinant Leptin (PEG-OB) causes additional weight loss in severely energy-restricted, overweight men. Hukshorn CJ, Westerterp-Plantenga MS, Saris WH. Nutrition and Toxicology Research Institute Maastricht, Department of Human Biology, Maastricht University, Maastricht, Netherlands. c.hukshorn@hb.unimaas.nl BACKGROUND: Increasing evidence suggests that falling Leptin concentrations observed during fasting act as a peripheral signal of starvation, which serves to conserve energy in the face of limited reserves. An extension of this hypothesis is that exogenous Leptin should affect energy regulation during severe energy restriction. OBJECTIVE: To explore this hypothesis, we assessed whether elevated Leptin concentrations achieved with the use of long-acting pegylated human Recombinant Leptin [polyethylene glycol-OB protein (PEG-OB)] affected weight loss and changes in body composition, energy expenditure, appetite, and metabolic variables during semistarvation in healthy overweight men. DESIGN: A randomized, double-blind, placebo-controlled study was executed in overweight men with a mean (+/- SEM) age of 34.8 +/- 1.3 y and body mass index (in kg/m2) of 28.8 +/- 0.5. All subjects received weekly treatment with 80 mg PEG-OB (n = 12) or matching placebo (n = 10) for 46 d while their energy intake was reduced to 2.1 MJ/d by means of a very-low-energy diet. Body composition (hydrodensitometry and deuterium dilution), energy expenditure (ventilated hood), and appetite (visual analogue scales) were evaluated at the start and the end of the study. Metabolic variables were measured throughout the study period. RESULTS: Compared with placebo treatment, treatment with PEG-OB led to significant (P < 0.03) additional weight loss (14.6 +/- 0.8 compared with 11.8 +/- 0.9 kg) and a reduction in appetite (P < 0.05) after 46 d, but the 2 treatment groups did not differ significantly in changes in body composition, energy expenditure, and metabolic variables. CONCLUSION: Our observations support the hypothesis that the decrease in Leptin concentrations during starvation increases appetite in humans

  • effect of dietary restraint during and following pegylated Recombinant Leptin peg ob treatment of overweight men
    International Journal of Obesity, 2003
    Co-Authors: M P G M Lejeune, Chris J Hukshorn, Wim H M Saris, Margriet S Westerterpplantenga
    Abstract:

    OBJECTIVE: To examine the effect of dietary restraint during and following pegylated Recombinant Leptin (PEG-OB protein) treatment in overweight men. DESIGN: A randomized double-blind placebo-controlled trial in 24 overweight men (BMI: 28.8±0.3 kg/m2; age: 34.8±0.9 y). PEG-OB protein (80 mg) or placebo was administered subcutaneously weekly for 6 weeks, combined with a 2.1 MJ/day energy restriction program. Dietary restraint was determined by the Three-Factor Eating Questionnaire before and after treatment, and after 8 weeks follow-up. RESULTS: During treatment dietary restraint increased, and general hunger, resting energy expenditure and respiratory quotient decreased similarly in the PEG-OB and the placebo group. With PEG-OB treatment, additional weight loss (P<0.03) was observed. During 8 weeks follow-up, body weight increase was larger in the PEG-OB group compared to placebo (P<0.05), and body weight regain was faster. Body weight regain was inversely correlated with the increase in cognitive dietary restraint during treatment (PEG-OB group: r2=0.49, P<0.02; placebo group: r2=0.60, P=0.01). CONCLUSION: Although treatment with PEG-OB protein led to a greater body weight loss relative to placebo, weight maintenance thereafter was mainly supported by dietary restraint, which was more effective in the placebo-treated group, resulting in a slower regain of body weight.

Chris J Hukshorn - One of the best experts on this subject based on the ideXlab platform.

  • Effects of very low calorie diet induced body weight loss with or without human pegylated Recombinant Leptin treatment on changes in ghrelin and adiponectin concentrations.
    Physiology & Behavior, 2007
    Co-Authors: Manuela P G M Lejeune, Chris J Hukshorn, Wim H M Saris, Margriet S Westerterp-plantenga
    Abstract:

    Abstract The aim of the study was to investigate the effects of energy restriction with or without pegylated Recombinant Leptin (PEG-Leptin) treatment on ghrelin, adiponectin, insulin and glucose concentrations. A randomized double-blind placebo-controlled trial was performed in 24 moderately overweight/obese men. PEG-Leptin or placebo was administered weekly for 6 weeks, combined with a restricted energy intake of 2.1 MJ/d. At days 1, 25, and 46 a blood sample was taken and body-weight (BW) was measured. Days 1–25 was named phase 1, and days 25–46 phase 2. During phase 1 the rate of BW loss was significantly higher in the PEG-Leptin compared to the placebo group (0.38 ± 0.07 vs 0.32 ± 0.06 kg/d, p  Initial BW loss due to a considerable negative EB induced decreased ghrelin, adiponectin, insulin and glucose levels. However, when EB became less negative and the rate of BW loss decreased, these changes were reversed for adiponectin and ghrelin. The PEG-Leptin injections did not have an effect on the changes in insulin, glucose and adiponectin, but had an effect on the changes in ghrelin concentrations.

  • the effect of pegylated human Recombinant Leptin peg ob on neuroendocrine adaptations to semi starvation in overweight men
    European Journal of Endocrinology, 2003
    Co-Authors: Chris J Hukshorn, Margriet S Westerterpplantenga, Paul P C A Menheere, Wim H M Saris
    Abstract:

    Objective: Starvation induces a complex neuroendocrine response in humans thought to have evolved to defend against reduced energy intake. The drop in Leptin levels observed during fasting has been implicated as a factor that triggers this adaptive response. To explore this hypothesis, we executed a randomized, double-blind, placebo-controlled study to investigate whether elevated Leptin levels using long-acting pegylated human Recombinant Leptin (PEG-OB) influenced the neuroendocrine responses to semi-starvation in human subjects. Design: Twenty-four overweight male subjects (mean^S.E.M.; 34.8^1.3 yrs; 28.8^0.5 kg/m 2 ) were prescribed a very low energy diet (2.1 MJ/day) to induce a state of semi-starvation for the next 46 days. In addition, all subjects received a weekly treatment of 80 mg PEG-OB or matching placebo. Hormone measurements were performed throughout the study period and included 5-h frequent hormone samplings and 24-h urine collections. Results: Weekly subcutaneous administration of PEG-OB led to significant additional weight loss (2.8 kg) but it did not reverse the fasting-induced changes in the thyroid, corticotropic, somatotropic axes and sympathetic nervous system activity. However, after adjustment for weight loss, the drop in mean luteinizing hormone levels was attenuated in the PEG-OB group compared with the placebo group. Conclusions: These results suggest that a reduced level of Leptin accompanying food restriction might be a component of the fasting-induced neuroendocrine inhibition of the human reproductive axis.

  • pegylated human Recombinant Leptin peg ob causes additional weight loss in severely energy restricted overweight men
    The American Journal of Clinical Nutrition, 2003
    Co-Authors: Chris J Hukshorn, Margriet S Westerterpplantenga, Wim H M Saris
    Abstract:

    Pegylated human Recombinant Leptin (PEG-OB) causes additional weight loss in severely energy-restricted, overweight men. Hukshorn CJ, Westerterp-Plantenga MS, Saris WH. Nutrition and Toxicology Research Institute Maastricht, Department of Human Biology, Maastricht University, Maastricht, Netherlands. c.hukshorn@hb.unimaas.nl BACKGROUND: Increasing evidence suggests that falling Leptin concentrations observed during fasting act as a peripheral signal of starvation, which serves to conserve energy in the face of limited reserves. An extension of this hypothesis is that exogenous Leptin should affect energy regulation during severe energy restriction. OBJECTIVE: To explore this hypothesis, we assessed whether elevated Leptin concentrations achieved with the use of long-acting pegylated human Recombinant Leptin [polyethylene glycol-OB protein (PEG-OB)] affected weight loss and changes in body composition, energy expenditure, appetite, and metabolic variables during semistarvation in healthy overweight men. DESIGN: A randomized, double-blind, placebo-controlled study was executed in overweight men with a mean (+/- SEM) age of 34.8 +/- 1.3 y and body mass index (in kg/m2) of 28.8 +/- 0.5. All subjects received weekly treatment with 80 mg PEG-OB (n = 12) or matching placebo (n = 10) for 46 d while their energy intake was reduced to 2.1 MJ/d by means of a very-low-energy diet. Body composition (hydrodensitometry and deuterium dilution), energy expenditure (ventilated hood), and appetite (visual analogue scales) were evaluated at the start and the end of the study. Metabolic variables were measured throughout the study period. RESULTS: Compared with placebo treatment, treatment with PEG-OB led to significant (P < 0.03) additional weight loss (14.6 +/- 0.8 compared with 11.8 +/- 0.9 kg) and a reduction in appetite (P < 0.05) after 46 d, but the 2 treatment groups did not differ significantly in changes in body composition, energy expenditure, and metabolic variables. CONCLUSION: Our observations support the hypothesis that the decrease in Leptin concentrations during starvation increases appetite in humans

  • effect of dietary restraint during and following pegylated Recombinant Leptin peg ob treatment of overweight men
    International Journal of Obesity, 2003
    Co-Authors: M P G M Lejeune, Chris J Hukshorn, Wim H M Saris, Margriet S Westerterpplantenga
    Abstract:

    OBJECTIVE: To examine the effect of dietary restraint during and following pegylated Recombinant Leptin (PEG-OB protein) treatment in overweight men. DESIGN: A randomized double-blind placebo-controlled trial in 24 overweight men (BMI: 28.8±0.3 kg/m2; age: 34.8±0.9 y). PEG-OB protein (80 mg) or placebo was administered subcutaneously weekly for 6 weeks, combined with a 2.1 MJ/day energy restriction program. Dietary restraint was determined by the Three-Factor Eating Questionnaire before and after treatment, and after 8 weeks follow-up. RESULTS: During treatment dietary restraint increased, and general hunger, resting energy expenditure and respiratory quotient decreased similarly in the PEG-OB and the placebo group. With PEG-OB treatment, additional weight loss (P<0.03) was observed. During 8 weeks follow-up, body weight increase was larger in the PEG-OB group compared to placebo (P<0.05), and body weight regain was faster. Body weight regain was inversely correlated with the increase in cognitive dietary restraint during treatment (PEG-OB group: r2=0.49, P<0.02; placebo group: r2=0.60, P=0.01). CONCLUSION: Although treatment with PEG-OB protein led to a greater body weight loss relative to placebo, weight maintenance thereafter was mainly supported by dietary restraint, which was more effective in the placebo-treated group, resulting in a slower regain of body weight.

Alex M Depaoli - One of the best experts on this subject based on the ideXlab platform.

  • Long-term efficacy of Leptin replacement in patients with Dunnigan-type familial partial lipodystrophy
    Metabolism: clinical and experimental, 2007
    Co-Authors: Jean Y. Park, Alex M Depaoli, Elaine Cochran, Edward D Javor, Phillip Gorden
    Abstract:

    The Dunnigan-type familial partial lipodystrophy (FPLD) is characterized by a variable loss of fat from the extremities and trunk and excess subcutaneous fat in the chin and supraclavicular area. Associated metabolic abnormalities include hypoLeptinemia, insulin resistance, and dyslipidemia. Our goal was to observe changes in metabolic parameters for patients with FPLD on long-term Leptin replacement and to compare the metabolic characteristics seen in FPLD with those seen in generalized lipodystrophy (GL) from our previous studies. This was an open-label study of 6 patients with FPLD receiving maximal doses of oral antidiabetic and lipid-lowering medications at baseline. Recombinant Leptin was given through twice-daily subcutaneous injections at a maximal dose of 0.08 mg/kg per day over 12 months to simulate normal to high normal physiologic levels. Triglycerides were reduced by 65% at 4 months (749 ± 331 to 260 ± 58 mg/dL) and significantly reduced at 12 months for 5 patients (433 ± 125 to 247 ± 69 mg/dL; P = .03). Total cholesterol also decreased (280 ± 49 to 231 ± 41 mg/dL; P = .01). Insulin sensitivity and fasting glucose levels (190 ± 26 to 151 ± 15 mg/dL; P < .01) improved. Glucose tolerance and glycosylated hemoglobin levels (8.4% ± 0.6% to 8.0% ± 0.4%; P = .07) did not change. As shown in patients with GL, patients with FPLD have improvement in triglycerides, fasting glucose, and insulin sensitivity with Leptin replacement. In contrast to the patients with GL, the patients with FPLD are older, have higher Leptin levels, and notably lower insulin secretion for a similar degree of hyperglycemia. Low-dose Recombinant methionyl human Leptin for patients with FPLD has an important role in improving triglycerides, beyond that of available lipid-lowering agents. In improving glycemic control, normalization of glucose tolerance in hypoinsulinemic patients with FPLD requires insulin and Leptin therapy. This is the first study to examine the effects of long-term Leptin replacement in patients with FPLD.

  • Recombinant human Leptin in women with hypothalamic amenorrhea
    The New England Journal of Medicine, 2004
    Co-Authors: Corrine Kolka Welt, Robyn Murphy, Aspasia Karalis, P.c. Smith, Alex M Depaoli, Jean L Chan, John Bullen, Christos S Mantzoros
    Abstract:

    Background Disruptions in hypothalamic–gonadal and other endocrine axes due to energy deficits are associated with low levels of the adipocyte-secreted hormone Leptin and may result in hypothalamic amenorrhea. We hypothesized that exogenous Recombinant Leptin replacement would improve reproductive and neuroendocrine function in women with hypothalamic amenorrhea. Methods Eight women with hypothalamic amenorrhea due to strenuous exercise or low weight were studied for one month before receiving Recombinant human Leptin and then while receiving treatment for up to three months. Six control subjects with hypothalamic amenorrhea received no treatment and were studied for a mean (±SD) of 8.5±8.1 months. Results Luteinizing hormone (LH) pulsatility, body weight, ovarian variables, and hormone levels did not change significantly over time in the controls and during a one-month control period before Recombinant Leptin therapy in the treated subjects. In contrast, Recombinant Leptin treatment increased mean LH lev...

  • proteinuric nephropathy in acquired and congenital generalized lipodystrophy baseline characteristics and course during Recombinant Leptin therapy
    The Journal of Clinical Endocrinology and Metabolism, 2004
    Co-Authors: Edward D Javor, Emin Argun Oral, Alex M Depaoli, Elaine Cochran, Stephanie Ann Moran, Janice Ryan Young, Martin A Turman, Piers R Blackett, David B Savage, Stephen Orahilly
    Abstract:

    Generalized lipodystrophy is characterized by adipose tissue absence, hypoLeptinemia, hypertriglyceridemia, insulin resistance, diabetes, hepatomegaly, and nonalcoholic steatohepatitis. In the course of recruiting patients for treatment with Recombinant Leptin, we were struck by the frequency and severity of proteinuria. We evaluated 25 patients with generalized lipodystrophy. Eighteen were treated with Recombinant Leptin, and we have followed 15 on Leptin for 4-36 months. We followed renal parameters at baseline and during follow-up visits. Renal biopsies were performed as clinically indicated. At baseline, 22 of 25 patients (88%) had elevated urine albumin excretion (>30 mg/24 h), 15 (60%) had macroalbuminuria (>300 mg/24 h), and five (20%) had nephrotic-range proteinuria (>3500 mg/24 h). Twenty-three (92%) had elevated creatinine clearance (>125 ml/min.1.73 m(2)). Eleven of 15 patients (73%) treated with Recombinant Leptin exhibited reduction in proteinuria, associated with reduction of hyperfiltration. Four patients who did not improve are discussed individually. Renal biopsy findings were remarkable for focal segmental glomerulosclerosis in four patients, membranoproliferative glomerulonephritis in two patients, and diabetic nephropathy in one patient. In conclusion, generalized lipodystrophy is associated with proteinuria and unique renal pathologies, including focal segmental glomerulosclerosis and membranoproliferative glomerulonephritis. The majority treated with Recombinant Leptin demonstrated reduction in proteinuria and hyperfiltration.

  • Congenital Leptin Deficiency Due to Homozygosity for the Δ133G Mutation: Report of Another Case and Evaluation of Response to Four Years of Leptin Therapy
    The Journal of clinical endocrinology and metabolism, 2004
    Co-Authors: William T. Gibson, Alex M Depaoli, Elizabeth Lawrence, I. Sadaf Farooqi, Mary Moreau, Stephen O'rahilly, Rebecca Trussell
    Abstract:

    Congenital Leptin deficiency is a rare, but treatable, cause of severe early-onset obesity. To date, two United Kingdom families of Pakistani origin carrying a frameshift/premature stop mutation, c.398delG (Δ133G), and one Turkish family carrying a missense mutation, c.313C>T (Arg105Trp), have been described. Affected subjects are homozygotes and manifest severe obesity and hyperphagia accompanied by metabolic, neuroendocrine, and immune dysfunction. The effects of Recombinant Leptin therapy have been reported in three children with the Δ133G mutation, and in all cases this has led to a dramatic resolution of clinical and biochemical abnormalities. We now report a Canadian child, of Pakistani origin but unrelated to the previously reported subjects, presenting with severe hyperphagia and obesity, who was found to be homozygous for the Δ133G mutation. In this child, 4 yr of therapy with sc injections of Recombinant Leptin provided additional evidence for the sustained beneficial effects of Leptin replaceme...

  • effect of Leptin replacement on pituitary hormone regulation in patients with severe lipodystrophy
    The Journal of Clinical Endocrinology and Metabolism, 2002
    Co-Authors: Emin Argun Oral, Elaine Ruiz, Alex M Depaoli, Alexa Andewelt, Nancy G Sebring, Anthony J Wagner, Phillip Gorden
    Abstract:

    Leptin is important in regulating energy homeostasis. Severe lipodystrophy is associated with Leptin deficiency and insulin resistance, hypertriglyceridemia, and hepatic steatosis. Leptin deficiency is also associated with abnormalities of the pituitary hormones in rodent models and patients with congenital absence of Leptin. We inquired whether similar abnormalities are seen in patients with lipodystrophy and whether replacement of Leptin will make an impact on the regulation of pituitary hormones. Seven female patients (aged 15–42 yr, all diabetic) with lipodystrophy and serum Leptin levels less than 4 mg/liter were treated with Recombinant methionyl-human Leptin (Recombinant Leptin) in physiological doses in an open-labeled study. The following parameters were evaluated before and at 4 months of Leptin treatment: menstrual history, pelvic ultrasonogram, LHRH, TRH, and CRH tests. While on Recombinant Leptin, mean serum Leptin concentration increased from 1.3 ± 0.3 mg/liter to 11.1 ± 2.5 mg/liter. Only o...

Manuel Carrillo - One of the best experts on this subject based on the ideXlab platform.

  • action of Leptin on in vitro luteinizing hormone release in the european sea bass dicentrarchus labrax
    Biology of Reproduction, 2001
    Co-Authors: Pierre Peyon, Silvia Zanuy, Manuel Carrillo
    Abstract:

    The discovery of Leptin has sparked a rapidly growing number of publications concerning the role of Leptin in the regulation of body adiposity, feeding, and reproductive system in mammals. To date, there have been no reports on the presence of Leptinrelated peptide, and functional studies on the role of Leptin remain limited in fishes. We investigated the effect of mouse Recombinant Leptin on basal and sea bream (sb) GnRH-induced LH release from dispersed pituitary cells obtained from male European sea bass (Dicentrarchus labrax) at different stages of sexual development. The potential interaction of Leptin with the porcine neuropeptide Y (pNPY), known to play a dual role in feeding and reproduction in vertebrates, was also investigated. High doses of Leptin (10‐8 ‐10 26 M) and/or pNPY (0.1 and 1 nM) had different effects on LH release at various stages of sexual development. Porcine NPY alone was weakly effective on basal LH release, but it enhanced LH release induced by Leptin (1026 M) in late prepuberty but not in early postpuberty. Additive or inhibitory effects of Leptin were observed on sbGnRH-induced LH release depending on sbGnRH dose and stage of sexual development. The direct action of Leptin on LH release at the pituitary level in sea bass suggests that Leptin is a regulator of the reproductive system in fishes. anterior pituitary, fish, gonadotropin-releasing hormone, Leptin, luteinizing hormone, neuropeptide Y, puberty