title: Intracellular leptin signaling following effective weight loss.
abstract: OBJECTIVE
  To investigate the effect of ex-vivo leptin treatment before and after weight loss on key-molecules of intracellular leptin signaling in peripheral blood mononuclear cells (PBMCs) of obese women.
  
  
  METHODS
  Five healthy obese women underwent a 12-week medical nutrition treatment aiming at inducing 10% weight loss. Isolated PBMCs at baseline, and at weeks 8 and 12 were treated with increasing leptin doses (0, 25 and 75 ng/ml) for 30 min. The phosphorylation of signal transducer and activator of transcription (STAT)3, extracellular-signal-regulated kinase (ERK), protein kinase B (Akt) and 5' adenosine monophosphate-activated protein kinase (AMPK) of PBMCs was analyzed using Western blotting.
  
  
  RESULTS
  Women lost 10 ± 1% and 13 ± 1% of weight at week 8 and 12, respectively. Circulating leptin and insulin significantly decreased from 39.5 ± 7.7 to 12.2 ± 2.4 ng/ml (p = 0.026) and from 13.0 ± 1.6 to 5.4 ± 0.9 μU/ml (p = 0.005) at week 12, respectively. In the ex vivo study, a significant decrease in STAT3 phosphorylation was observed in the control group after weight loss. Treatment of PBMCs with leptin 75 ng/ml increased significantly ERK, STAT3 and Akt phosphorylation, but no weight loss induced change was observed in response to leptin treatment ex vivo.
  
  
  CONCLUSIONS
  A 10%-15% weight loss decreases baseline STAT3 phosphorylation ex vivo, but does not alter the effect of increasing doses of leptin on the incremental intracellular phosphorylation of STAT3, ERK, Akt and AMPK. Supraphysiologic leptin doses (75 ng/ml) result in higher protein phosphorylation compared to either physiologic doses or no treatment, before and after weight loss.
authors.affiliation: Division of Endocrinology Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA; Section of Endocrinology, Boston VA Healthcare System, Harvard Medical School, Boston, MA.
authors.forename: Ayse
authors.initials: A
authors.lastname: Sahin-Efe
authors.affiliation: Division of Endocrinology Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA. Electronic address: stergios@endo.gr.
authors.forename: Stergios A
authors.initials: SA
authors.lastname: Polyzos
authors.affiliation: Division of Endocrinology Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
authors.forename: Fadime
authors.initials: F
authors.lastname: Dincer
authors.affiliation: Division of Endocrinology Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
authors.forename: Lesya
authors.initials: L
authors.lastname: Zaichenko
authors.affiliation: Division of Endocrinology Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
authors.forename: Rosemary
authors.initials: R
authors.lastname: McGovern
authors.affiliation: Division of Minimally Invasive Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Schneider
authors.affiliation: Division of Endocrinology Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA; Section of Endocrinology, Boston VA Healthcare System, Harvard Medical School, Boston, MA.
authors.forename: Christos S
authors.initials: CS
authors.lastname: Mantzoros
mesh_terms: D000328:Adult; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D006801:Humans; D020738:Leptin / Q000097:blood / Q000502:physiology / Q000627:therapeutic use*; D009765:Obesity / Q000188:drug therapy* / Q000503:physiopathology; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D054411:Receptors, Leptin / Q000097:blood; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D015431:Weight Loss / Q000502:physiology*
chemical_list: D020738:Leptin; D054411:Receptors, Leptin; D050796:STAT3 Transcription Factor; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Leptin; Leptin signaling; Obesity; STAT3; Weight loss