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Leptin A Potential Biomarker for Childhood Obesity ?. Prevalence of Childhood Obesity . Table 1. Prevalence of Obese Children (Ages 6 to 11) at the Body Mass Index (BMI) >30 1999 to 2000 15.3% 1988 to 1994 11% 1976 to 1980 7% .
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Leptin A Potential Biomarker for Childhood Obesity ?
Prevalence of Childhood Obesity Table 1. Prevalence of Obese Children (Ages 6 to 11) at the Body Mass Index (BMI) >30 1999 to 2000 15.3% 1988 to 1994 11% 1976 to 1980 7% Table 2. Prevalence of Obese Adolescents(Ages 12 to 19) at theBody Mass Index (BMI) >30 1999 to 2000 15.5% 1988 to 1994 11% 1976 to 1980 5% Centers for Disease Control (CDC)
Leptin and Obesity Cause ? Consequence ? Intervention predictor/monitor ? Prevention indicator ? Novel biomarker ?
What is a biomarker ? According to an expert working group convened by National Institutes of Health, a biomarker is defined as “a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathological processes, or pharmacological responses to a therapeutic intervention” (Clin Pharmacol Ther. 69, 89-95, 2001).
Use of a biomarker A tool fordiagnosing and stagingdisease An indicator of disease prognosis A tool forpredicting and monitoring clinical response to an intervention
Structure of Leptin White adipose tissue Hypothalamus Pituitary Skeletal muscle and bone Arterial endothelium Intestines Fetus Testes Placenta 16kDa protein hormone
OB-Rf Leptin Receptor Isoforms
Correlation between plasma leptin levels and BMI in adults n =51 J Clin Endocrinol Metab, April 2002, 87(4):1708–1716
Correlation between plasma leptin levels and % body fat in adults J. Clin. Invest. 1996, 98(6):1277–1282
Correlation between serum leptin levels and % fat in children Endocrine Journal 1999, 46 (5), 703-709
Correlation between serum soluble leptin receptor (sObR) levels and BMI in adults
Correlation between serum sObR levels and BMI in children and adolescents J Clin Endocrinol Metab, October 2002, 87(10):4587–4594
Free Leptin Index Leptin/sObR J Clin Endocrinol Metab, April 2003, 88(4):1730–173
Correlation between plasma leptin levels and % body fat in adults n=46 J. Clin. Invest. 1996, 98(6):1277–1282
free bound free bound J. Clin. Invest. 1996, 98(6):1277–1282
Leptin Resistance ? Defects in leptin access into the brain Defects in ObR Defects in ObR signaling Defects in pathways/neurons that mediate downstream leptin action
- - Leptin and sObR: reason or consequence? sObR ObR Leptin Leptin sObR
Leptin, sObR levels respond to intervention Physical training Fasting/refeeding Weight-losing Surgery
Plasma leptin levels after physical training in children Am J Clin Nutr 1999;69:388–94.
Leptin levels and exercise intervention in children and/or adolescents Clinical Biochemistry 39 (2006) 1047–1056
Free/Bound leptin levels during Fasting/Refeeding J. Clin. Invest. 1996, 98(6):1277–1282
Leptin, sObR levels and weight-loss in children International Journal of Obesity (2005) 29, 1230–1235.
Plasma sObR and leptin levels after weight-losing surgery in adults Plasma concentrations of leptin (open bars) and sLR (hatched bars) in ng/ml in lean and morbidly obese subjects(MO). For the morbidly obese group preoperative (gastric restrictive surgery) as well as 3, 6, and 12 months postoperative (3m, 6m and 12m) values are shown. Data are depicted as mean SEM. J Clin Endocrinol Metab, April 2002, 87(4):1708–1716
Plasma leptin, sObR, bound leptin levels after weight-losing surgery
Baseline leptin levels predict the ability to lose body fat Acta Pediatr 91: 132-135. 2002
Baseline leptin levels correlate with leptin Baseline leptin = 0.55 + 1.21(baseline fat mass) Change in leptin = 22.02 – 0.40(pretraining leptin)+ 3.74(change in total mass) Am J Clin Nutr 1999;69:388–94.
leptin levels predict probability of weight relapse Diabetes Nutr Metab 2003;16(5-6):306-311.
Dual energy X-ray absorptiometry (DXA) % Boby Fat Bioelectric impedance Skin-fold thickness Diagnosis BMI Adipose tissue mass Metabolic risk factors Status of energy balance Leptin/sObR? Predict ability to lose weight? Predict ability to gain/re-gain weight?