1 leptin a potential biomarker for childhood obesity ?
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Leptin
A Potential Biomarker for Childhood Obesity ?
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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%
Prevalence of Childhood Obesity
Centers for Disease Control (CDC)
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Cause ?
Consequence ?
Intervention predictor/monitor ?
Prevention indicator ?
Leptin and Obesity
Novel biomarker ?
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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).
What is a biomarker ?
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Use of a biomarker
A tool for diagnosing and staging disease
An indicator of disease prognosis
A tool for predicting and monitoring clinical response to an intervention
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16kDa protein hormone
White adipose tissueHypothalamusPituitarySkeletal muscle and boneArterial endotheliumIntestinesFetusTestesPlacenta
Structure of Leptin
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Action of Leptin
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Leptin Receptor Isoforms
OB-Rf
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Intracellular signaling by LRb
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Leptin Deficiency leads to Obesity
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The New England Journal of Medicine. 1999;341(12):879-884.
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n =51
J Clin Endocrinol Metab, April 2002, 87(4):1708–1716
Correlation between plasma leptin levels and BMI in adults
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J. Clin. Invest. 1996, 98(6):1277–1282
Correlation between plasma leptin levels and % body fat in adults
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Correlation between serum leptin levels and % fat in children
Endocrine Journal 1999, 46 (5), 703-709
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Correlation between serum soluble leptin receptor (sObR) levels and BMI in adults
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Correlation between serum sObR levels and BMI in children and adolescents
J Clin Endocrinol Metab, October 2002, 87(10):4587–4594
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Free Leptin Index
Leptin/sObR
J Clin Endocrinol Metab, April 2003, 88(4):1730–173
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J. Clin. Invest. 1996, 98(6):1277–1282
n=46
Correlation between plasma leptin levels and % body fat in adults
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bound
free bound
free
J. Clin. Invest. 1996, 98(6):1277–1282
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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
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Leptin and sObR: reason or consequence?
sObR ObR Leptin
Leptin sObR
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Leptin, sObR levels respond to intervention
Weight-losing Surgery
Fasting/refeeding
Physical training
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Plasma leptin levels after physical training in children
Am J Clin Nutr 1999;69:388–94.
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Leptin levels and exercise intervention in children and/or adolescents
Clinical Biochemistry 39 (2006) 1047–1056
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J. Clin. Invest. 1996, 98(6):1277–1282
Free/Bound leptin levels during Fasting/Refeeding
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Leptin, sObR levels and weight-loss in children
International Journal of Obesity (2005) 29, 1230–1235.
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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.
Plasma sObR and leptin levels after weight-losing surgery in adults
J Clin Endocrinol Metab, April 2002, 87(4):1708–1716
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Plasma leptin, sObR, bound leptin levels after weight-losing surgery
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Baseline levels predict effects of intervention
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Acta Pediatr 91: 132-135. 2002
Baseline leptin levels predict the ability to lose body fat
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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.
Baseline leptin levels correlate with leptin
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leptin levels predict probability of weight relapse
Diabetes Nutr Metab 2003;16(5-6):306-311.
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Diagnosis
Dual energy X-ray absorptiometry (DXA)
Bioelectric impedance
Skin-fold thickness
Leptin/sObR?
BMI
Adipose tissue massMetabolic risk factorsStatus of energy balance
Predict ability to lose weight?
% Boby Fat
Predict ability to gain/re-gain weight?