Leptin
A Potential Biomarker for Childhood Obesity ?
1
Prevalence of Childhood Obesity
Table 1.
Prevalence of Obese Children
(Ages 6 to 11) at the
Body Mass Index (BMI) >30
Table 2.
Prevalence of Obese Adolescents
(Ages 12 to 19) at the
Body Mass Index (BMI) >30
1999 to 2000
15.3%
1999 to 2000
15.5%
1988 to 1994
11%
1988 to 1994
11%
1976 to 1980
7%
1976 to 1980
5%
2
Centers for Disease Control (CDC)
Leptin and Obesity
Cause ?
Consequence ?
Intervention predictor/monitor ?
Prevention indicator ?
Novel biomarker ?
3
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).
4
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
5
Structure of Leptin
White adipose tissue
Hypothalamus
Pituitary
Skeletal muscle and bone
Arterial endothelium
Intestines
Fetus
Testes
Placenta
16kDa protein hormone
6
Action of Leptin
7
Leptin Receptor Isoforms
OB-Rf
8
Intracellular signaling by LRb
9
Leptin Deficiency leads to Obesity
10
11
The New England Journal of Medicine. 1999;341(12):879-884.
Correlation between plasma leptin levels
and BMI in adults
n =51
12
J Clin Endocrinol Metab, April 2002, 87(4):1708–1716
Correlation between plasma leptin levels
and % body fat in adults
13
J. Clin. Invest. 1996, 98(6):1277–1282
Correlation between serum leptin
levels and % fat in children
14
Endocrine Journal 1999, 46 (5), 703-709
Correlation between serum soluble leptin
receptor (sObR) levels and BMI in adults
15
Correlation between serum sObR levels and
BMI in children and adolescents
16
J Clin Endocrinol Metab, October 2002, 87(10):4587–4594
Free Leptin Index
Leptin/sObR
17
J Clin Endocrinol Metab, April 2003, 88(4):1730–173
Correlation between plasma leptin levels
and % body fat in adults
n=46
18
J. Clin. Invest. 1996, 98(6):1277–1282
free
bound
free
bound
19
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
20
Leptin and sObR: reason or consequence?
 sObR
 ObR
 Leptin
 Leptin
 sObR
21
Leptin, sObR levels respond to intervention
Physical training
Fasting/refeeding
Weight-losing Surgery
22
Plasma leptin levels after physical training in
children
23
Am J Clin Nutr 1999;69:388–94.
Leptin levels and exercise intervention in
children and/or adolescents
Clinical Biochemistry
39 (2006) 1047–1056
24
Free/Bound leptin levels during Fasting/Refeeding
25
J. Clin. Invest. 1996, 98(6):1277–1282
Leptin, sObR levels and weight-loss in children
26
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.
27
J Clin Endocrinol Metab, April 2002, 87(4):1708–1716
Plasma leptin, sObR, bound leptin levels after
weight-losing surgery
28
Baseline levels predict effects
of intervention
29
Baseline leptin levels predict the ability to lose body fat
30
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)
31
 leptin levels predict probability
of weight relapse
32
Diabetes Nutr Metab 2003;16(5-6):306-311.
% Boby Fat
Dual energy X-ray absorptiometry (DXA)
Bioelectric impedance
Skin-fold thickness
BMI
Diagnosis
Leptin/sObR?
Adipose tissue mass
Metabolic risk factors
Status of energy balance
Predict ability to lose weight?
Predict ability to gain/re-gain weight?
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