Mutations in the human leptin and leptin receptor genes as models of serum leptin receptor regulation.
A part of serum Ob leptin, an adipocyte-secreted peptide, is bound to a soluble Ob receptor (sObR). Immunoreactive sObR was measured in 125 lean or obese control subjects (group 1), 18 individuals with a mutation in the leptin gene impairing leptin secretion (group 2), and 10 individuals with a mutation in the ObR gene, leading to production of a truncated ObR not anchored to cell membranes (group 3). In group 1, sObR levels were negatively correlated with age and BMI in children and with BMI in adults. sObR levels were also negatively correlated with leptin levels. Leptin binding activity and sObR levels coeluted in gel-filtration chromatography. In group 2, sObR levels did not differ from those in lean control subjects and were not correlated with BMI. A single peak was detected in chromatographic fractions. In group 3, sObR levels were high and positively correlated with BMI. Immunoreactive sObR coeluted with leptin binding activity. These data demonstrate that leptin is not needed for ObR gene expression, and they suggest that leptin plays a role in receptor downregulation because sObR levels are negatively correlated with leptin levels and BMI in control subjects, whereas sObR levels are not depressed in obese leptin-deficient or leptin receptor-deficient individuals.
Lahlou
Najiba
N
Hormone Biology, Saint-Vincent-de-Paul Hospital, Paris, France. najiba.lahlou@svp.ap-hop-paris.fr
Issad
Tarik
T
Lebouc
Yves
Y
Carel
Jean-Claude
JC
Camoin
Luc
L
Roger
Marc
M
Girard
Jean
J
D000293:Adolescent; D000328:Adult; D000368:Aged; D000375:Aging; D015992:Body Mass Index; D002352:Carrier Proteins / Q000097:blood* / Q000235:genetics*; D002648:Child; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D020738:Leptin / Q000172:deficiency / Q000235:genetics* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin
D002352:Carrier Proteins; C515448:LEPR protein, human; D020738:Leptin; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin