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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. Diabetes 51:1980-1985, 2002
CSF, cerebrospinal fluid.
Leptin exerts its biological activity through a membrane receptor (ObR) located in various tissues, including the brain (rev. in 1). The lack of leptin due to mutations in the leptin gene and the lack of functional leptin receptors result in early-onset obesity and various endocrine disturbances in both rodents and humans (2-5). In the leptin-deficient ob/ob mice as well as in human subjects harboring a mutation in the leptin gene that results in the absence of leptin production, parenteral administration of recombinant leptin reduces food intake and adiposity (6,7). These observations are consistent with an inhibitory role of leptin on food intake and fat mass development (rev. in 8).
Serum leptin levels are strongly correlated with BMI or fat mass, as evidenced by a number of studies. That led to the concept of an apparent resistance to leptin in common obesity, since high leptin levels appear unable to reduce fat storage, most likely through a defect in leptin transport to the brain (9).
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