Expression of the long and short leptin receptor isoforms in peripheral blood mononuclear cells: Implications for leptin's actions

Tsiotra, Panayoula C.; Pappa, Vassiliki; Raptis, Sotirios A.; Tsigos, Constantine

doi:10.1053/meta.2000.18519

Cited by 63 publications

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“…[18][19][20] We observed that Lep-R(S) mRNA levels in tumor tissue are much higher (14 times) than Lep-R(L) mRNA levels in breast tumor tissue. This is consistent with the previously reported finding that Lep-R(S) levels were 8 times higher than Lep-R(L) levels in peripheral blood mononuclear cells, 21 and suggests that Lep-R(S) may play a more important role than Lep-R(L) in the signal transduction of leptin. However, since it has been demonstrated that the growth stimulation of leptin in T-47D breast cancer cells is blocked not only by a MAPK inhibitor 13 but also by a STAT3 inhibitor, 8 it can be hypothesized that not only the Lep-R(S) pathway (mainly the MAPK pathway) but also the Lep-R(L) pathway (both the MAPK and STAT3 pathway) plays an important role in the growth-signal transduction of leptin in breast cancer cells.…”

Section: Discussionsupporting

confidence: 93%

High expression of leptin receptor mRNA in breast cancer tissue predicts poor prognosis for patients with high, but not low, serum leptin levels

et al. 2005

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Section: Discussionsupporting

confidence: 93%

High expression of leptin receptor mRNA in breast cancer tissue predicts poor prognosis for patients with high, but not low, serum leptin levels

et al. 2005

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“…There is evidence suggesting that the expression of leptin receptors is sensitive to experimentally induced changes in circulating leptin, 25,26 and, consistent with our findings, it has been recently shown that, in healthy humans, an inverse correlation exists between the two major leptin receptor splice variants, expressed on mononuclear cells, and both the degree of adiposity and the circulating leptin concentrations. 27 This may have important therapeutic implications in AN. Indeed, it is known that during the therapeutically induced regaining in BW, leptin secretion increases; 6 hence, the presence of an upregulated leptin receptor might theoretically result in a potentiation of leptin actions leading to excessive appetite suppression and energy expenditure, that contrast with the therapeutic process.…”

Section: Discussionmentioning

confidence: 99%

Opposite modifications in circulating leptin and soluble leptin receptor across the eating disorder spectrum

et al. 2002

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Leptin is thought to modulate feeding behaviour, body weight and energy metabolism by acting through specific cellular receptors. Derangements of leptin production have been repeatedly reported in patients with anorexia nervosa (AN) or bulimia nervosa (BN), but no information has been provided on the functional status of leptin receptors in these disorders. Therefore, we measured plasma levels of leptin and its soluble receptor (Ob-Re) in a total of 130 women, including 22 patients with AN, 45 patients with BN, 18 patients with the bingeeating disorder (BED), 12 non-binge eating obese women and 33 healthy women. Circulating leptin was drastically reduced in underweight anorexics and normal-weight bulimics, but increased in overweight BED patients and non-binge-eating obese women. Conversely, plasma levels of Ob-Re were significantly increased in patients with AN or BN, but decreased in BED and non-binge-eating obese women. Significant inverse correlations were detected between plasma levels of leptin and those of Ob-Re in all the subject groups, except in nonbinge-eating obese subjects. These results show, for the first time, that opposite modifications occur in circulating levels of leptin and Ob-Re across the eating-disorder spectrum. The relevance of these findings to the pathophysiology and treatment of eating disorders remains to be elucidated.

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“…U66495) was quantified in circulating human mononuclear cells by RT-PCR as previously described (15). Blood samples (10 ml) were collected from five healthy men (mean BMI 22.2 Ϯ 0.4 kg/m 2 ) at 8:00 A.M. on 3 consecutive days of fasting.…”

Section: Study Designsmentioning

confidence: 99%

“…Blood samples (10 ml) were collected from five healthy men (mean BMI 22.2 Ϯ 0.4 kg/m 2 ) at 8:00 A.M. on 3 consecutive days of fasting. Isolation of total RNA and the RT-PCR reaction (using 1 g total RNA) were performed as previously described (15). Statistical analysis.…”

Section: Study Designsmentioning

confidence: 99%

Regulation of Circulating Soluble Leptin Receptor Levels By Gender, Adiposity, Sex Steroids, and Leptin

Blüher²,

et al. 2002

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Leptin is an adipocyte-secreted hormone important in energy homeostasis and diverse physiological processes. A circulating soluble form of the leptin receptor [soluble leptin receptor (sOB-R)] is the main leptinbinding protein and determinant of free leptin index (FLI), the presumed biologically active form of leptin. We performed observational and interventional studies to elucidate the regulation of sOB-R and FLI in humans. In a cross-sectional study (n ‫؍‬ 118), leptin, gender, and adiposity were significant determinants of sOB-R. By multivariate analysis, estradiol (E2) and testosterone predict sOB-R, whereas insulin predicts leptin and FLI. In a frequent-sampling study (n ‫؍‬ 6), sOB-R followed a significant circadian rhythm inverse to that of leptin, suggesting that leptin's biological activity may have an even more pronounced diurnal variation than originally thought. A 72-h fast in eight men decreased leptin levels by 80% and increased lymphocyte expression of leptin receptor mRNA and serum sOB-R levels by 100%. Physiological and pharmacological doses of recombinantmethionyl human leptin (rhLeptin) administered to fasted men prevented the fasting-induced increase of sOB-R levels, and pharmacological doses resulted in a decrease in sOB-R levels. These studies provide evidence that sOB-R is regulated by gender, adiposity, hormones, and rhLeptin administration. This may have important implications for the biological activity of leptin in disease states associated with abnormal leptin levels (e.g., obesity and anorexia nervosa). Diabetes 51: 2105-2112, 2002 L eptin, the protein product of the ob gene, is produced by adipose tissue and is secreted into circulation. It acts mainly in the hypothalamus but also in other tissues by binding to specific leptin receptors, which belong to the cytokine receptor family (1,2). Multiple isoforms of the leptin receptor are generated through alternative splicing of the leptin receptor gene, including a long isoform expressed primarily in the hypothalamus and several short isoforms with a much wider tissue distribution (3). A soluble form of the leptin receptor [soluble leptin receptor (sOB-R)], consisting of only the extracellular region (4), binds leptin with an affinity similar to that of membrane-bound receptors (5) and represents the main leptin binding activity in serum (6).Recent work in rodent models has demonstrated that the sOB-R modulates serum leptin levels by delaying its clearance and determines the amount of free versus bound leptin in serum (7). It has also been proposed that free leptin, the form present in cerebrospinal fluid (CSF), is the biologically active form of leptin (8). These data suggest that sOB-R plays an important role in the pathophysiology of energy homeostasis in rodents (7) and humans (9). Thus, understanding the regulation of circulating sOB-R and free leptin in humans may have important physiological and therapeutic implications for human obesity and eating disorders.In obese subjects, a significantly higher percentage of leptin circulat...

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Expression of the long and short leptin receptor isoforms in peripheral blood mononuclear cells: Implications for leptin's actions

Cited by 63 publications

References 0 publications

High expression of leptin receptor mRNA in breast cancer tissue predicts poor prognosis for patients with high, but not low, serum leptin levels

High expression of leptin receptor mRNA in breast cancer tissue predicts poor prognosis for patients with high, but not low, serum leptin levels

Opposite modifications in circulating leptin and soluble leptin receptor across the eating disorder spectrum

Regulation of Circulating Soluble Leptin Receptor Levels By Gender, Adiposity, Sex Steroids, and Leptin

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