Decreased transport of leptin across the blood–brain barrier in rats lacking the short form of the leptin receptor☆

Kastin, Abba J.; Pan, Weihong; Maness, Lawrence M.; Koletsky, Richard J.; Ernsberger, Paul

doi:10.1016/s0196-9781(99)00156-4

Cited by 177 publications

(113 citation statements)

References 19 publications

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“…In rats (18), leptin transfer from serum to CSF is dependent on ObR receptors located in the blood-brain barrier. Obesity is associated with decreased leptin transport, suggesting that the leptin receptor in the blood-brain barrier can be easily FIG.…”

Section: Discussionmentioning

confidence: 99%

Mutations in the Human Leptin and Leptin Receptor Genes as Models of Serum Leptin Receptor Regulation

Lahlou

Issad²,

Lebouc³

et al. 2002

Diabetes

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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.

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Section: Discussionmentioning

confidence: 99%

Mutations in the Human Leptin and Leptin Receptor Genes as Models of Serum Leptin Receptor Regulation

Lahlou

Issad²,

Lebouc³

et al. 2002

Diabetes

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“…The major peripheral sources of leptin, adipocytes and stomach, secrete leptin in a pulsatile fashion [6,109,110]. The short isoform of the leptin receptor located in the endothelium of the vasculature and epithelium of the choroid plexus of the circumventricular organs most likely transports leptin across the BBB [19,52,63,85,87,112]. A variety of endogenous factors that modify the dynamics of leptin entry across BBB are the following:…”

Section: Leptin Availability In the Brainmentioning

confidence: 99%

Central leptin insufficiency syndrome: An interactive etiology for obesity, metabolic and neural diseases and for designing new therapeutic interventions

Kalra

2008

Peptides

117

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This review critically reappraises recent scientific evidence concerning central leptin insufficiency versus leptin resistance formulations to explain metabolic and neural disorders resulting from subnormal or defective leptin signaling in various sites in the brain. Research at various fronts to unravel the complexities of the neurobiology of leptin is surveyed to provide a comprehensive account of the neural and metabolic effects of environmentally-imposed fluctuations in leptin availability at brain sites and the outcome of newer technology to restore leptin signaling in a sitespecific manner. The cumulative new knowledge favors a unified central leptin insufficiency syndrome over the, in vogue, central resistance hypothesis to explain the global adverse impact of deficient leptin signaling in the brain. Furthermore, the leptin insufficiency syndrome delineates a novel role of leptin in the hypothalamus in restraining rhythmic pancreatic insulin secretion while concomitantly enhancing glucose metabolism and non-shivering thermogenic energy expenditure, sequalae that would otherwise promote fat accrual to store excess energy resulting from consumption of energy-enriched diets. A concerted effort should now focus on development of newer technologies for delivery of leptin or leptin mimetics to specifically target neural pathways for remediation of diverse ailments encompassing the central leptin insufficiency syndrome.

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“…The MAPK (mitogen activated protein kinase) patway can also be stimulated by Ob-Rb and ObRa, although to lesser extent by the latter (Fruhbeck, 2006). In addition, Ob-Ra is thought to mediate leptin transport across anatomical barriers, such as the bloodbrain barrier (Kastin et al, 1999) and the placenta (Smith and Waddell, 2002). Both Ob-Rb and Ob-Ra mediate also leptin internalization and its lysosomal degradation (Uotani et al, 1999) Ob-Re, which lacks the transmembrane and intracellular domain, serves as soluble receptor and represents the leptin bioavailability, being the hormone binding protein in plasma (Zastrow et al, 2003).…”

mentioning

confidence: 99%

Leptin and Its Receptor Are Expressed in the Testis and in the Epididymis of Young and Adult Pigs

Rago

Aquila

Guido

et al. 2009

The Anatomical Record

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Recent studies indicated that leptin, a 16 kDa hormone, is a regulatory signal in human and rodent male reproduction. This work was designed to investigate the expression of leptin and its receptor in testes and epididymides from immature and mature pigs. Immunolocalization revealed that leptin and its receptor were confined only in the interstitial compartment of immature testes, whereas both proteins were detected in Leydig cells and within seminiferous tubules of mature gonads. The immunostaining of epididymal tissues showed that leptin was absent in the epithelial cells of immature pigs but it was present in all the three regions of mature epididymides, although with a minor signal in the cauda. Conversely, leptin receptor was observed in all the epithelial cells of both immature and mature epididymides. Western blot analysis of tissue extracts detected a 16 kDa band for leptin and five/six isoforms, ranging from 120 to 40 kDa, for leptin receptor. In conclusion, this work has identified, for the first time, leptin and leptin receptor in the testis and in the epididymis of the pig showing a differential cell-type expression pattern of the two proteins in young and adult animals. Therefore, our findings suggest a possible involvement of leptin in endocrine or autocrine/ paracrine control of porcine male reproductive structures. Anat Rec, 292:736-745, 2009. V V C 2009 Wiley-Liss, Inc.

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Decreased transport of leptin across the blood–brain barrier in rats lacking the short form of the leptin receptor☆

Cited by 177 publications

References 19 publications

Mutations in the Human Leptin and Leptin Receptor Genes as Models of Serum Leptin Receptor Regulation

Mutations in the Human Leptin and Leptin Receptor Genes as Models of Serum Leptin Receptor Regulation

Central leptin insufficiency syndrome: An interactive etiology for obesity, metabolic and neural diseases and for designing new therapeutic interventions

Leptin and Its Receptor Are Expressed in the Testis and in the Epididymis of Young and Adult Pigs

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