Is brain uptake of leptin in vivo saturable and reduced by fasting?

Karonen, Sirkka-Liisa; Koistinen, Hannu; Nikkinen, Päivi; Koivisto, Veikko A.

doi:10.1007/s002590050262

Cited by 29 publications

(16 citation statements)

References 33 publications

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“…Leptin does not leave the bloodstream until reaching the particular target areas by this mechanism (29). In agreement with these studies, Karonen et al (36) showed that the in vivo uptake of 123 I-leptin occurred in the choroid plexus, lung, and kidney of rabbits. In support of this concept, the expression of the OB-Ra and OB-Rb mRNA in rat brain microvessels was recently described by Bjorbaek et al (27) using in situ hybridization and reverse transcriptase-polymerase chain reaction analysis (27).…”

Section: Discussionmentioning

confidence: 68%

“…The lack of leptin access into the brain could then be responsible for obesity (32)(33)(34)(35). Several authors have suggested that leptin crosses the BBB by a saturable transport mechanism (33,36). The presence of saturable transport mechanisms between the blood and the CSF could explain why a significant increase in the levels of plasma leptin, as occurs in obesity, corresponds with smaller changes of leptin levels in the CSF.…”

Section: Discussionmentioning

confidence: 99%

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Obesity is associated with a decreased leptin transport across the blood-brain barrier in rats.

et al. 2000

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Leptin exerts important effects on the regulation of food intake and energy expenditure by acting in the brain. Leptin is secreted by adipocytes into the bloodstream and must gain access to specific regions in the brain involved in regulating energy balance. Its action is mediated by interaction with a receptor that is mainly expressed in the hypothalamus but is also present in other cerebral areas. To reach these target areas, leptin most likely needs to cross the blood-brain barrier (BBB). In this study, we compared the permeability of leptin at the BBB in homozygous lean (FA/FA), high-fat diet-induced (HFD) obese rats (FA/FA rats on a highfat diet), and genetically obese fa/fa Zucker rats by quantifying the permeability coefficient surface area (PS) product after correction for the residual plasma volume (V p ) occupied by leptin in the vessel bed of different brain regions. The intravenous bolus injection technique was used in the cannulated brachial vein and artery using leptin radioiodinated with 2 isotopes of iodine ( 125 I and 131 I) to separately determine the PS and V p values. The PS for leptin at the BBB in lean FA/FA rats ranged from 11.0 ± 1.6 at the cortex to 14.8 ± 1.4 ؋ 10 -6 ml · g -1 · ml -1 at the posterior hypothalamus. The PS for leptin in HFD obese FA/FA and obese fa/fa rats ranged from 3.0-to 4.0-fold lower than in lean FA/FA rats. The V p values were not significantly different among the 3 groups studied. SDS-PAGE analysis of the radioiodinated leptin after 60 min of uptake revealed intact protein in the 8 different brain regions. Plasma leptin levels were significantly higher in both obese rat groups compared with those in lean FA/FA rats. Leptin levels in cerebrospinal fluid were not significantly different among the 3 groups of rats. These findings strongly suggest that the leptin receptor (OB-R) in the BBB can be easily saturated. Saturation of the BBB OB-R in obese individuals would explain the defect in leptin transport into the brain described in this study.

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Section: Discussionmentioning

confidence: 68%

Section: Discussionmentioning

confidence: 99%

Obesity is associated with a decreased leptin transport across the blood-brain barrier in rats.

et al. 2000

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“…Leptin was iodinated by the solid lactoperoxidase method 37. The coefficient of variation of the assay was 12%.…”

Section: Methodsmentioning

confidence: 99%

Postnatal changes in concentrations of free and bound leptin

Juntunen²,

Ha³

et al. 2001

Archives of Disease in Childhood - Fetal and Neonatal Edition

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Aim-To evaluate the eVect of maternal diabetes on the concentrations of free and bound leptin at birth and during postnatal adaptation. Methods-Total, bound, and free leptin concentrations and the percentage of free leptin were measured in cord plasma and plasma at 3 days of age of 13 term infants of mothers with gestational diabetes mellitus (GDM) and 13 term infants of healthy mothers. Gestational age was 40.2 (1.4) weeks, and birth weight was 3693 (549) g (means (SD)). Results-At birth, infants of mothers with GDM had significantly higher concentrations of total, bound, and free leptin and a higher percentage of free leptin (all p < 0.05). In all infants, these concentrations were significantly lower at 3 days of age than at birth (all p < 0.003), and the diVerences in concentrations of total, bound, and free leptin between the two groups were no longer significant. In infants of mothers with GDM, the percentage of free leptin remained unchanged, and was higher (p<0.05) than in infants of healthy mothers; in the latter group the percentage of free leptin significantly declined (p = 0.02).Conclusions-GDM appears to influence fetoplacental leptin metabolism. This effect may be mediated through altered maternal glucose metabolism, or insulinaemia, or both. (Arch Dis Child Fetal Neonatal Ed 2001;85:F123-F126)

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“…Furthermore, in accordance with the view that the target for the action of peripheral leptin is within the hypothalamus, peripheral leptin administration has been shown to increase the expression of immediate-early gene c- fos , a putative marker for neuronal activation in the hypothalamus [15]. Similarly, leptin uptake has been demonstrated in the brain after peripheral administration of radioiodinated leptin ( 123 I-leptin) [16]. …”

Section: Discussionmentioning

confidence: 78%

Serum Leptin and Regional Cerebral Blood Flow during Exposure to Food in Obese and Normal-Weight Women

Karhunen

Lappalainen²,

Vanninen³

et al. 1999

Neuroendocrinology

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Leptin is an adipocyte-derived product of the ob gene thought to be involved in the regulation of eating. Receptors for leptin have been found in multiple regions in the brain. In particular, hypothalamic receptors seem to be of fundamental importance for the biological effects of leptin. However, the association of leptin with cerebral function in humans has not been studied. Therefore, in order to assess the possible functional relationships between leptin and cerebral activity in humans, simultaneous serum leptin and regional cerebral blood flow (rCBF) measurements were made in 10 obese [BMI 33.5 (29.3–39.1) kg/m²] and 12 normal-weight [BMI 22.2 (20.3–24.6) kg/m²] women during exposure to food. The rCBF measurements were performed by ^99mTc-ethyl-cysteine-dimer single photon emission computed tomography. A strong inverse association was observed between the leptin and rCBF of hypothalamus during the exposure to food in the obese (r = –0.73, p = 0.02, n = 10), but not in the normal-weight subjects (r = 0.22, p = 0.48, n = 12). This suggests that the association of leptin with cerebral activity could be different in obese and normal-weight women; depressed activity of hypothalamic neurones in response to the high peripheral leptin concentration could be postulated to occur in obese women during exposure to food.

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Is brain uptake of leptin in vivo saturable and reduced by fasting?

Cited by 29 publications

References 33 publications

Obesity is associated with a decreased leptin transport across the blood-brain barrier in rats.

Obesity is associated with a decreased leptin transport across the blood-brain barrier in rats.

Postnatal changes in concentrations of free and bound leptin

Serum Leptin and Regional Cerebral Blood Flow during Exposure to Food in Obese and Normal-Weight Women

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