Obesity-inducing lesions of the central nervous system alter leptin uptake by the blood-brain barrier

被引:24
作者
Banks, WA
King, BM
Rossiter, KN
Olson, RD
Olson, GA
Kastin, AJ
机构
[1] St Louis Univ, Sch Med, Dept Internal Med, Div Geriatr, St Louis, MO USA
[2] Univ New Orleans, Dept Psychol, New Orleans, LA 70148 USA
[3] Vet Affairs Med Ctr, New Orleans, LA USA
[4] Tulane Univ, Sch Med, New Orleans, LA 70112 USA
[5] Vet Affairs Med Ctr, GRECC, St Louis, MO USA
关键词
leptin; blood-brain barrier; obesity; ventromedial hypothalamus (VMH); paraventricular nucleus (PVN); amygdala; posterior division of the amygdala (PDA); transport; resistance;
D O I
10.1016/S0024-3205(01)01346-7
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Leptin regulates body adiposity by decreasing feeding and increasing thermogenesis. Obese humans and some obese rodents are resistant to peripherally administered leptin, suggesting a defect in the transport of leptin across the blood-brain barrier (BBB). Defective transport of exogenous leptin occurs in some models of obesity, but in other models transport is normal. This shows that factors other than obesity are associated with impairment of leptin transport across the BBB. In order to further investigate these factors, we determined leptin transport in rats made obese by lesioning of the ventromedial hypothalamus (VMH), paraventricular nucleus (PVN), or posterodorsal amygdala (PDA). These regions all contain leptin receptors and lesions there induce obesity and hyperleptinemia and alter the levels of many feeding hormones which might participate in leptin transporter regulation. We measured the uptake of radioactively labeled leptin by the BBB by multiple-time regression analysis which divides uptake into a reversible phase (Vi, e.g., receptor/transporter binding to the brain endothelial cell) and an irreversible phase (Ki, complete transport across the BBB). Leptin uptake was not affected in rats with VMH lesions. No significant change occurred in the entry rate (Ki) for any group, although Ki declined by over 35% in rats with PVN lesions. Decreased uptake was observed in rats with PVN lesions and with PDA lesions. This was primarily due to a reduced Vi (about 21% for the PDA). This decreased uptake is most likely explained by decreased binding of leptin to the brain endothelial cell, which could be because of decreased binding by either receptors or transporters. This suggests that some of the feeding hormones controlled by the PVN and PDA may participate in regulating leptin uptake by the BBB. (C) 2001 Elsevier Science Inc. All rights reserved.
引用
收藏
页码:2765 / 2773
页数:9
相关论文
共 36 条
  • [1] Partial saturation and regional variation in the blood-to-brain transport of leptin in normal weight mice
    Banks, WA
    Clever, CM
    Farrell, CL
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, 2000, 278 (06): : E1158 - E1165
  • [2] Leptin enters the brain by a saturable system independent of insulin
    Banks, WA
    Kastin, AJ
    Huang, WT
    Jaspan, JB
    Maness, LM
    [J]. PEPTIDES, 1996, 17 (02) : 305 - 311
  • [3] Impaired transport of leptin across the blood-brain barrier in obesity
    Banks, WA
    DiPalma, CR
    Farrell, CL
    [J]. PEPTIDES, 1999, 20 (11) : 1341 - 1345
  • [4] Expression of leptin receptor isoforms in rat brain microvessels
    Bjorbæk, C
    Elmquist, JK
    Michl, P
    Ahima, RS
    van Bueren, A
    McCall, AL
    Flier, JS
    [J]. ENDOCRINOLOGY, 1998, 139 (08) : 3485 - 3491
  • [5] TRANSPORT OF ALPHA-AMINOISOBUTYRIC-ACID ACROSS BRAIN CAPILLARY AND CELLULAR MEMBRANES
    BLASBERG, RG
    FENSTERMACHER, JD
    PATLAK, CS
    [J]. JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 1983, 3 (01) : 8 - 32
  • [6] Obesity is associated with a decreased leptin transport across the blood-brain barrier in rats
    Burguera, B
    Couce, ME
    Curran, GL
    Jensen, MD
    Lloyd, RV
    Cleary, MP
    Poduslo, JF
    [J]. DIABETES, 2000, 49 (07) : 1219 - 1223
  • [7] RECOMBINANT MOUSE OB PROTEIN - EVIDENCE FOR A PERIPHERAL SIGNAL LINKING ADIPOSITY AND CENTRAL NEURAL NETWORKS
    CAMPFIELD, LA
    SMITH, FJ
    GUISEZ, Y
    DEVOS, R
    BURN, P
    [J]. SCIENCE, 1995, 269 (5223) : 546 - 549
  • [8] Decreased cerebrospinal-fluid/serum leptin ratio in obesity: A possible mechanism for leptin resistance
    Caro, JF
    Kolaczynski, JW
    Nyce, MR
    Ohannesian, JP
    Opentanova, I
    Goldman, WH
    Lynn, RB
    Zhang, PL
    Sinha, MK
    Considine, RV
    [J]. LANCET, 1996, 348 (9021) : 159 - 161
  • [9] Ultrastructural immunolocalization of leptin receptor in mouse brain
    De Matteis, R
    Cinti, S
    [J]. NEUROENDOCRINOLOGY, 1998, 68 (06) : 412 - 419
  • [10] Disruption in neuropeptide Y and leptin signaling in obese ventromedial hypothalamic-lesioned rats
    Dube, MG
    Xu, B
    Kalra, PS
    Sninsky, CA
    Kalra, SP
    [J]. BRAIN RESEARCH, 1999, 816 (01) : 38 - 46