Summary
The blood- brain barrier (BBB) has emerged as a regulatory interface that controls the exchange of informational molecules between the blood and the central nervous system (CNS) fluids (the brain interstitial and the cerebrospinal fluid). As such, it is a pivotal point in a humoral-based, endocrine-like communication between the CNS and peripheral tissues. For example, the BBB controls the entry of major feeding hormones into the CNS from the blood, including leptin. Impaired transport of leptin across the BBB is an early cause of leptin resistance. Leptin transport is regulated by alpha1-adrenergics, which simulate transport, and triglycerides, which inhibit it. The ability of triglycerides to inhibit leptin transport may have evolved as a response to the hypertriglyceridemia of starvation. If so, their ability to inhibit leptin transport in obesity may be a metabolic case of mistaken identity.
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References
Banks WA (1999) Physiology and pathophysiology of the blood-brain barrier: Implications for microbial pathogenesis, drug delivery and neurodegenerative disorders. J. Neurovirology 5:538–555
Banks WA (2001) Enhanced leptin transport across the blood-brain barrier by α1-adrenergic agents. Brain Res. 899:209–217
Banks WA, Clever CM, and Farrell CL (2000) Partial saturation and regional variation in the blood to brain transport of leptin in normal weight mice. Am. J. Physiol. 278:E1158–E1165
Banks WA, Coon AB, Robinson SM, Moinuddin A, Shultz JM, Nakaoke R, and Morley JE (2004) Triglycerides induce leptin resistance at the blood-brain barrier. Diabetes 53:1253–1260
Banks WA, DiPalma CR, and Farrell CL (1999) Impaired transport of leptin across the blood-brain barrier in obesity. Peptides 20:1341–1345
Banks WA and Farrell CL (2003) Impaired transport of leptin across the blood-brain barrier in obesity is acquired and reversible. Am J Physiology 285:E10–E15
Banks WA and Kastin AJ (1990) Editorial Review: Peptide transport systems for opiates across the blood-brain barrier. Am. J. Physiol. 259:E1–E10
Banks WA, Kastin AJ, Huang W, Jaspan JB, and Maness LM (1996) Leptin enters the brain by a saturable system independent of insulin. Peptides 17:305–311
Bottner A, Eisenhofer G, Torpy DJ, Ehrhart-Bornstein M, Keiser HR, Chrousos GP, and Bornstein SR (1999) Preliminary report: Lack of leptin suppression in response to hypersecretion of catecholamines in pheochromocytoma patients. Metab. Clin. Exp. 48:243–245
Brownlees J and Williams CH (1993) Peptidases, peptides, and the mammalian blood-brain barrier. J. Neurochem. 60:793–803
Brunetti L, Michelotto B, Orlando G, and Vacca M (1999) Leptin inhibits norepinephrine and dopamine release from rat hypothalamic neuronal ends. Eur. J. Pharmacol. 372:237–240
Cao GY, Considine RV, and Lynn RB (1997) Leptin receptors in the adrenal medulla of the rat. Am. J. Physiol. 273:E448–E452
Davson H (1967) The blood-brain barrier, in physiology of the Cerebrospinal Fluid pp 82–103, J. and A. Churchill, LTD., London
Davson H and Segal MB (1996) Physiology of the CSF and Blood-Brain Barriers. CRC Press, Boca Raton
Friedman JM and Halaas JL (1998) Leptin and the regulation of body weight in mammals. Nature 395:763–770
Fritsche A, Wahl HG, Metzinger E, Reen W, Kellerer M, Haring H, and Stumvoll M (1998) Evidence for inhibition of leptin secretion by catecholamines in man. Experimental and Clinical Endocrinology and Diabetes 106:415–418
Guerre-Millo M (1997) Regulation of ob gene and overexpression in obesity. Biomedicine and Pharmacotherapy 51:318–323
Hansen, B. C, Saye, J., and Wennogle, L. P. The metabolic Syndrome X: Convergence of insulin resistance, glucose intolerance, hypertension, obesity, and dyslipidemia — Searching for the underlying defects. Hansen, B. C, Saye, J., and Wennogle, L. P. (892), 1–336. 1999. New York, NY, The New York Academy of Sciences. Annals of the New York Academy of Sciences
Haynes WG, Morgan DA, Walsh SA, Mark AL, and Sivitz WI (1997) Receptor-mediated regional sympathetic nerve activation by leptin. J. Clin. Invest. 100:270–278
Kastin AJ and Akerstrom V (2000) Fasting, but not adrenalectomy, reduces transport of leptin into the brain. Peptides 21:679–682
Levin BE, Dunn-Meynell AA, and Banks WA (2004) Obesity-prone rats have normal blood-brain barrier transport but defective central leptin signaling before obesity onset. Am. J. Physiol. 286:R143–R150
Mantyh PW, Ghilardi JR, Rogers S, DeMaster E, Allen CJ, Stimson ER, and Maggio JE (1993) Aluminum, iron, and zinc ions promote aggregation of physiological concentration of β-amyloid peptide. J. Neurochem. 61:1171–1174
Mills PJ, Ziegler MG, and Morrison TA (1998) Leptin is related to epinephrine levels but not reproductive hormone levels in cycling African-American and Caucasian women. Life Sci. 63:617–623
Pelleymounter MA, Cullen MJ, Healy D, Hecht R, Winters D, and McCaleb M (1998) Efficacy of exogenous recombinant murine leptin in lean and obese 10-to 12-mo-old female CD-1 mice. Am. J. Physiol. 275:R950–R959
Reidy SP and Weber JM (2002) Accelerated substrate cycling: a new energy-wasting role for leptin in vivo. Am. J. Physiology 282:E312–E317
Steinberg GR, Bonen A, and Dyck DJ (2002) Fatty acid oxidation and triacylglycerol hydrolysis are enhanced after chronic leptin treatment in rats. Am. J. Physiol. 282:E593–E600
Takekoshi K, Motooka M, Isobe K, Nomura F, Manmoku T, Ishii K, and Nakai T (1999) Leptin directly stimulates catecholamine secretion and synthesis in cultured porcine adrenal medullary chromaffin cells. Biochem. Biophys. Res. Commun. 261:426–431
Zhang Y, Proenca R, Maffel M, Barone M, Leopold L, and Friedman JM (1994) Positional cloning of the mouse obese gene and its human homologue. Nature 372:425–432
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© 2006 Springer-Verlag Tokyo
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Banks, W.A., Farr, S.A., Morley, J.E. (2006). The Role of the Blood-Brain Barrier in Feeding: Leptin. In: Homma, I., Shioda, S. (eds) Breathing, Feeding, and Neuroprotection. Springer, Tokyo. https://doi.org/10.1007/4-431-28775-2_4
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DOI: https://doi.org/10.1007/4-431-28775-2_4
Publisher Name: Springer, Tokyo
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