title: Estrogen and insulin transport through the blood-brain barrier.
abstract: Obesity is associated with insulin resistance and reduced transport of insulin through the blood-brain barrier (BBB). Reversal of high-fat diet-induced obesity (HFD-DIO) by dietary intervention improves the transport of insulin through the BBB and the sensitivity of insulin in the brain. Although both insulin and estrogen (E2), when given alone, reduce food intake and body weight via the brain, E2 actually renders the brain relatively insensitive to insulin's catabolic action. The objective of these studies was to determine if E2 influences the ability of insulin to be transported into the brain, since the receptors for both E2 and insulin are found in BBB endothelial cells. E2 (acute or chronic) was systemically administered to ovariectomized (OVX) female rats and male rats fed a chow or a high-fat diet. Food intake, body weight and other metabolic parameters were assessed along with insulin entry into the cerebrospinal fluid (CSF). Acute E2 treatment in OVX female and male rats reduced body weight and food intake, and chronic E2 treatment prevented or partially reversed high-fat diet-induced obesity. However, none of these conditions increased insulin transport into the CNS; rather, chronic E2 treatment was associated less-effective insulin transport into the CNS relative to weight-matched controls. Thus, the reduction of brain insulin sensitivity by E2 is unlikely to be mediated by increasing the amount of insulin entering the CNS.
authors.affiliation: Department of Pathology and Molecular Medicine, Metabolic Diseases Institute, University of Cincinnati College of Medicine, OH, USA.
authors.forename: Aaron A
authors.initials: AA
authors.lastname: May
authors.affiliation: Department of Pathology and Molecular Medicine, Metabolic Diseases Institute, University of Cincinnati College of Medicine, OH, USA.
authors.forename: Nicholas D
authors.initials: ND
authors.lastname: Bedel
authors.affiliation: Department of Pathology and Molecular Medicine, Metabolic Diseases Institute, University of Cincinnati College of Medicine, OH, USA.
authors.forename: Ling
authors.initials: L
authors.lastname: Shen
authors.affiliation: Department of Psychiatry and Behavioral Neuroscience, Metabolic Diseases Institute, University of Cincinnati College of Medicine, OH, USA.
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Woods
authors.affiliation: Department of Pathology and Molecular Medicine, Metabolic Diseases Institute, University of Cincinnati College of Medicine, OH, USA. Electronic address: min.liu@uc.edu.
authors.forename: Min
authors.initials: M
authors.lastname: Liu
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000818:Animals; D001808:Blood Vessels / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000378:metabolism*; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000473:pathology; D004041:Dietary Fats; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D008297:Male; D009765:Obesity / Q000378:metabolism; D010052:Ovariectomy; D051381:Rats; D020318:Rats, Long-Evans; D016708:Synaptophysin / Q000378:metabolism
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D004041:Dietary Fats; D004967:Estrogens; D051272:Glucose Transporter Type 1; D007328:Insulin; D016708:Synaptophysin
keywords: 17β-Estradiol; Blood-brain barrier; CNS insulin transport; Diet-induced obesity; Insulin resistance; Metabolic syndrome