title: Central transthyretin acts to decrease food intake and body weight.
abstract: Transthyretin (TTR) is a blood and cerebrospinal fluid transporter of thyroxine and retinol. Gene expression profiling revealed an elevation of Ttr expression in the dorsomedial hypothalamus (DMH) of rats with exercise-induced anorexia, implying that central TTR may also play a functional role in modulating food intake and energy balance. To test this hypothesis, we have examined the effects of brain TTR on food intake and body weight and have further determined hypothalamic signaling that may underlie its feeding effect in rats. We found that intracerebroventricular (icv) administration of TTR in normal growing rats decreased food intake and body weight. This effect was not due to sickness as icv TTR did not cause a conditioned taste aversion. ICV TTR decreased neuropeptide Y (NPY) levels in the DMH and the paraventricular nucleus (P < 0.05). Chronic icv infusion of TTR in Otsuka Long-Evans Tokushima Fatty rats reversed hyperphagia and obesity and reduced DMH NPY levels. Overall, these results demonstrate a previously unknown anorectic action of central TTR in the control of energy balance, providing a potential novel target for treating obesity and its comorbidities.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.|Department of Endocrinology, The Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, China.
authors.forename: Fenping
authors.initials: F
authors.lastname: Zheng
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: Yonwook J
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: Timothy H
authors.initials: TH
authors.lastname: Moran
authors.affiliation: Department of Endocrinology, The Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: Sheng
authors.initials: S
authors.lastname: Bi
mesh_terms: D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects / Q000378:metabolism; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects*; D002478:Cells, Cultured; D004435:Eating / Q000187:drug effects*; D020869:Gene Expression Profiling / Q000379:methods; D006963:Hyperphagia / Q000378:metabolism / Q000517:prevention & control*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D057967:Infusions, Intraventricular; D008297:Male; D009478:Neuropeptide Y / Q000378:metabolism; D009765:Obesity / Q000378:metabolism / Q000517:prevention & control*; D020411:Oligonucleotide Array Sequence Analysis; D011228:Prealbumin / Q000008:administration & dosage / Q000494:pharmacology* / Q000502:physiology; D020334:Rats, Inbred OLETF; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D009478:Neuropeptide Y; D011228:Prealbumin