Brain‐derived neurotrophic factor, corticotropin‐releasing factor, and hypothalamic neuronal histamine interact to regulate feeding behavior

Gotoh, Koro; Masaki, Takayuki; Chiba, Seiichi; Ando, Hisae; Fujiwara, Kansuke; Shimasaki, Takanobu; Mitsutomi, Kimihiko; Katsuragi, Isao; Kakuma, Tatsuyuki; Sakata, Toshiie; Yoshimatsu, Hironobu

doi:10.1111/jnc.12213

Cited by 17 publications

(12 citation statements)

References 34 publications

(36 reference statements)

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“…In more detail: (a) in animal models the central infusion of BDNF induces weight loss 66,67 . The suppressive effects of BDNF on feeding behavior and body weight are mediated by corticotropin-releasing factor (CRF) and hypothalamic neuronal histamine in mice 68 . BDNF signaling is altered by reduced BDNF expression in the hippocampus, in activity-based anorexia in mice 69 and in immobilization stress induced anorexia in rats 70 .…”

Section: Discussionmentioning

confidence: 99%

Evidence for three genetic loci involved in both anorexia nervosa risk and variation of body mass index

et al. 2016

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The maintenance of normal body weight is disrupted in patients with anorexia nervosa (AN) for prolonged periods of time. Prior to the onset of AN, premorbid body mass index (BMI) spans the entire range from underweight to obese. After recovery, patients have reduced rates of overweight and obesity. As such, loci involved in body weight regulation may also be relevant for AN and vice versa. Our primary analysis comprised a cross-trait analysis of the 1000 single nucleotide polymorphisms (SNPs) with the lowest p-values in a genome-wide association meta-analysis (GWAMA) of AN (GCAN) for evidence of association in the largest published GWAMA for BMI (GIANT). Subsequently we performed sex-stratified analyses for these 1000 SNPs. Functional ex vivo studies on four genes ensued. Lastly, a look-up of GWAMA-derived BMI related loci was performed in the AN GWAMA. We detected significant associations (p-values < 5×10−5, Bonferroni corrected p < 0.05) for 9 SNP alleles at 3 independent loci. Interestingly, all AN susceptibility alleles were consistently associated with increased BMI. None of the genes (chr. 10: CTBP2, chr. 19: CCNE1, chr. 2: CARF and NBEAL1; the latter is a region with high linkage disequilibrium) nearest to these SNPs has previously been associated with AN or obesity. Sex-stratified analyses revealed that the strongest BMI signal originated predominantly from females (chr. 10 rs1561589; poverall: 2.47 × 10−06/pfemales: 3.45 × 10−07/pmales: 0.043). Functional ex vivo studies in mice revealed reduced hypothalamic expression of Ctbp2 and Nbeal1 after fasting. Hypothalamic expression of Ctbp2 was increased in diet induced obese (DIO) mice as compared to age-matched lean controls. We observed no evidence for associations for the look-up of BMI related loci in the AN GWAMA. A cross-trait analysis of AN and BMI loci revealed variants at three chromosomal loci with potential joint impact. The chromosome 10 locus is particularly promising given that the association with obesity was primarily driven by females. In addition, the detected altered hypothalamic expression patterns of Ctbp2 and Nbeal1 as a result of fasting and DIO implicate these genes in weight regulation.

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Section: Discussionmentioning

confidence: 99%

Evidence for three genetic loci involved in both anorexia nervosa risk and variation of body mass index

et al. 2016

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“…Inhibition of ERa signaling in this nucleus is associated with hyperphagia, obesity, decreased glucose tolerance, and reduced energy expenditure (Musatov et al 2007). Brain-derived neurotrophic factor (Gotoh et al 2013) and urocortin (Chen et al 2012) are the anorexigenic peptides secreted by neurons of the ventromedial hypothalamus.…”

Section: Cnsmentioning

confidence: 99%

Insight into the mechanisms of action of estrogen receptor β in the breast, prostate, colon, and CNS

Dey¹,

Barros

Warner

et al. 2013

Journal of Molecular Endocrinology

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Estrogen and its receptors (ERs) influence many biological processes in physiology and pathology in men and women. ERs are involved in the etiology and/or progression of cancers of the prostate, breast, uterus, ovary, colon, lung, stomach, and malignancies of the immune system. In estrogen-sensitive malignancies, ERb usually is a tumor suppressor and ERa is an oncogene. ERb regulates genes in several key pathways including tumor suppression (p53, PTEN); metabolism (PI3K); survival (Akt); proliferation pathways (p45 Skp2 , cMyc, and cyclin E);cell-cycle arresting factors (p21 WAF1

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“…This introduces a remarkable but challenging yin-yang dichotomy because evidence points to histamine being an anorexigenic signaling neurotransmitter [74]. Histaminergic control is complex and includes leptin [75], CRH [76], nesfatin-1 [77], and thyrotropin releasing hormone (TRH) [78], all of which are peripheral or central satiety signals. The blunting of appetite via histamine appears to be initiated by leptin [79]; however, since circulating levels of leptin decrease significantly in sleep-deprived or restricted rats [14, 17, 19, 80], the hyperphagic response is not surprising.…”

Section: Discussionmentioning

confidence: 99%

Hypothalamic L-Histidine Decarboxylase Is Up-Regulated During Chronic REM Sleep Deprivation of Rats

Hoffman

Koban

2016

PLoS ONE

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A competition of neurobehavioral drives of sleep and wakefulness occurs during sleep deprivation. When enforced chronically, subjects must remain awake. This study examines histaminergic neurons of the tuberomammillary nucleus of the posterior hypothalamus in response to enforced wakefulness in rats. We tested the hypothesis that the rate-limiting enzyme for histamine biosynthesis, L-histidine decarboxylase (HDC), would be up-regulated during chronic rapid eye movement sleep deprivation (REM-SD) because histamine plays a major role in maintaining wakefulness. Archived brain tissues of male Sprague Dawley rats from a previous study were used. Rats had been subjected to REM-SD by the flowerpot paradigm for 5, 10, or 15 days. For immunocytochemistry, rats were transcardially perfused with acrolein-paraformaldehyde for immunodetection of L-HDC; separate controls used carbodiimide-paraformaldehyde for immunodetection of histamine. Immunolocalization of histamine within the tuberomammillary nucleus was validated using carbodiimide. Because HDC antiserum has cross-reactivity with other decarboxylases at high antibody concentrations, titrations localized L-HDC to only tuberomammillary nucleus at a dilution of ≥ 1:300,000. REM-SD increased immunoreactive HDC by day 5 and it remained elevated in both dorsal and ventral aspects of the tuberomammillary complex. Our results suggest that up-regulation of L-HDC within the tuberomammillary complex during chronic REM-SD may be responsible for maintaining wakefulness.

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Brain‐derived neurotrophic factor, corticotropin‐releasing factor, and hypothalamic neuronal histamine interact to regulate feeding behavior

Cited by 17 publications

References 34 publications

Evidence for three genetic loci involved in both anorexia nervosa risk and variation of body mass index

Evidence for three genetic loci involved in both anorexia nervosa risk and variation of body mass index

Insight into the mechanisms of action of estrogen receptor β in the breast, prostate, colon, and CNS

Hypothalamic L-Histidine Decarboxylase Is Up-Regulated During Chronic REM Sleep Deprivation of Rats

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