Central action of acidic fibroblast growth factor in feeding regulation

Hanai, Kazuhiko; Osuga, Yutaka; Kai, Yukihiro; Nishikawa, Keisuke; Shimizu, Nobuaki; Morita, Hikaru; Plata‐Salamán, Carlos R.

doi:10.1152/ajpregu.1989.256.1.r217

Cited by 44 publications

(35 citation statements)

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“…Therefore it is likely that the difference may be derived from specific activities of haFGF and CS23. Hanai et al (1989) has reported that aFGF may participate in the regulation of feeding at the level of the central nervous system. A phasic increase of aFGF-like biological activity was detected in the cerebrospinal fluid and intracerebroventricular administration of aFGF sup- pulses at 60 Hz was significantly enhanced and LTP was generated by the injection of 40 pg/ml CS23 in both non-fasted (Fig.…”

Section: Resultsmentioning

confidence: 99%

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Effects of acidic fibroblast growth factor on higpocampal long‐term potentiation in fasted rats

Hisajima

Saito

Abe

et al. 1992

J of Neuroscience Research

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Effects of human recombinant acidic fibroblast growth factor (haFGF) on long-term potentiation (LTP) and the increase of the spike amplitude induced by weak tetanic stimulation were investigated and compared with those of CS23 (modified human basic FGF) in the dentate gyrus of fasted and nonfasted rats. haFGF didn't influence the LTP induced by the tetanus of 100 pulses at 100 Hz in both 24 hr fasted and non-fasted rats. On the other hand, the tetanus of 20 pulses at 60 Hz significantly enhanced the amplitude of population spike and facilitated the generation of LTP by the i.c.v. injection of 10 microliters of 20-40 micrograms/ml haFGF in 24 hr fasted rats but not in non-fasted rats. However, 40 micrograms/ml CS23 induced LTP when the tetanus of 20 pulses at 60 Hz was applied in both fasted and non-fasted states. These results suggest that haFGF might be one of the regulating factors of feeding and memory.

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Section: Resultsmentioning

confidence: 99%

“…It has been reported that a phasic increase of FGFlike biological activity was detected in the cerebrospinal fluid after feeding or after intraperitoneal injection of glucose (Hanai et al, 1989). It is possible that the effects of FGF on hippocampal LTP differ with feeding condition.…”

Section: Introductionmentioning

confidence: 99%

Effects of acidic fibroblast growth factor on higpocampal long‐term potentiation in fasted rats

Hisajima

Saito

Abe

et al. 1992

J of Neuroscience Research

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“…For example, fasting reduces, and refeeding increases, endogenous hypothalamic FGF expression (mRNA and protein levels), and icv-administered FGF1 or -2 decreases food intake in rats (20,40). Feeding suppression by FGF1 is associated with upregulation of c-Fos activity in periventricular astrocytes (58) and increased protein kinase C activity in glucose-sensitive neurons of the lateral hypothalamus (41).…”

Section: Discussionmentioning

confidence: 99%

“…Others have shown that intracerebroventricular (icv) injection of FGF1 or -2 decreases food intake (Refs. 20,22,40, and 41 and references therein) and that polyclonal antibodies against either ligand or FGFR1 induce weight gain (28,52).…”

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confidence: 99%

Monoclonal antibody antagonists of hypothalamic FGFR1 cause potent but reversible hypophagia and weight loss in rodents and monkeys

Sun¹,

Malabunga²,

Tonra³

et al. 2007

American Journal of Physiology-Endocrinology and Metabolism

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Leibel RL, Kussie P. Monoclonal antibody antagonists of hypothalamic FGFR1 cause potent but reversible hypophagia and weight loss in rodents and monkeys. Am J Physiol Endocrinol Metab 292: E964 -E976, 2007. First published November 28, 2006; doi:10.1152/ajpendo.00089.2006.-We generated three fully human monoclonal antibody antagonists against fibroblast growth factor receptor-1 (FGFR1) that potently block FGF signaling. We found that antibodies targeting the c-splice form of the receptor (FGFR1c) were anorexigenic when administered intraperitoneally three times weekly to mice, resulting in rapid, dose-dependent weight loss that plateaued (for doses Ͼ4 mg/kg) at 35-40% in 2 wk. Animals appeared healthy during treatment and regained their normal body weights and growth trajectories upon clearance of the antibodies from the bloodstream. Measurements of food consumption and energy expenditure indicated that the rapid weight loss was induced primarily by decreased energy intake and not by increased energy expenditure or cachexia and was accompanied by a greater reduction in fat than lean body mass. Hypophagia was not caused through malaise or illness, as indicated by absence of conditioned taste aversion, pica behavior, and decreased need-induced salt intake in rats. In support of a hypothalamic site of action, we found that, after intraperitoneal injections, anti-FGFR1c (IMC-A1), but not a control antibody, accumulated in the median eminence and adjacent mediobasal hypothalamus and that FGFR1c is enriched in the hypothalamus of mice. Furthermore, a single intracerebroventricular administration of 3 g of IMC-A1 via the 3rd ventricle to mice caused an ϳ36% reduction in food intake and an ϳ6% weight loss within the ensuing 24 h. Our data suggest that FGF signaling through FGFR1c may play a physiological role in hypothalamic feeding circuit and that blocking it leads to hypophagia and weight loss. energy homeostasis; hypothalamus; fibroblast growth factor receptor; food intake; obesity THE FGF-FGFR AXIS (fibroblast growth factor-fibroblast growth factor receptor) plays a central role in embryonic development, osteogenesis, tissue maintenance, and repair (24,42,46). FGF signaling is complex: at least 22 ligands are known that signal through four distinct cell surface receptors (FGFR1, -2, -3, and -4). Some FGF-knockouts (such as FGF4, -8, -9, -10, -18 and FGFR1) are embryonic lethal; others generate relatively mild phenotypes due to considerable redundancy in the signaling pathway(s) (10,24,42,46). Loss-of-function mutations in FGFR1 have been implicated in instances of hypogonadotropic hypogonadism (Kallmann syndrome), indicating a role for the receptor in human central nervous system (CNS)/hypothalamic development (45). FGF ligand-receptor binding induces receptor dimerization and autophosphorylation, leading to downstream activation of effector molecules such as mitogen-activating protein kinase (MAPK). In FGFR1, -2, and -3, alternative splicing of the exons encoding the third IgG-like domain produces either the b-or...

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“…Therefore, it is possible that there are different regulational mechanisms on the receptors which have different binding affini ties to aFGF and bFGF, and these two FGFs have different neurotrophic effects in the brain, although we have not done binding ex periments. On the other hand, it has been re ported that aFGF may be concerned with the regulation of feeding at the level of the central nervous system (30,31). Therefore, it is possi ble that bFGF might participate in the neuro trophic effect in the brain by binding to bFGF-sensitive receptors, and on the other hand, aFGF might participate in other effects such as feeding regulation and neurotrophic effect in the retina by binding to aFGF-sensi tive receptors.…”

Section: Discussionmentioning

confidence: 99%

Human Acidic Fibroblast Growth Factor Has Trophic Effects on Cultured Neurons from Multiple Regions of Brain and Retina.

et al. 1991

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Neurotrophic activities of human recombinant acidic fibroblast growth factor (haFGF) were evaluated on primary cultured neurons from various brain regions and compared with those of CS23, modified human basic fibroblast growth factor. Survival of cultured neurons from embryonic day 16 (E16) rat cortex and sub stantia nigra was significantly increased by the addition of more than 10 ng/ml haFGF and that from the hippocampus was increased by 100 and 1000 ng/ml. However, en hancement of viability by haFGF was observed only in 1000 ng/ml-treated neurons from the striatum, thalamus, colliculus and cerebellum; and it was not observed in septal neurons. Survival of cultured neurons from postnatal day 15 rat on glial feeder layer was significantly increased by the addition of 1000 ng/ml haFGF, except for neurons from the septum. CS23 (10 ng/ml) increased the survival of cultured neurons from all regions mentioned above, and its effects were stronger than those of 1000 ng/ml haFGF. Addition of more than 10 ng/ml haFGF significantly increased the sur vival of cultured neurons from neonatal day 2 rat retina. Addition of 1000 ng/ml haFGF increased the choline acetyl transferase activity of E16 septal neurons slightly but significantly, but didn't increase the dopamine uptake activity of embryonic day E15 ventral midbrain. These results show that haFGF is effective on limited regions and ages of brain and retina, while CS23 is effective on all regions tested.

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Central action of acidic fibroblast growth factor in feeding regulation

Cited by 44 publications

References 0 publications

Effects of acidic fibroblast growth factor on higpocampal long‐term potentiation in fasted rats

Effects of acidic fibroblast growth factor on higpocampal long‐term potentiation in fasted rats

Monoclonal antibody antagonists of hypothalamic FGFR1 cause potent but reversible hypophagia and weight loss in rodents and monkeys

Human Acidic Fibroblast Growth Factor Has Trophic Effects on Cultured Neurons from Multiple Regions of Brain and Retina.

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