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Wang B, Tang N, Chen S, Zhang X, Chen D, Li Z, Zhou B. Exploration of Appetite Regulation in Yangtze Sturgeon ( Acipenser dabryanus) During Weaning. Int J Mol Sci 2025; 26:950. [PMID: 39940719 PMCID: PMC11817240 DOI: 10.3390/ijms26030950] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2024] [Revised: 01/12/2025] [Accepted: 01/20/2025] [Indexed: 02/16/2025] Open
Abstract
Yangtze sturgeon is an endangered fish species. After weaning, some Yangtze sturgeon fry refuse to consume any food, which causes a low survival rate during the artificial breeding period. This study showed that the body length and body weight of failed weaning Yangtze sturgeons were significantly lower than those of successful weaning sturgeons. Since the brain is the center of appetite regulation, RNA-seq of the brain was employed to analyze the differentially expressed genes and their biological functions in successfully and unsuccessfully weaned fry. After that, 82,151 unigenes and 3222 DEGs were obtained. Based on the results of RNA-seq, appetite factors, including POMC, CART, NPY and AgRP, were cloned, and then a weaning experiment was designed to explore the changes in appetite after feeding a microcapsule diet (weaning group). The results showed that, during the weaning period, the expression of CART was increased on the 1st and 3rd days but decreased on the 5th, 6th, 8th and 10th days. The expression of AgRP was downregulated on the 1st and 3rd days but upregulated on the 5th, 6th, 8th and 10th days. These findings indicate that appetite was suppressed in the early and middle periods but enhanced in the latter period of weaning and that CART may play an important role in the appetite-suppressing effect.
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Affiliation(s)
- Bin Wang
- Fisheries Institute, Sichuan Academy of Agricultural Sciences, Chengdu 611731, China; (B.W.); (N.T.)
- Fish Resources and Environment in the Upper Reaches of the Yangtze River Obervation and Research Station of Sichuan Province, Yibin 644000, China
| | - Ni Tang
- Fisheries Institute, Sichuan Academy of Agricultural Sciences, Chengdu 611731, China; (B.W.); (N.T.)
- Fish Resources and Environment in the Upper Reaches of the Yangtze River Obervation and Research Station of Sichuan Province, Yibin 644000, China
- Department of Aquaculture, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China; (S.C.); (X.Z.); (D.C.)
| | - Shuhuang Chen
- Department of Aquaculture, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China; (S.C.); (X.Z.); (D.C.)
| | - Xin Zhang
- Department of Aquaculture, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China; (S.C.); (X.Z.); (D.C.)
| | - Defang Chen
- Department of Aquaculture, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China; (S.C.); (X.Z.); (D.C.)
| | - Zhiqiong Li
- Department of Aquaculture, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China; (S.C.); (X.Z.); (D.C.)
| | - Bo Zhou
- Fisheries Institute, Sichuan Academy of Agricultural Sciences, Chengdu 611731, China; (B.W.); (N.T.)
- Fish Resources and Environment in the Upper Reaches of the Yangtze River Obervation and Research Station of Sichuan Province, Yibin 644000, China
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Rahmati S, Mohammadi B, Karimi-Mehr Z, Broom DR. Effects of physical activity and exercise on Nucleobindin-2 gene expression and Nesfatin-1 concentration: A rapid review. Cell Biochem Funct 2023; 41:1016-1030. [PMID: 37909689 DOI: 10.1002/cbf.3877] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2023] [Revised: 10/11/2023] [Accepted: 10/12/2023] [Indexed: 11/03/2023]
Abstract
The aim of this rapid review is to examine the research evidence that presents the effects of physical activity and exercise on Nucleobindin-2 (NUCB2) gene expression and Nesfatin-1 concentration. Five databases (PubMed, Science Direct, Springer, Wiley, and Google Scholar) were searched for eligible studies from the earliest available date to August 2023. In human studies, Nesfatin-1 concentration either remains unchanged or increases after exercise training. It appears that higher exercise intensity and longer duration of training accentuate the increase of blood Nesfatin-1 concentration. The few human studies that have examined the acute response of exercise on Nesfatin-1 concentration from blood draws show conflicting results. There is a severe lack of biopsy studies in humans which warrants attention. All published animal studies have used the mouse model. The majority show that regular exercise training increases tissue NUCB2/Nesfatin-1. In some animal studies, where the effects of exercise on tissue Nesfatin-1 concentration has been seen as significant, there has been no significant effect of exercise on plasma Nesfatin-1 concentration. All animal studies evaluated the effect of endurance training except one which used resistance training. No animal studies have investigated the effects of acute exercise, which warrants investigation. In conclusion, human and animal studies have shown that physical training can increase NUCB2/Nesfatin-1, but research evidence examining the effect of acute exercise is in its infancy. In addition, future comparative studies are needed to compare the effects of different training protocols on NUCB2/Nesfatin-1 in humans and animals.
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Affiliation(s)
- Saleh Rahmati
- Department of Physical Education, Pardis Branch, Islamic Azad University, Pardis, Iran
- Department of Exercise Physiology, Central Tehran Branch, Islamic Azad University, Tehran, Iran
| | - Behnam Mohammadi
- Department of Exercise Physiology, Central Tehran Branch, Islamic Azad University, Tehran, Iran
| | - Zahra Karimi-Mehr
- Department of Exercise Physiology, Central Tehran Branch, Islamic Azad University, Tehran, Iran
| | - David Robert Broom
- Centre for Physical Activity, Sport and Exercise Sciences, Coventry University, Coventry, UK
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Saito S, Hashimoto H, Wakashin H, Ishibane M, Pae S, Saito S, Reien Y, Hirayama Y, Seo Y, Mizushima T, Anzai N. Central administered xenin induced Fos expression in nesfatin-1 neurons in rats. Brain Res Bull 2023; 204:110788. [PMID: 37844783 DOI: 10.1016/j.brainresbull.2023.110788] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2023] [Revised: 10/03/2023] [Accepted: 10/13/2023] [Indexed: 10/18/2023]
Abstract
Xenin is a 25-amino acid peptide identified in human gastric mucosa, which is widely expressed in peripheral and central tissues. It is known that the central or peripheral administration of xenin decreases food intake in rodents. Nesfatin-1/NUCB2 (nesfatin-1) has been identified as an anorexic neuropeptide, it is often found co-localized with many peptides in the central nervous system. After the intracerebroventricular administration of xenin on nesfain-1-like immunoreactivity (LI) neurons, we examined its effects on food intake and water intake in rats. As a result, Fos-LI neurons were observed in the organum vasculosum of the laminae terminalis (OVLT), the median preoptic nucleus (MnPO), the subfornical organ (SFO), the supraoptic nucleus (SON), the paraventricular nucleus (PVN), the arcuate nucleus (Arc), the lateral hypothalamic area (LHA), the central amygdaloid nucleus (CAN), the dorsal raphe nucleus (DR), the locus coeruleus (LC), the area postrema (AP) and the nucleus of the solitary tract (NTS). After the administration, the number of Fos-LI neurons was significantly increased in the LC and the OVLT, the MnPO, the SFO, the SON, the PVN, the Arc, the LHA, the CAN, the DR, the AP and the NTS, compared with the control group. After the administration of xenin, we conducted double immunohistochemistry for Fos and nesfatin-1, and found that the number of nesfatin-1-LI neurons expressing Fos were significantly increased in the SON, the PVN, the Arc, the LHA, the CAN, the DR, the AP and the NTS, compared with the control group. The pretreatment of nesfatin-1 antisense significantly attenuated this xenin-induced feeding suppression, while that of nesfatin-1 missense showed no improvement. These results indicate that central administered xenin may have anorexia effects associated with activated central nesfatin-1 neurons.
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Affiliation(s)
- Shota Saito
- Department of Pharmacology, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba-shi, Chiba 260-8670, JAPAN; Department of Rehabilitation, Dokkyo Medical University, 8880 Kitakobayashi, Mibu, Shimotsugagun, Tochigi 321-0293, Japan
| | - Hirofumi Hashimoto
- Department of Pharmacology, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba-shi, Chiba 260-8670, JAPAN; Department of Rehabilitation, Dokkyo Medical University, 8880 Kitakobayashi, Mibu, Shimotsugagun, Tochigi 321-0293, Japan; Department of Regulatory Physiology, Dokkyo Medical University, 880 Kitakobayashi, Mibu, Shimotsugagun, Tochigi 321-0293, Japan.
| | - Hidefumi Wakashin
- Department of Regulatory Physiology, Dokkyo Medical University, 880 Kitakobayashi, Mibu, Shimotsugagun, Tochigi 321-0293, Japan
| | - Misaki Ishibane
- Department of Pharmacology, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba-shi, Chiba 260-8670, JAPAN
| | - Sangjon Pae
- Department of Pharmacology, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba-shi, Chiba 260-8670, JAPAN
| | - Shinpei Saito
- Department of Pharmacology, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba-shi, Chiba 260-8670, JAPAN
| | - Yoshie Reien
- Department of Pharmacology, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba-shi, Chiba 260-8670, JAPAN
| | - Yuri Hirayama
- Department of Pharmacology, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba-shi, Chiba 260-8670, JAPAN
| | - Yoshiteru Seo
- Department of Regulatory Physiology, Dokkyo Medical University, 880 Kitakobayashi, Mibu, Shimotsugagun, Tochigi 321-0293, Japan; Division of Cell Structure, National Institute for Physiological Sciences, Okazaki, Aichi 444-8787, Japan
| | - Takashi Mizushima
- Department of Rehabilitation, Dokkyo Medical University, 8880 Kitakobayashi, Mibu, Shimotsugagun, Tochigi 321-0293, Japan
| | - Naohiko Anzai
- Department of Pharmacology, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba-shi, Chiba 260-8670, JAPAN
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Lin IC, Chang CH, Chong YB, Kuo SH, Cheng YW, Lieu AS, Tseng TT, Lin CJ, Tsai HP, Kwan AL. Role of Nucleobindin-2 in the Clinical Pathogenesis and Treatment Resistance of Glioblastoma. Cells 2023; 12:2420. [PMID: 37830634 PMCID: PMC10572158 DOI: 10.3390/cells12192420] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2023] [Revised: 10/03/2023] [Accepted: 10/06/2023] [Indexed: 10/14/2023] Open
Abstract
Glioblastoma (GBM) stands as the most prevalent primary malignant brain tumor, typically resulting in a median survival period of approximately thirteen to fifteen months after undergoing surgery, chemotherapy, and radiotherapy. Nucleobindin-2 (NUCB2) is a protein involved in appetite regulation and energy homeostasis. In this study, we assessed the impact of NUCB2 expression on tumor progression and prognosis of GBM. We further evaluated the relationship between NUCB2 expression and the sensitivity to chemotherapy and radiotherapy in GBM cells. Additionally, we compared the survival of mice intracranially implanted with GBM cells. High NUCB2 expression was associated with poor prognosis in patients with GBM. Knockdown of NUCB2 reduced cell viability, migration ability, and invasion ability of GBM cells. Overexpression of NUCB2 resulted in reduced apoptosis following temozolomide treatment and increased levels of DNA damage repair proteins after radiotherapy. Furthermore, mice intracranially implanted with NUCB2 knockdown GBM cells exhibited longer survival compared to the control group. NUCB2 may serve as a prognostic biomarker for poor outcomes in patients with GBM. Additionally, NUCB2 not only contributes to tumor progression but also influences the sensitivity of GBM cells to chemotherapy and radiotherapy. Therefore, targeting NUCB2 protein expression may represent a novel therapeutic approach for the treatment of GBM.
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Affiliation(s)
- I-Cheng Lin
- Department of Surgery, Kaohsiung Municipal Siaogang Hospital, Kaohsiung 81267, Taiwan;
| | - Chih-Hui Chang
- Division of Neurosurgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan; (C.-H.C.); (Y.B.C.); (A.-S.L.); (T.-T.T.)
| | - Yoon Bin Chong
- Division of Neurosurgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan; (C.-H.C.); (Y.B.C.); (A.-S.L.); (T.-T.T.)
| | - Shih-Hsun Kuo
- Department of Radiation Oncology, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan;
| | - Yu-Wen Cheng
- Gradate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan;
- Department of Neurosurgery, Kaohsiung Veterans General Hospital, Kaohsiung 81362, Taiwan
| | - Ann-Shung Lieu
- Division of Neurosurgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan; (C.-H.C.); (Y.B.C.); (A.-S.L.); (T.-T.T.)
- Department of Surgery, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80756, Taiwan
| | - Tzu-Ting Tseng
- Division of Neurosurgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan; (C.-H.C.); (Y.B.C.); (A.-S.L.); (T.-T.T.)
| | - Chien-Ju Lin
- School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 80708, Taiwan;
| | - Hung-Pei Tsai
- Division of Neurosurgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan; (C.-H.C.); (Y.B.C.); (A.-S.L.); (T.-T.T.)
| | - Aij-Lie Kwan
- Division of Neurosurgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan; (C.-H.C.); (Y.B.C.); (A.-S.L.); (T.-T.T.)
- Department of Radiation Oncology, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan;
- Department of Neurosurgery, University of Virginia, Charlottesville, VA 22904, USA
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Sun J, Gao N, Wu Q, Li Y, Zhang L, Jiang Z, Wang Z, Liu J. High plasma nesfatin-1 level in Chinese adolescents with depression. Sci Rep 2023; 13:15288. [PMID: 37714885 PMCID: PMC10504374 DOI: 10.1038/s41598-023-42513-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2022] [Accepted: 09/11/2023] [Indexed: 09/17/2023] Open
Abstract
Depression is a common psychiatric disorder with high prevalence and mortality rates as well as high risk of serious harm in adolescents that have significant negative impact on families and society. The feeding inhibitor Nesfatin-1 contributes to the regulation of stress and emotion. The purpose of this project was to compare the differences in the levels of Nesfatin-1 between adolescents with depression and healthy adolescents, and verify the association between the levels of Nesfatin-1 and severity of depression in adolescents. Adolescents with depression (n = 61) and healthy adolescents (n = 30) were evaluated. The Hamilton Depression Rating Scale (HAMD-17) was used to classify the adolescents with depression. Thirty-one and thirty-two was assigned to the mild-to-moderate (HAMD-17 ≤ 24) depression group and severe group (HAMD-17 > 24). Plasma Levels of Nesfatin-1 were measured by human ELISA Kit and differences among groups evaluated. Data were analyzed using the statistical software SPSS 23. HAMD-17 score was significantly higher in adolescents with depression than that in the healthy adolescents (P < 0.001). Median plasma Nesfatin-1 levels in adolescents with depression and healthy adolescents differed significantly at 37.3 pg/ml (22.1 pg/ml, 63.6 pg/ml) and 18.1 pg/ml (10.0 pg/ml, 25.7 pg/ml) (p < 0.001). A multivariate logistic regression analysis showed high plasma Nesfatin-1 concentrations were associated with increased risk of depression (OR = 0.914, 95% CI 0.87-0.96, P < 0.001). The receiver operating characteristic curve showed that the area under curve were 0.808 (95% CI 0.722-0.894, P < 0.001). Plasma Nesfatin-1 cut-off point of 32.45 pg/mL showed 59% sensitivity and 100% specificity. Median plasma Nesfatin-1 levels in the severe depression group (n = 30), mild-to-moderate depression group (n = 31), and control group (n = 30) were 53.4 pg/ml (28.2 pg/ml, 149.1 pg/ml), 29.9 pg/ml (14.5 pg/ml, 48.5 pg/ml) and 18.1 pg/ml (10.0 pg/ml, 25.7 pg/ml), and differed significantly among the three groups (P < 0.001). Median plasma level of Nesfatin-1 in males (n = 20) was 38.6 pg/ml (23.5 pg/ml, 70.1 pg/ml), while that in females (n = 41) was 37.3 pg/ml (22.0 pg/ml, 63.6 pg/ml), which was not a significant difference (P > 0.05). Plasma levels of Nesfatin-1 increased with severity of depression in adolescents and may be useful as a biomarker of depression severity. Further studies are needed in future projects.
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Affiliation(s)
- Jin Sun
- Department of Pediatrics, The First Affiliated Hospital of Shandong First Medical University & Shandong Province Qianfoshan Hospital, Shandong Engineering and Technology Research Center for Pediatric Drug Development, Jinan, China
| | - Nannan Gao
- Department of Pediatrics, The First Affiliated Hospital of Shandong First Medical University & Shandong Province Qianfoshan Hospital, Shandong Engineering and Technology Research Center for Pediatric Drug Development, Jinan, China
| | - Qiong Wu
- Department of Pediatrics, The First Affiliated Hospital of Shandong First Medical University & Shandong Province Qianfoshan Hospital, Shandong Engineering and Technology Research Center for Pediatric Drug Development, Jinan, China
| | - Yan Li
- Key Laboratory of Birth Regulation and Control Technology of National Health Commission of China, Maternal and Child Health Care Hospital of Shandong Province Affiliated to Qingdao University, Jinan, China
| | - Li Zhang
- Key Laboratory of Birth Regulation and Control Technology of National Health Commission of China, Maternal and Child Health Care Hospital of Shandong Province Affiliated to Qingdao University, Jinan, China
| | - Zhongliang Jiang
- Department of Psychiatry, Shandong Mental Health Center, Shandong University, Jinan, China
| | - Zhiyi Wang
- Department of Psychiatry, Shandong Mental Health Center, Shandong University, Jinan, China
| | - Jintong Liu
- Department of Pediatrics, The First Affiliated Hospital of Shandong First Medical University & Shandong Province Qianfoshan Hospital, Shandong Engineering and Technology Research Center for Pediatric Drug Development, Jinan, China.
- Department of Psychiatry, Shandong Mental Health Center, Shandong University, Jinan, China.
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Schaper SJ, Wölk E, Hofmann T, Friedrich T, Römer M, de Punder K, Rose M, Stengel A. NUCB2/nesfatin-1 in the acute stress response of obese women with high and low anxiety. Psychoneuroendocrinology 2023; 155:106325. [PMID: 37385089 DOI: 10.1016/j.psyneuen.2023.106325] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2023] [Revised: 06/20/2023] [Accepted: 06/21/2023] [Indexed: 07/01/2023]
Abstract
NUCB2/nesfatin-1 is an anorexigenic peptide hormone first known for its effects on energy homeostasis. More recently, a growing evidence suggests a role of NUCB2/nesfatin-1 in emotion regulation, particularly in the modulation of anxiety, depression and emotional stress response. Since stress-related mood disorders are often comorbid with obesity, we investigated the effect of acute psychosocial stress on circulating NUCB2/nesfatin-1 in obese women and normal-weight controls and its association with symptoms of anxiety. Forty women, 20 obese and 20 normal-weight controls, (aged between 27 and 46 years) were exposed to the Trier Social Stress Test (TSST). We assessed changes of plasma NUCB2/nesfatin-1, salivary cortisol, heart rate and subjective emotional state. Symptoms of anxiety (GAD-7), depressiveness (PHQ-9), perceived stress (PSQ-20), disordered eating (EDE-Q, EDI-2) and health-related quality of life (SF-8) were measured psychometrically. Obese women were further subdivided in a high and low anxiety group. Women with obesity displayed higher psychopathology compared to normal-weight controls. The TSST induced a biological and psychological stress response in both groups (p < 0.001). In normal-weight controls NUCB2/nesfatin-1 increased in response to stress (p = 0.011) and decreased during recovery (p < 0.050), while in obese women only the decrease during recovery was significant (p = 0.002). Obese women with high anxiety displayed higher NUCB2/nesfatin-1 levels than those in the low anxiety group (TSST: +34 %, p = 0.008; control condition: +52 %, p = 0.013). Our data substantiate the involvement of NUCB2/nesfatin-1 in the modulation of stress and anxiety. It remains unclear whether the attenuated stress response in obese subjects is due to metabolic changes or mental comorbidity.
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Affiliation(s)
- Selina Johanna Schaper
- Charité Center for Internal Medicine and Dermatology, Department for Psychosomatic Medicine, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 12203 Berlin, Germany
| | - Ellen Wölk
- Charité Center for Internal Medicine and Dermatology, Department for Psychosomatic Medicine, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 12203 Berlin, Germany
| | - Tobias Hofmann
- Charité Center for Internal Medicine and Dermatology, Department for Psychosomatic Medicine, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 12203 Berlin, Germany; Department of Psychosomatic Medicine and Psychotherapy, DRK Kliniken Berlin Wiegmann Klinik, Berlin, Germany
| | - Tiemo Friedrich
- Charité Center for Internal Medicine and Dermatology, Department for Psychosomatic Medicine, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 12203 Berlin, Germany
| | - Marthe Römer
- Charité Center for Internal Medicine and Dermatology, Department for Psychosomatic Medicine, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 12203 Berlin, Germany
| | - Karin de Punder
- Institute of Medical Psychology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany; Institute of Psychology, Department of Clinical Psychology-II, University of Innsbruck, Austria
| | - Matthias Rose
- Charité Center for Internal Medicine and Dermatology, Department for Psychosomatic Medicine, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 12203 Berlin, Germany; Department of Quantitative Health Sciences, University of Massachusetts Medical School, Worcester, MA, USA
| | - Andreas Stengel
- Charité Center for Internal Medicine and Dermatology, Department for Psychosomatic Medicine, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 12203 Berlin, Germany; Department of Psychosomatic Medicine and Psychotherapy, Medical University Hospital Tübingen, 72076 Tübingen, Germany.
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Friedrich T, Stengel A. Current state of phoenixin-the implications of the pleiotropic peptide in stress and its potential as a therapeutic target. Front Pharmacol 2023; 14:1076800. [PMID: 36860304 PMCID: PMC9968724 DOI: 10.3389/fphar.2023.1076800] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2022] [Accepted: 01/04/2023] [Indexed: 02/15/2023] Open
Abstract
Phoenixin is a pleiotropic peptide, whose known functions have broadened significantly over the last decade. Initially first described as a reproductive peptide in 2013, phoenixin is now recognized as being implicated in hypertension, neuroinflammation, pruritus, food intake, anxiety as well as stress. Due to its wide field of involvement, an interaction with physiological as well as psychological control loops has been speculated. It has shown to be both able to actively reduce anxiety as well as being influenced by external stressors. Initial rodent models have shown that central administration of phoenixin alters the behavior of the subjects when confronted with stress-inducing situations, proposing an interaction with the perception and processing of stress and anxiety. Although the research on phoenixin is still in its infancy, there are several promising insights into its functionality, which might prove to be of value in the pharmacological treatment of several psychiatric and psychosomatic illnesses such as anorexia nervosa, post-traumatic stress disorder as well as the increasingly prevalent stress-related illnesses of burnout and depression. In this review, we aim to provide an overview of the current state of knowledge of phoenixin, its interactions with physiological processes as well as focus on the recent developments in stress response and the possible novel treatment options this might entail.
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Affiliation(s)
- T. Friedrich
- Charité Center for Internal Medicine and Dermatology, Department for Psychosomatic Medicine, Charité—Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany
| | - A. Stengel
- Charité Center for Internal Medicine and Dermatology, Department for Psychosomatic Medicine, Charité—Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany,Department of Psychosomatic Medicine and Psychotherapy, University Hospital Tübingen, Tübingen, Germany,*Correspondence: A. Stengel,
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Szeliga A, Podfigurna A, Meczekalski B. Nesfatin-1 as a potential marker for functional hypothalamic amenorrhea. Gynecol Endocrinol 2022; 38:992-996. [PMID: 36150403 DOI: 10.1080/09513590.2022.2126455] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/18/2023] Open
Abstract
OBJECTIVE Nesfatin-1 plays an important role in regulating metabolism, appetite, gut motility, and eating behavior. It is suspected that abnormalities in nesfatin-1 secretion may be involved in the development of anorexia nervosa, and as such, this study aims to investigate the "circumstances of" nesfatin-1 in patients with functional hypothalamic amenorrhea (FHA). MATERIALS AND METHODS One hundred and forty-seven patients with FHA were enrolled to the present study. A control group consisting of 88 healthy, age-matched subjects was used. Both study and control groups had blood samples drawn to establish baseline serum concentrations of luteinizing hormone, follicle-stimulating hormone, estradiol, prolactin, thyroid-stimulating hormone, fT4, morning cortisol, dehydroepiandrosterone sulfate, testosterone, glucose, and insulin. Nesfatin-1 was also measured with the use of enzyme-linked immunosorbent assay. RESULTS Patients with FHA were found to have a significantly decreased concentration of serum nesfatin-1 when compared to healthy controls (6.21 ± 4.79 vs. 8.64 ± 6.63 respectively, p = 0.005). No statistically significant difference in nesfatin-1 levels was found between patients with normal and decreased BMI in the FHA group. Significant positive correlation was observed between serum nesfatin-1 concentration and 17-β-estradiol, while a significant negative correlation was observed between serum nesfatin-1 concentration and patient age, fasting glucose, and HDL levels. CONCLUSIONS This is the first known study to examine nesfatin-1 concentration in the context of clinical FHA. Patients with FHA were found to have decreased serum nesfatin-1 concentrations. This finding may prove instrumental in our future approach managing patients with FHA.
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Affiliation(s)
- Anna Szeliga
- Department of Gynecological Endocrinology, Poznan University of Medical Sciences, Poznan, Poland
| | - Agnieszka Podfigurna
- Department of Gynecological Endocrinology, Poznan University of Medical Sciences, Poznan, Poland
| | - Blazej Meczekalski
- Department of Gynecological Endocrinology, Poznan University of Medical Sciences, Poznan, Poland
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9
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Weibert E, Hofmann T, Elbelt U, Rose M, Stengel A. NUCB2/nesfatin-1 is associated with severity of eating disorder symptoms in female patients with obesity. Psychoneuroendocrinology 2022; 143:105842. [PMID: 35752057 DOI: 10.1016/j.psyneuen.2022.105842] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2022] [Revised: 06/08/2022] [Accepted: 06/14/2022] [Indexed: 10/18/2022]
Abstract
BACKGROUND Nesfatin-1 has been described as an anorexigenic peptide. Comprehensive evidence also points towards an involvement of nesfatin-1 in the modulation of emotional pathways with a sex-specific regulation of nesfatin-1 in association with anxiety. Although the implication of nesfatin-1 in the regulation of food intake is well-established in animals, data in humans are lacking. Therefore, we investigated a possible association of circulating NUCB2/nesfatin-1 with eating disorder symptoms in female and male patients displaying a wide range of body weight. METHODS We enrolled 243 inpatients (177 female, 66 male) hospitalized due to anorexia nervosa (n = 66) or obesity (n = 144) or with normal weight and suffering from somatoform, adjustment, depressive or anxiety disorders (n = 33). Plasma samples (NUCB2/nesfatin-1 levels measured by ELISA) and measures of eating disorder symptoms (by EDI-2, range 0-100) were obtained within three days after admission. RESULTS The study population displayed a distinct prevalence of eating disorder symptoms with female patients with anorexia nervosa (+ 77.0%, p < 0.001) and obesity (+ 87.9%, p < 0.001) reported significantly higher EDI-2 scores than normal weight patients of the same sex. Accordingly, males with anorexia nervosa (+ 39.7%, p < 0.05) and obesity (+ 51.7%, p < 0.001) had significantly higher EDI-2 scores than males with normal weight. Within the same BMI group, women displayed significantly higher scores than men (+ 21.4%, p < 0.05 in patients with anorexia nervosa, + 18.8%, p < 0.001 in participants with obesity). We observed a positive correlation between NUCB2/nesfatin-1 levels and EDI-2 total scores in female patients with obesity (r = 0.285, p = 0.015), whereas no associations were found in other subgroups. A positive correlation between NUCB2/nesfatin-1 levels and BMI was only observed in the male study population (r = 0.315, p = 0.018). CONCLUSIONS NUCB2/nesfatin-1 plasma levels were positively associated with EDI-2 total scores in women with obesity, while no association was observable in men. The lacking association of NUCB2/nesfatin-1 and EDI-2 total scores in female patients with anorexia nervosa might be due to already low NUCB2/nesfatin-1 plasma levels. Whether NUCB2/nesfatin-1 is selectively involved in eating behavior in women with obesity will have to be further investigated.
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Affiliation(s)
- Elena Weibert
- Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Germany; Charité Center for Internal Medicine and Dermatology, Department of Psychosomatic Medicine, Corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Germany
| | - Tobias Hofmann
- Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Germany; Charité Center for Internal Medicine and Dermatology, Department of Psychosomatic Medicine, Corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Germany
| | - Ulf Elbelt
- Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Germany; Charité Center for Internal Medicine and Dermatology, Department of Psychosomatic Medicine, Corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Germany; Division of Medicine, Department of Gastroenterology, Metabolism and Oncology, University Hospital Ruppin-Brandenburg, Brandenburg Medical School, Neuruppin, Germany; Endokrinologikum Berlin, Berlin, Germany
| | - Matthias Rose
- Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Germany; Charité Center for Internal Medicine and Dermatology, Department of Psychosomatic Medicine, Corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Germany; Quantitative Health Sciences, Outcomes Measurement Science, University of Massachusetts Medical School, Worcester, MA, USA
| | - Andreas Stengel
- Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Germany; Charité Center for Internal Medicine and Dermatology, Department of Psychosomatic Medicine, Corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Germany; Department of Psychosomatic Medicine and Psychotherapy, University Hospital Tübingen, Tübingen, Germany.
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De Felice E, Gatta C, Giaquinto D, Fioretto F, Maruccio L, d’Angelo D, Scocco P, de Girolamo P, D’Angelo L. Immunolocalization of Nesfatin-1 in the Gastrointestinal Tract of the Common Bottlenose Dolphin Tursiops truncatus. Animals (Basel) 2022; 12:ani12162148. [PMID: 36009738 PMCID: PMC9405072 DOI: 10.3390/ani12162148] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2022] [Revised: 07/25/2022] [Accepted: 08/18/2022] [Indexed: 11/17/2022] Open
Abstract
Simple Summary Nesfatin-1 (Nesf-1) is a neuropeptide that plays important roles in regulating food intake, mainly related to its anorexigenic effect, and it is mainly distributed in the digestive systems of all vertebrates. With this study, we expand knowledge on the localization of Nesf-1 in the digestive tract of an aquatic mammalian species, the common bottlenose dolphin (Tursiops truncatus), allowing comparative study on terrestrial mammals. Dolphin tissue samples (three gastric chambers and intestine) were provided by the Mediterranean Marine Mammal Tissue Bank of the Department of Comparative Biomedicine and Food Science of the University of Padova (Italy). Abstract First identified as an anorexigenic peptide, in the last decades, several studies have suggested that Nesfatin-1 (Nesf-1) is a pleiotropic hormone implicated in numerous regulatory processes in peripheral organs and tissues. In vertebrates, Nesf-1 is indeed expressed in the central nervous system and peripheral organs. In this study, we characterized the pattern of Nesf-1 distribution within the digestive tract of the common bottlenose dolphin (Tursiops truncatus), composed of three gastric chambers and an intestine without a clear subdivision in the small and large intestine, also lacking a caecum. Our results indicated that Nesf-1 is widely distributed in cells of the mucosal epithelium of the gastric chambers. Most of the immunoreactivity was observed in the second chamber, compared to the first and third chambers. Immunopositivity was also found in nerve fibers and neurons, scattered or/and clustered in ganglion structures along all the examined gastrointestinal tracts. These observations add new data on the highly conserved role of Nesf-1 in the mammalian digestive system.
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Affiliation(s)
- Elena De Felice
- School of Biosciences and Veterinary Medicine, University of Camerino, Via Gentile III da Varano, 62032 Camerino, Italy
- Correspondence:
| | - Claudia Gatta
- Department of Veterinary Medicine and Animal Production, University of Naples Federico II, Via F. Delpino 1, 80137 Naples, Italy
| | - Daniela Giaquinto
- Department of Veterinary Medicine and Animal Production, University of Naples Federico II, Via F. Delpino 1, 80137 Naples, Italy
| | - Federica Fioretto
- School of Biosciences and Veterinary Medicine, University of Camerino, Via Gentile III da Varano, 62032 Camerino, Italy
| | - Lucianna Maruccio
- Department of Veterinary Medicine and Animal Production, University of Naples Federico II, Via F. Delpino 1, 80137 Naples, Italy
| | - Danila d’Angelo
- Department of Veterinary Medicine and Animal Production, University of Naples Federico II, Via F. Delpino 1, 80137 Naples, Italy
| | - Paola Scocco
- School of Biosciences and Veterinary Medicine, University of Camerino, Via Gentile III da Varano, 62032 Camerino, Italy
| | - Paolo de Girolamo
- Department of Veterinary Medicine and Animal Production, University of Naples Federico II, Via F. Delpino 1, 80137 Naples, Italy
| | - Livia D’Angelo
- Department of Veterinary Medicine and Animal Production, University of Naples Federico II, Via F. Delpino 1, 80137 Naples, Italy
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Lu Z, Cui D, Liu JYH, Jiang B, Ngan MP, Sakata I, Takemi S, Sakai T, Lin G, Chan SW, Rudd JA. The Actions of Centrally Administered Nesfatin-1 on Emesis, Feeding, and Locomotor Activity in Suncus murinus (House Musk Shrew). Front Pharmacol 2022; 13:858522. [PMID: 35462894 PMCID: PMC9019301 DOI: 10.3389/fphar.2022.858522] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2022] [Accepted: 03/15/2022] [Indexed: 11/13/2022] Open
Abstract
Nesfatin-1 is an anorectic peptide expressed in both peripheral tissues and brain areas involved in the regulation of feeding, emotion and emesis. The aim of the present study is to characterize the distribution of NUCB2/nesfatin-1 in Suncus murinus and to investigate the actions of nesfatin-1 to affect gastrointestinal contractility, emesis, food and water intake, and locomotor activity. The deduced amino acid sequence of S. murinus nesfatin-1 using in silico cloning showed high homology with humans and rodents. NUCB2 mRNA was detected throughout the entire brain and in the gastrointestinal tract, including the stomach and gut. Western blot analysis and immunohistochemistry confirmed the expression of nesfatin-1 protein in these regions. The NUCB2 mRNA levels in the hypothalamus, hippocampus and brainstem were significantly decreased, whereas that in the striatum were increased after 24 h starvation compared to ad libitum-fed animals (p < 0.05). In in vitro studies, nesfatin-1 (0.3–1,000 pM) failed to contract or relax the isolated gastric antrum and intestinal segments. In conscious, freely moving animals, intracerebroventricular administration of nesfatin-1 (1–50 pmol) induced emesis (p < 0.05) and suppressed 6-h cumulative food intake (p < 0.05), without affecting the latency to feeding. Nesfatin-1 (25 pmol, i.c.v.) decreased 24-h cumulative food and water intake by 28.3 and 35.4%, respectively (p < 0.01). No significant differences in locomotor activity were observed. In conclusion, NUCB2/nesfatin-1 might be a potent regulator of feeding and emesis in S. murinus. Further studies are required to elucidate the mechanism of actions of this peptide as a mediator linking the brainstem NUCB2/nesfatin-1 to forebrain system.
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Affiliation(s)
- Zengbing Lu
- School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, China
- School of Health Sciences, Caritas Institute of Higher Education, Hong Kong, Hong Kong SAR, China
| | - Dexuan Cui
- School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, China
| | - Julia Yuen Hang Liu
- School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, China
| | - Bin Jiang
- School of Health Sciences, Caritas Institute of Higher Education, Hong Kong, Hong Kong SAR, China
| | - Man Piu Ngan
- School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, China
| | - Ichiro Sakata
- Graduate School of Science and Engineering, Saitama University, Saitama, Japan
| | - Shota Takemi
- Graduate School of Science and Engineering, Saitama University, Saitama, Japan
| | - Takafumi Sakai
- Graduate School of Science and Engineering, Saitama University, Saitama, Japan
| | - Ge Lin
- School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, China
| | - Sze Wa Chan
- School of Health Sciences, Caritas Institute of Higher Education, Hong Kong, Hong Kong SAR, China
- *Correspondence: Sze Wa Chan,
| | - John A. Rudd
- School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, China
- The Laboratory Animal Services Centre, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, China
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Chen X, Dong J, Jiao Q, Du X, Bi M, Jiang H. "Sibling" battle or harmony: crosstalk between nesfatin-1 and ghrelin. Cell Mol Life Sci 2022; 79:169. [PMID: 35239020 PMCID: PMC11072372 DOI: 10.1007/s00018-022-04193-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2021] [Revised: 02/02/2022] [Accepted: 02/04/2022] [Indexed: 12/17/2022]
Abstract
Ghrelin was first identified as an endogenous ligand of the growth hormone secretagogue receptor (GHSR) in 1999, with the function of stimulating the release of growth hormone (GH), while nesfatin-1 was identified in 2006. Both peptides are secreted by the same kind of endocrine cells, X/A-like cells in the stomach. Compared with ghrelin, nesfatin-1 exerts opposite effects on energy metabolism, glucose metabolism, gastrointestinal functions and regulation of blood pressure, but exerts similar effects on anti-inflammation and neuroprotection. Up to now, nesfatin-1 remains as an orphan ligand because its receptor has not been identified. Several studies have shown the effects of nesfatin-1 are dependent on the receptor of ghrelin. We herein compare the effects of nesfatin-1 and ghrelin in several aspects and explore the possibility of their interactions.
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Affiliation(s)
- Xi Chen
- Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders and State Key Disciplines: Physiology, School of Basic Medicine, Qingdao University, Qingdao, 266071, People's Republic of China
| | - Jing Dong
- Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders and State Key Disciplines: Physiology, School of Basic Medicine, Qingdao University, Qingdao, 266071, People's Republic of China
| | - Qian Jiao
- Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders and State Key Disciplines: Physiology, School of Basic Medicine, Qingdao University, Qingdao, 266071, People's Republic of China
| | - Xixun Du
- Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders and State Key Disciplines: Physiology, School of Basic Medicine, Qingdao University, Qingdao, 266071, People's Republic of China
| | - Mingxia Bi
- Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders and State Key Disciplines: Physiology, School of Basic Medicine, Qingdao University, Qingdao, 266071, People's Republic of China
| | - Hong Jiang
- Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders and State Key Disciplines: Physiology, School of Basic Medicine, Qingdao University, Qingdao, 266071, People's Republic of China.
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13
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Dotania K, Tripathy M, Rai U. A comparative account of nesfatin-1 in vertebrates. Gen Comp Endocrinol 2021; 312:113874. [PMID: 34331938 DOI: 10.1016/j.ygcen.2021.113874] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2021] [Revised: 07/14/2021] [Accepted: 07/25/2021] [Indexed: 12/17/2022]
Abstract
Nesfatin-1 was discovered as an anorexigenic peptide derived from proteolytic cleavage of the prepropeptide, nucleobindin 2 (NUCB2). It is widely expressed in central as well as peripheral tissues and is known to have pleiotropic effects such as regulation of feeding, reproduction, cardiovascular functions and maintenance of glucose homeostasis. In order to execute its multifaceted role, nesfatin-1 employs diverse signaling pathways though its receptor has not been identified till date. Further, nesfatin-1 is reported to be under the regulatory effect of feeding state, nutritional status as well as several metabolic and reproductive hormones. This peptide has also been associated with variety of human diseases, especially metabolic, reproductive, cardiovascular and mental disorders. The current review is aimed to present a consolidated picture and highlight lacunae for further investigation in order to develop a deeper comprehensive understanding on physiological significance of nesfatin-1 in vertebrates.
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Affiliation(s)
| | - Mamta Tripathy
- Department of Zoology, Kalindi College, University of Delhi, Delhi 110008, India
| | - Umesh Rai
- Department of Zoology, University of Delhi, Delhi 110007, India.
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14
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Role of the Novel Peptide Phoenixin in Stress Response and Possible Interactions with Nesfatin-1. Int J Mol Sci 2021; 22:ijms22179156. [PMID: 34502065 PMCID: PMC8431171 DOI: 10.3390/ijms22179156] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2021] [Revised: 08/16/2021] [Accepted: 08/18/2021] [Indexed: 12/23/2022] Open
Abstract
The novel peptide phoenixin was shown to be involved in several physiological processes ranging from reproduction to food intake. Interest in this protein has steadily increased over the last few years and its known implications have become much broader, playing a role in glucose homeostasis, anxiety, nociception, and pruritus. Phoenixin is expressed in a multitude of organs such as the small intestine, pancreas, and in the hypothalamus, as well as several other brain nuclei influencing numerous physiological functions. Its highly conserved amino-acid sequence amongst species leads to the assumption, that phoenixin might be involved in essential physiological functions. Its co-expression and opposing functionality to the extensively studied peptide nesfatin-1 has given rise to the idea of a possible counterbalancing role. Several recent publications focused on phoenixin’s role in stress reactions, namely restraint stress and lipopolysaccharide-induced inflammation response, in which also nesfatin-1 is known to be altered. This review provides an overview on the phoenixins and nesfatin-1 properties and putative effects, and especially highlights the recent developments on their role and interaction in the response to response.
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15
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Kmiecik AM, Dzięgiel P, Podhorska-Okołów M. Nucleobindin-2/Nesfatin-1-A New Cancer Related Molecule? Int J Mol Sci 2021; 22:ijms22158313. [PMID: 34361082 PMCID: PMC8348729 DOI: 10.3390/ijms22158313] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2021] [Revised: 07/29/2021] [Accepted: 07/29/2021] [Indexed: 01/03/2023] Open
Abstract
Cancer is a heterogeneous disease, and even tumors with similar clinicopathological characteristics show different biology, behavior, and treatment responses. As a result, there is an urgent need to define new prognostic and predictive markers to make treatment options more personalized. According to the latest findings, nucleobindin-2/nesfatin-1 (NUCB2/NESF-1) is an important factor in cancer development and progression. Nucleobindin-2 is a precursor protein of nesfatin-1. As NUCB2 and nesfatin-1 are colocalized in each tissue, their expression is often analyzed together as NUCB2. The metabolic function of NUCB2/NESF-1 is related to food intake, glucose metabolism, and the regulation of immune, cardiovascular and endocrine systems. Recently, it has been demonstrated that high expression of NUCB2/NESF-1 is associated with poor outcomes and promotes cell proliferation, migration, and invasion in, e.g., breast, colon, prostate, endometrial, thyroid, bladder cancers, or glioblastoma. Interestingly, nesfatin-1 is also considered an inhibitor of the proliferation of human adrenocortical carcinoma and ovarian epithelial carcinoma cells. These conflicting results make NUCB2/NESF-1 an interesting target of study in the context of cancer progression. The present review is the first to describe NUCB2/NESF-1 as a new prognostic and predictive marker in cancers.
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Affiliation(s)
- Alicja M. Kmiecik
- Division of Histology and Embryology, Department of Human Morphology and Embryology, Wroclaw Medical University, 50-368 Wroclaw, Poland;
- Correspondence: ; Tel.: +48-7-1784-1365; Fax: +48-7-1784-0082
| | - Piotr Dzięgiel
- Division of Histology and Embryology, Department of Human Morphology and Embryology, Wroclaw Medical University, 50-368 Wroclaw, Poland;
- Department of Physiotherapy, University School of Physical Education, 51-612 Wroclaw, Poland
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16
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Özdemir-Kumral ZN, Koyuncuoğlu T, Arabacı-Tamer S, Çilingir-Kaya ÖT, Köroğlu AK, Yüksel M, Yeğen BÇ. High-fat Diet Enhances Gastric Contractility, but Abolishes Nesfatin-1-induced Inhibition of Gastric Emptying. J Neurogastroenterol Motil 2021; 27:265-278. [PMID: 33795544 PMCID: PMC8026381 DOI: 10.5056/jnm20206] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2020] [Accepted: 10/30/2020] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND/AIMS Gastrointestinal motility changes contribute to development and maintenance of obesity. Nesfatin-1 (NES-1) is involved in central appetite control. The aim is to elucidate effects of NES-1 and high-fat diet (HFD) on gastrointestinal motility and to explore myenteric neuron expressions of tyrosine hydroxylase (TH), vasoactive intestinal peptide (VIP), and neuronal nitric oxide synthase (nNOS) in HFDinduced oxidative injury. METHODS Sprague-Dawley rats were fed with normal diet (ND) or HFD. Gastric emptying rate was measured following NES-1 (5 pmol/rat, intracerebroventricular) preceded by subcutaneous injections of glucagon-like peptide 1 (GLP-1), cholecystokinin 1 (CCK-1), and gastrin/CCK-2 receptor antagonists. In carbachol-contracted gastric and ileal strips, contractile changes were recorded by adding NES- 1 (0.3 nmol/L), GLP-1, CCK-1, and gastrin/CCK-2 antagonists. RESULTS Neither HFD nor NES-1 changed methylcellulose emptying, but NES-1 delayed saline emptying in cannulated ND-rats. Inhibitory effect of NES-1 on gastric emptying in ND-rats was reversed by all antagonists, and abolished in HFD-rats. In HFD-rats, carbachol-induced contractility was enhanced in gastric, but inhibited in ileal strips. HFD increased body weight, while serum triglycerides, alanine transaminase, aspartate aminotransferase, glucose, and levels of malondialdehyde, glutathione, myeloperoxidase activity, and luminolchemiluminescence in hepatic, ileal, and adipose tissues were similar in ND- and HFD-rats, but only lucigenin-chemiluminescence was increased in HFD-rats. Vasoactive intestinal peptide (VIP) and TH immunoreactivities were depressed and nNOS immunoreactivity was increased in gastric tissues of HFD-rats, while VIP and TH were enhanced, but nNOS was reduced in their intestines. CONCLUSIONS HFD caused mild systemic inflammation, disrupted enteric innervation, enhanced gastric contractility, inhibited ileal contractility, and eliminated inhibitory effect of NES-1 on gastric motility.
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Affiliation(s)
| | - Türkan Koyuncuoğlu
- Departments of Physiology, Marmara University School of Medicine, Istanbul, Turkey
| | - Sevil Arabacı-Tamer
- Departments of Physiology, Marmara University School of Medicine, Istanbul, Turkey
| | - Özlem T Çilingir-Kaya
- Departments of Histology and Embryology, Marmara University School of Medicine, Istanbul, Turkey
| | - Ayça K Köroğlu
- Departments of Histology and Embryology, Marmara University School of Medicine, Istanbul, Turkey
- Department of Histology and Embryology, Istinye University Faculty of Medicine; Istanbul, Turkey
| | - Meral Yüksel
- Marmara University Vocational School of Health Sciences, Istanbul, Turkey
| | - Berrak Ç Yeğen
- Departments of Physiology, Marmara University School of Medicine, Istanbul, Turkey
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Schalla MA, Taché Y, Stengel A. Neuroendocrine Peptides of the Gut and Their Role in the Regulation of Food Intake. Compr Physiol 2021; 11:1679-1730. [PMID: 33792904 DOI: 10.1002/cphy.c200007] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
The regulation of food intake encompasses complex interplays between the gut and the brain. Among them, the gastrointestinal tract releases different peptides that communicate the metabolic state to specific nuclei in the hindbrain and the hypothalamus. The present overview gives emphasis on seven peptides that are produced by and secreted from specialized enteroendocrine cells along the gastrointestinal tract in relation with the nutritional status. These established modulators of feeding are ghrelin and nesfatin-1 secreted from gastric X/A-like cells, cholecystokinin (CCK) secreted from duodenal I-cells, glucagon-like peptide 1 (GLP-1), oxyntomodulin, and peptide YY (PYY) secreted from intestinal L-cells and uroguanylin (UGN) released from enterochromaffin (EC) cells. © 2021 American Physiological Society. Compr Physiol 11:1679-1730, 2021.
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Affiliation(s)
- Martha A Schalla
- Charité Center for Internal Medicine and Dermatology, Department for Psychosomatic Medicine, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany
| | - Yvette Taché
- Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, CURE: Digestive Diseases Research Center, David Geffen School of Medicine, UCLA, Los Angeles, California, USA.,VA Greater Los Angeles Healthcare System, Los Angeles, California, USA
| | - Andreas Stengel
- Charité Center for Internal Medicine and Dermatology, Department for Psychosomatic Medicine, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany.,Department of Psychosomatic Medicine and Psychotherapy, Medical University Hospital Tübingen, Tübingen, Germany
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18
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Chen H, Li X, Ma H, Zheng W, Shen X. Reduction in Nesfatin-1 Levels in the Cerebrospinal Fluid and Increased Nigrostriatal Degeneration Following Ventricular Administration of Anti-nesfatin-1 Antibody in Mice. Front Neurosci 2021; 15:621173. [PMID: 33613183 PMCID: PMC7890421 DOI: 10.3389/fnins.2021.621173] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2020] [Accepted: 01/11/2021] [Indexed: 12/19/2022] Open
Abstract
Nesfatin-1 is one of several brain-gut peptides that have a close relationship with the central dopaminergic system. Our previous studies have shown that nesfatin-1 is capable of protecting nigral dopaminergic neurons against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity. A recent study also revealed a reduced blood level of nesfatin-1 in patients with Parkinson’s disease (PD). The current study was designed to investigate whether reduced nesfatin-1 in cerebrospinal fluid (CSF) induces nigrostriatal system degeneration. An intra-cerebroventricular (ICV) injection technique was used to administer anti-nesfatin-1 antibody directly into the lateral ventricle of the brain. Enzyme-linked immunosorbent assay (ELISA) results showed that ICV injection of anti-nesfatin-1 antibody into the lateral ventricle of the brain once daily for 2 weeks caused a significant reduction in nesfatin-1 levels in the CSF (93.1%). Treatment with anti-nesfatin-1 antibody resulted in a substantial loss (23%) of TH-positive (TH+) dopaminergic neurons in the substantia nigra pars compacta (SNpc), as shown by immunofluorescence staining, a depletion in dopamine and its metabolites in the striatum detected by high-performance liquid chromatography (HPLC), and obvious nuclear shrinkage and mitochondrial lesions in dopaminergic neurons in the SNpc detected by transmission electron microscopy (TEM). Furthermore, the results from our Western blot and ELISA experiments demonstrated that anti-nesfatin-1 antibody injection induced an upregulation of caspase-3 activation, increased the expression of p-ERK, and elevated brain-derived neurotrophic factor (BDNF) levels in the SNpc. Taken together, these observations suggest that reduced nesfatin-1 in the brain may induce nigrostriatal dopaminergic system degeneration; this effect may be mediated via mitochondrial dysfunction-related apoptosis. Our data support a role of nesfatin-1 in maintaining the normal physiological function of the nigrostriatal dopaminergic system.
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Affiliation(s)
- Huanhuan Chen
- Department of Epidemiology and Health Statistics, Medical School of Qingdao University, Qingdao, China
| | - Xuelian Li
- Department of Epidemiology and Health Statistics, Medical School of Qingdao University, Qingdao, China
| | - Hui Ma
- Department of Epidemiology and Health Statistics, Medical School of Qingdao University, Qingdao, China
| | - Wei Zheng
- School of Health Sciences, Purdue University, West Lafayette, IN, United States
| | - Xiaoli Shen
- Department of Epidemiology and Health Statistics, Medical School of Qingdao University, Qingdao, China.,School of Health Sciences, Purdue University, West Lafayette, IN, United States
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19
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Rupp SK, Wölk E, Stengel A. Nesfatin-1 Receptor: Distribution, Signaling and Increasing Evidence for a G Protein-Coupled Receptor - A Systematic Review. Front Endocrinol (Lausanne) 2021; 12:740174. [PMID: 34566899 PMCID: PMC8461182 DOI: 10.3389/fendo.2021.740174] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2021] [Accepted: 08/26/2021] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND Nesfatin-1 is an 82-amino acid polypeptide, cleaved from the 396-amino acid precursor protein nucleobindin-2 (NUCB2) and discovered in 2006 in the rat hypothalamus. In contrast to the growing body of evidence for the pleiotropic effects of the peptide, the receptor mediating these effects and the exact signaling cascades remain still unknown. METHODS This systematic review was conducted using a search in the Embase, PubMed, and Web of Science databases. The keywords "nesfatin-1" combined with "receptor", "signaling", "distribution", "pathway", g- protein coupled receptor", and "binding" were used to identify all relevant articles reporting about potential nesfatin-1 signaling and the assumed mediation via a Gi protein-coupled receptor. RESULTS Finally, 1,147 articles were found, of which 1,077 were excluded in several steps of screening, 70 articles were included in this systematic review. Inclusion criteria were studies investigating nesfatin-1's putative receptor or signaling cascade, observational preclinical and clinical studies, experimental studies, registry-based studies, cohort studies, population-based studies, and studies in English language. After screening for eligibility, the studies were assigned to the following subtopics and discussed regarding intracellular signaling of nesfatin-1 including the potential receptor mediating these effects and downstream signaling of the peptide. CONCLUSION The present review sheds light on the various effects of nesfatin-1 by influencing several intracellular signaling pathways and downstream cascades, including the peptide's influence on various hormones and their receptors. These data point towards mediation via a Gi protein-coupled receptor. Nonetheless, the identification of the nesfatin-1 receptor will enable us to better investigate the exact mediating mechanisms underlying the different effects of the peptide along with the development of agonists and antagonists.
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Affiliation(s)
- Sophia Kristina Rupp
- Department of Psychosomatic Medicine and Psychotherapy, University Hospital Tübingen, Tübingen, Germany
| | - Ellen Wölk
- Charité Center for Internal Medicine and Dermatology, Department for Psychosomatic Medicine, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany
| | - Andreas Stengel
- Department of Psychosomatic Medicine and Psychotherapy, University Hospital Tübingen, Tübingen, Germany
- Charité Center for Internal Medicine and Dermatology, Department for Psychosomatic Medicine, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany
- *Correspondence: Andreas Stengel,
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20
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Canosa LF, Bertucci JI. Nutrient regulation of somatic growth in teleost fish. The interaction between somatic growth, feeding and metabolism. Mol Cell Endocrinol 2020; 518:111029. [PMID: 32941926 DOI: 10.1016/j.mce.2020.111029] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2020] [Revised: 07/03/2020] [Accepted: 09/07/2020] [Indexed: 12/13/2022]
Abstract
This review covers the current knowledge on the regulation of the somatic growth axis and its interaction with metabolism and feeding regulation. The main endocrine and neuroendocrine factors regulating both the growth axis and feeding behavior will be briefly summarized. Recently discovered neuropeptides and peptide hormones will be mentioned in relation to feeding control as well as growth hormone regulation. In addition, the influence of nutrient and nutrient sensing mechanisms on growth axis will be highlighted. We expect that in this process gaps of knowledge will be exposed, stimulating future research in those areas.
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Affiliation(s)
- Luis Fabián Canosa
- Instituto Tecnológico de Chascomús (INTECH), CONICET-UNSAM, Chascomús, Buenos Aires, Argentina.
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21
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Yuan D, Zhang X, Wang B, Tang T, Lei L, Deng X, Zhou C, Li Z. Effects of feeding status on nucb1 and nucb2A mRNA expression in the hypothalamus of Schizothorax davidi. FISH PHYSIOLOGY AND BIOCHEMISTRY 2020; 46:1139-1154. [PMID: 32130563 DOI: 10.1007/s10695-020-00780-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/23/2019] [Accepted: 02/20/2020] [Indexed: 06/10/2023]
Abstract
NUCB1 and NUCB2, two novel nucleobindins, have attracted extensive attention for their role in the appetite regulation in mammals. However, little is known about the appetite regulation of NUCB1 and NUCB2 in fish species. Therefore, we investigated the role of these peptides in the regulation of feeding in Schizothorax davidi (S. davidi). In this study, full-length cDNA sequences of nucb1 and nucb2A of S. davidi were obtained for the first time. Additionally, the tissue distribution and the effects of different energy status on nucb1 and nucb2A mRNAs abundance were assessed, showing that nucb1 and nucb2A are widely distributed in 18 detected tissues, with the highest expression in the cerebellum. The abundances of nucb1 and nucb2A increased in the hypothalamus at 1 h and 3 h post-feeding. Furthermore, fasting and re-feeding experiments showed that the expressions of nucb1 and nucb2A in hypothalamus significantly decreased after fasting for 7 days, and returned to the control level after re-feeding for 3 or 5 days. In conclusion, the present study suggests that both NUCB1 and NUCB2A are involved in the short-term and long-term appetite regulation, as an anorexigenic factor, in S. davidi. These results can provide a basis for further investigation into the appetite regulatory role of NUCB family in teleost.
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Affiliation(s)
- Dengyue Yuan
- Key Laboratory of Freshwater Fish Reproduction and Development (Ministry of Education), Key Laboratory of Aquatic Science of Chongqing, School of Life Sciences, Southwest University, Chongqing, China.
| | - Xin Zhang
- The Key Laboratory of Mariculture, Ministry of Education, Fisheries College, Ocean University of China, Qingdao, Shandong, China
| | - Bin Wang
- The Department of Aquaculture, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, Sichuan, China
| | - Tao Tang
- The Department of Aquaculture, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, Sichuan, China
| | - Luo Lei
- The Department of Aquaculture, College of Animal Science, Southwest University, Chongqing, China
| | - Xingxing Deng
- The Department of Aquaculture, College of Animal Science, Southwest University, Chongqing, China
| | - Chaowei Zhou
- The Department of Aquaculture, College of Animal Science, Southwest University, Chongqing, China
| | - Zhiqiong Li
- The Department of Aquaculture, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, Sichuan, China
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22
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Schalla MA, Unniappan S, Lambrecht NWG, Mori M, Taché Y, Stengel A. NUCB2/nesfatin-1 - Inhibitory effects on food intake, body weight and metabolism. Peptides 2020; 128:170308. [PMID: 32229144 DOI: 10.1016/j.peptides.2020.170308] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2019] [Revised: 02/17/2020] [Accepted: 03/20/2020] [Indexed: 02/06/2023]
Abstract
Since its discovery in 2006 by Oh-I and colleagues, NUCB2/nesfatin-1 encoded by nucleobindin-2 (NUCB2) has drawn sustained attention as reflected in over 500 publications. Among those, more than half focused on the alterations of food intake, body weight and metabolism (glucose, fat) induced by nesfatin-1 and/or NUCB2/nesfatin-1. In the current review we discuss the existing literature focusing on NUCB2/nesfatin-1's influence on food intake, body weight and glucose as well as fat metabolism and highlight gaps in knowledge.
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Affiliation(s)
- Martha A Schalla
- Charité Center for Internal Medicine and Dermatology, Department for Psychosomatic Medicine, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany
| | - Suraj Unniappan
- Laboratory of Integrative Neuroendocrinology, Department of Veterinary Biomedical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK, Canada
| | - Nils W G Lambrecht
- Department of Pathology and Laboratory Medicine, VA Medical Center, Long Beach, California, USA
| | - Masatomo Mori
- Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, Japan
| | - Yvette Taché
- VA Greater Los Angeles Healthcare System, Los Angeles, California, USA; Department of Medicine, CURE: Digestive Diseases Research Center, Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine, UCLA, Los Angeles, California, USA
| | - Andreas Stengel
- Charité Center for Internal Medicine and Dermatology, Department for Psychosomatic Medicine, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany; Department of Psychosomatic Medicine and Psychotherapy, Medical University Hospital Tübingen, Tübingen, Germany.
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23
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Angelone T, Rocca C, Pasqua T. Nesfatin-1 in cardiovascular orchestration: From bench to bedside. Pharmacol Res 2020; 156:104766. [PMID: 32201244 DOI: 10.1016/j.phrs.2020.104766] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2020] [Revised: 03/09/2020] [Accepted: 03/18/2020] [Indexed: 12/11/2022]
Abstract
Since the discovery of Nesfatin-1 in 2006, intensive research was finalized to further and deeper investigate the precise physiological functions of the peptide at both central and peripheral levels, rapidly enriching the knowledge regarding this intriguing molecule. Nesfatin-1 is a hypothalamic peptide generated via the post-translational processing of its precursor Nucleobindin 2, a protein supposed to play a role in many biological processes thanks to its ability to bind calcium and to interact with different intracellular proteins. Nesfatin-1 is mainly known for its anorexic properties, but it also controls water intake and glucose homeostasis. Recent experimental evidences describe the peptide as a possible direct/indirect orchestrator of central and peripheral cardiovascular control. A specific Nesfatin-1 receptor still remains to be identified although numerous studies suggest that the peptide activates extra- and intracellular regulatory pathways by involving several putative binding sites. The present paper was designed to systematically review the latest findings about Nesfatin-1, focusing on its cardiovascular regulatory properties under normal and physiopathological conditions. The hope is to provide the conceptual basis to consider Nesfatin-1 not only as a pleiotropic neuroendocrine molecule, but also as a homeostatic modulator of the cardiovascular function and with a crucial role in cardiovascular diseases.
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Affiliation(s)
- Tommaso Angelone
- Laboratory of Cellular and Molecular Cardiovascular Patho-physiology, Dept of Biology, Ecology and Earth Sciences, University of Calabria, Rende, CS, Italy; National Institute of Cardiovascular Research I.N.R.C., Bologna, Italy.
| | - Carmine Rocca
- Laboratory of Cellular and Molecular Cardiovascular Patho-physiology, Dept of Biology, Ecology and Earth Sciences, University of Calabria, Rende, CS, Italy
| | - Teresa Pasqua
- Laboratory of Cellular and Molecular Cardiovascular Patho-physiology, Dept of Biology, Ecology and Earth Sciences, University of Calabria, Rende, CS, Italy.
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24
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Güneş H, Alkan Baylan F, Güneş H, Temiz F. Can Nesfatin-1 Predict Hypertension in Obese Children? J Clin Res Pediatr Endocrinol 2020; 12:29-36. [PMID: 31339256 PMCID: PMC7127895 DOI: 10.4274/jcrpe.galenos.2019.2019.0072] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2019] [Accepted: 07/17/2019] [Indexed: 12/01/2022] Open
Abstract
Objective The prevalence of childhood obesity is increasing and leads to co-morbidities such as hypertension. However, it is still not clear why some obese individuals are hypertensive and others not. Nesfatin-1 is a recently discovered anorexigenic peptide which also has effects on blood pressure (BP). Our aim was to evaluate the relationship between obesity-related hypertension and Nesfatin-1. Methods This cross-sectional study comprised 87 obese children. The patients were divided into two groups; hypertensive (n=30) and normotensive (n=57) obese. The American Academy of Pediatrics guidelines were used to diagnose hypertension. Blood samples were collected after 12 hours of fasting to investigate Nesfatin-1 concentrations. We also evaluated serum trace elements in addition to the routine blood tests. Results Body mass index (BMI), weight and serum Nesfatin-1 concentrations were higher in the hypertensive group (p=0.002, p=0.001, and p=0.007, respectively). There was no difference between serum zinc levels, but Copper (Cu) levels were significantly lower in the hypertensive group (p=0.248, p=0.007, respectively). There were positive correlations between BP and BMI and weight Z-scores and a negative correlation with Cu. The optimal cut-off value of Nesfatin-1 to predict hypertension was found to be >1.8 ng/mL, with a specificity of 71.9% and a sensitivity of 96.7% [area under the curve=0.703, 95% confidence interval (CI): 0.577-0.809; p=0.002]. In multiple logistic regression analysis Nesfatin-1 [Odds ratio (OR)=1.103, 95% CI: 1.039-1.171; p=0.001], Cu (OR=0.947, 95% CI: 0.915-0.979; p=0.001) and BMI for age Z-score (OR=56.277, 95% CI: 5.791-546.907; p=0.001) still remained significant predictors of hypertension. Conclusion Nesfatin-1 levels are higher and are an independent predictor of hypertension in obese subjects.
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Affiliation(s)
- Hatice Güneş
- Sütçü İmam University Faculty of Medicine, Department of Pediatrics, Kahramanmaraş, Turkey
| | - Filiz Alkan Baylan
- Sütçü İmam University Faculty of Medicine, Department of Biochemistry, Kahramanmaraş, Turkey
| | - Hakan Güneş
- Sütçü İmam University Faculty of Medicine, Department of Cardiology, Kahramanmaraş, Turkey
| | - Fatih Temiz
- Sütçü İmam University Faculty of Medicine, Department of Pediatric Endocrinology and Metabolism, Kahramanmaraş, Turkey
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25
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de Dios O, Herrero L, Gavela-Pérez T, Soriano-Guillén L, Garcés C. Sex-specific association of plasma nesfatin-1 concentrations with obesity in children. Pediatr Obes 2019; 14:e12567. [PMID: 31507101 DOI: 10.1111/ijpo.12567] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2019] [Revised: 05/31/2019] [Accepted: 07/05/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND Nesfatin-1, an anorexigenic peptide, has been associated with food intake and thermogenesis, with discordant findings in humans and scarce studies in children to date. OBJECTIVES The aim of this study was to analyze the relationship of obesity with nesfatin-1 levels in two cohorts of children. METHODS Plasma nesfatin-1 concentrations were analyzed in 6- to 9-year-olds (n = 140) and 12- to 16-year-old children (n = 96), including children with obesity and their sex- and age-matched normal-weight counterparts. Anthropometric measurements were assessed. Cholesterol and triglycerides were determined enzymatically, insulin concentrations were measured by radioimmunoassay using a commercial kit and nesfatin-1, leptin and hs-CRP concentrations were determined using commercial ELISA kits. RESULTS Nesfatin-1 concentrations were significantly lower in younger (P = .001) and older (P = .009) girls with obesity than in their normal-weight counterparts, without showing significant differences in boys. Nesfatin-1 showed a negative significant (P < .010) correlation with weight and BMI in girls but not in boys. A significant positive correlation of nesfatin-1 levels with insulin, HOMA, and leptin levels appears in girls after adjusting by age and BMI. A significant positive correlation (P = .003) was observed between nesfatin-1 and fat mass in older children. CONCLUSIONS Our study shows lower concentrations of nesfatin-1 related to obesity in girls but not in boys at two different ages. The existence of a sex-specific association between nesfatin-1 concentrations and presence of obesity highlights the need of an analysis by gender of the relationship of nesfatin-1 with obesity.
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Affiliation(s)
- Olaya de Dios
- Lipid Research Laboratory, IIS-Fundación Jiménez Díaz, Madrid, Spain
| | - Leticia Herrero
- Lipid Research Laboratory, IIS-Fundación Jiménez Díaz, Madrid, Spain
| | | | | | - Carmen Garcés
- Lipid Research Laboratory, IIS-Fundación Jiménez Díaz, Madrid, Spain
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26
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Zhang T, Wang M, Liu L, He B, Hu J, Wang Y. Hypothalamic nesfatin-1 mediates feeding behavior via MC3/4R-ERK signaling pathway after weight loss in obese Sprague-Dawley rats. Peptides 2019; 119:170080. [PMID: 31260713 DOI: 10.1016/j.peptides.2019.04.007] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2018] [Revised: 04/02/2019] [Accepted: 04/07/2019] [Indexed: 12/15/2022]
Abstract
Nesfatin-1 is an anorexic peptide derived from nucleobindin 2 (NUCB2). An increase in hypothalamic nesfatin-1 inhibits feeding behavior and promotes weight loss. However, the effects of weight loss on hypothalamic nesfatin-1 levels are unclear. In this study, obese rats lost weight in three ways: Calorie Restriction diet (CRD), Sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB). We found an increase in nesfatin-1 serum and cerebrospinal fluid levels after weight loss in obese Sprague-Dawley (SD) rats. Moreover, weight loss also increased hypothalamic melanocortin 3/4 receptor (MC3/4R) and extracellular regulated kinase phosphorylation (p-ERK) signaling. Third ventricle administration of antisense morpholino oligonucleotide (MON) against the gene encoding NUCB2 inhibited hypothalamic nesfatin-1 and p-ERK signaling, increased food intake and reduced body weight loss in SG and RYGB obese rats. Third ventricle administration of SHU9119 (MC3/4R blocker) blocked hypothalamic MC3/4R, inhibited p-ERK signaling, increased food intake and reduced body weight loss in SG and RYGB obese rats. These findings indicate that weight loss leads to an increase in hypothalamic nesfatin-1. The increase in hypothalamic nesfatin-1 participates in regulating feeding behavior through the MC3/4R-ERK signaling especially after SG and RYGB.
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Affiliation(s)
- Tianyi Zhang
- Fourth Affiliated Hospital of China Medical University, Chong Shan Road, Huanggu District, 110032, Shenyang, China.
| | - Mofei Wang
- Fourth Affiliated Hospital of China Medical University, Chong Shan Road, Huanggu District, 110032, Shenyang, China.
| | - Lei Liu
- Shengjing Hospital Affiliated to China Medical University, China.
| | - Bing He
- Shengjing Hospital Affiliated to China Medical University, China.
| | - Jingyao Hu
- Fourth Affiliated Hospital of China Medical University, Chong Shan Road, Huanggu District, 110032, Shenyang, China.
| | - Yong Wang
- Fourth Affiliated Hospital of China Medical University, Chong Shan Road, Huanggu District, 110032, Shenyang, China.
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27
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Idrizaj E, Garella R, Squecco R, Baccari MC. Adipocytes-released Peptides Involved in the Control of Gastrointestinal Motility. Curr Protein Pept Sci 2019; 20:614-629. [PMID: 30663565 DOI: 10.2174/1389203720666190121115356] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2018] [Revised: 01/07/2019] [Accepted: 01/09/2019] [Indexed: 12/18/2022]
Abstract
The present review focuses on adipocytes-released peptides known to be involved in the control of gastrointestinal motility, acting both centrally and peripherally. Thus, four peptides have been taken into account: leptin, adiponectin, nesfatin-1, and apelin. The discussion of the related physiological or pathophysiological roles, based on the most recent findings, is intended to underlie the close interactions among adipose tissue, central nervous system, and gastrointestinal tract. The better understanding of this complex network, as gastrointestinal motor responses represent peripheral signals involved in the regulation of food intake through the gut-brain axis, may also furnish a cue for the development of either novel therapeutic approaches in the treatment of obesity and eating disorders or potential diagnostic tools.
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Affiliation(s)
- Eglantina Idrizaj
- Department of Experimental and Clinical Medicine, Section of Physiological Sciences, University of Florence, Florence, Italy
| | - Rachele Garella
- Department of Experimental and Clinical Medicine, Section of Physiological Sciences, University of Florence, Florence, Italy
| | - Roberta Squecco
- Department of Experimental and Clinical Medicine, Section of Physiological Sciences, University of Florence, Florence, Italy
| | - Maria Caterina Baccari
- Department of Experimental and Clinical Medicine, Section of Physiological Sciences, University of Florence, Florence, Italy
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28
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Leung AKW, Ramesh N, Vogel C, Unniappan S. Nucleobindins and encoded peptides: From cell signaling to physiology. ADVANCES IN PROTEIN CHEMISTRY AND STRUCTURAL BIOLOGY 2019; 116:91-133. [PMID: 31036300 DOI: 10.1016/bs.apcsb.2019.02.001] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Nucleobindins (NUCBs) are DNA and calcium binding, secreted proteins with various signaling functions. Two NUCBs, nucleobindin-1 (NUCB1) and nucleobindin-2 (NUCB2), were discovered during the 1990s. These two peptides are shown to have diverse functions, including the regulation of inflammation and bone formation, among others. In 2006, Oh-I and colleagues discovered that three peptides encoded within the NUCB2 could be processed by prohormone convertases. These peptides were named nesfatin-1, 2 and 3, mainly due to the satiety and fat influencing properties of nesfatin-1. However, it was found that nesfatin-2 and -3 have no such effects. Nesfatin-1, especially its mid-segment, is very highly conserved across vertebrates. Although the receptor(s) that mediate nesfatin-1 effects are currently unknown, it is now considered an endogenous peptide with multiple functions, affecting central and peripheral tissues to regulate metabolism, reproduction, endocrine and other functions. We recently identified a nesfatin-1-like peptide (NLP) encoded within the NUCB1. Like nesfatin-1, NLP suppressed feed intake in mice and fish, and stimulated insulin secretion from pancreatic beta cells. There is considerable evidence available to indicate that nucleobindins and its encoded peptides are multifunctional regulators of cell biology and whole animal physiology. This review aims to briefly discuss the structure, distribution, functions and mechanism of action nucleobindins and encoded peptides.
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Affiliation(s)
- Adelaine Kwun-Wai Leung
- Department of Veterinary Biomedical Sciences, Western College of Veterinary Medicine, Saskatoon, SK, Canada
| | - Naresh Ramesh
- Department of Veterinary Biomedical Sciences, Western College of Veterinary Medicine, Saskatoon, SK, Canada
| | - Christine Vogel
- Department of Biology, New York University, New York, NY, United States
| | - Suraj Unniappan
- Department of Veterinary Biomedical Sciences, Western College of Veterinary Medicine, Saskatoon, SK, Canada.
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29
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Weibert E, Hofmann T, Stengel A. Role of nesfatin-1 in anxiety, depression and the response to stress. Psychoneuroendocrinology 2019; 100:58-66. [PMID: 30292960 DOI: 10.1016/j.psyneuen.2018.09.037] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2018] [Revised: 09/02/2018] [Accepted: 09/26/2018] [Indexed: 01/20/2023]
Abstract
Nesfatin-1 has been discovered a decade ago and since then drawn a lot of attention. The initially proposed anorexigenic effect was followed by the description of several other involvements such as a role in gastrointestinal motility, glucose homeostasis, cardiovascular functions and thermoregulation giving rise to a pleiotropic action of this peptide. The recent years witnessed mounting evidence on the involvement of nesfatin-1 in emotional processes as well. The present review will describe the peptide's relations to anxiety, depressiveness and stress in animal models and humans and also discuss existing gaps in knowledge in order to stimulate further research.
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Affiliation(s)
- Elena Weibert
- Charité Center for Internal Medicine and Dermatology, Department for Psychosomatic Medicine, Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany
| | - Tobias Hofmann
- Charité Center for Internal Medicine and Dermatology, Department for Psychosomatic Medicine, Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany
| | - Andreas Stengel
- Charité Center for Internal Medicine and Dermatology, Department for Psychosomatic Medicine, Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany; Department of Psychosomatic Medicine and Psychotherapy, Medical University Hospital Tübingen, Tübingen, Germany.
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30
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Saito R, Tanaka K, Nishimura H, Nishimura K, Sonoda S, Ueno H, Motojima Y, Yoshimura M, Maruyama T, Yamamoto Y, Kusuhara K, Ueta Y. Centrally administered kisspeptin suppresses feeding via nesfatin-1 and oxytocin in male rats. Peptides 2019; 112:114-124. [PMID: 30562556 DOI: 10.1016/j.peptides.2018.12.003] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2018] [Revised: 12/04/2018] [Accepted: 12/09/2018] [Indexed: 12/23/2022]
Abstract
Kisspeptin (KP), known as a hypothalamic neuropeptide, plays a critical role in the regulation of not only reproduction but also food intake. The anorectic neuropeptides, nesfatin-1 and oxytocin (OXT), are expressed in central nervous system, particulaly in various hypothalamic nuclei, and peripheral tissue. We examined the effects of the intracerebroventricular (icv) administration of KP-10 on feeding and nesfatin-1-immunoreactive (ir) or OXT-ir neurons in the rat hypothalamus, using Fos double immunohistochemistry in male rats. Cumulative food intake was remarkably decreased 0.5-3 h after icv administration of KP-10 (6.0 μg) compared to the vehicle treated and the KP-10 (3.8 μg) treated group. The icv administration of KP-10 significantly increased the number of nesfatin-1-ir neurons expressing Fos in the supraoptic nucleus (SON), paraventricular nucleus (PVN), arcuate nucleus (ARC), dorsal raphe nucleus, locus coeruleus, and nucleus tractus solitarius. The decreased food intake induced by KP-10 was significantly attenuated by pretreatment with the icv administration of antisense RNA against nucleobindin-2. After icv administration of KP-10, the percentages of OXT-ir neurons expressing FOS were remarkably higher in the SON and PVN than for vehicle treatment. The KP-10-induced anorexia was partially abolished by pretreatment with OXT receptor antagonist (OXTR-A). The percentage of nesfatin-1-ir neurons expressing Fos-ir in the ARC was also decreased by OXTR-A pretreatment. These results indicate that central administration of KP-10 activates nesfatin-1- and OXT neurons, and may play an important role in the suppression of feeding in male rats.
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Affiliation(s)
- Reiko Saito
- Department of Physiology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, 807-8555, Japan; Department of Pediatrics, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, 807-8555, Japan
| | - Kentaro Tanaka
- Department of Physiology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, 807-8555, Japan; Department of Pediatrics, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, 807-8555, Japan
| | - Haruki Nishimura
- Department of Physiology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, 807-8555, Japan
| | - Kazuaki Nishimura
- Department of Physiology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, 807-8555, Japan
| | - Satomi Sonoda
- Department of Physiology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, 807-8555, Japan
| | - Hiromichi Ueno
- Department of Physiology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, 807-8555, Japan
| | - Yasuhito Motojima
- Department of Physiology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, 807-8555, Japan
| | - Mitsuhiro Yoshimura
- Department of Physiology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, 807-8555, Japan
| | - Takashi Maruyama
- Department of Physiology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, 807-8555, Japan
| | - Yukiyo Yamamoto
- Department of Pediatrics, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, 807-8555, Japan
| | - Koichi Kusuhara
- Department of Pediatrics, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, 807-8555, Japan
| | - Yoichi Ueta
- Department of Physiology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, 807-8555, Japan.
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Psilopanagioti A, Nikou S, Papadaki H. Nucleobindin-2/Nesfatin-1 in the Human Hypothalamus Is Reduced in Obese Subjects and Colocalizes with Oxytocin, Vasopressin, Melanin-Concentrating Hormone, and Cocaine- and Amphetamine-Regulated Transcript. Neuroendocrinology 2019; 108:190-200. [PMID: 30625474 DOI: 10.1159/000496731] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2018] [Accepted: 01/09/2019] [Indexed: 11/19/2022]
Abstract
BACKGROUND/AIMS Nesfatin-1, processed from nucleobindin-2 (NUCB2), is a potent anorexigenic peptide being expressed in rodent hypothalamic nuclei and involved in the regulation of feeding behavior and body weight in animals. The present study aimed to investigate NUCB2/nesfatin-1 protein expression in the human hypothalamus as well as its correlation with body weight. METHODS Sections of hypothalamus and adjacent cholinergic basal forebrain nuclei, including the nucleus basalis of Meynert (NBM) and the diagonal band of Broca (DBB), from 25 autopsy cases (17 males, 8 females; 8 lean, 9 overweight, 8 obese) were examined using immunohistochemistry and double immunofluorescence labeling. RESULTS Prominent NUCB2/nesfatin-1 immunoexpression was detected in supraoptic, paraventricular, and infundibular nuclei, lateral hypothalamic area (LHA)/perifornical region, and NBM/DBB. NUCB2/nesfatin-1 was found to extensively colocalize with (a) oxytocin and vasopressin in paraventricular and supraoptic nuclei, (b) melanin-concentrating hormone in the LHA, and (c) cocaine- and amphetamine-regulated transcript in infundibular and paraventricular nuclei and LHA. Interestingly, in the LHA, NUCB2/nesfatin-1 protein expression was significantly decreased in obese, compared with lean (p < 0.01) and overweight (p < 0.05) subjects. CONCLUSIONS The findings of the present study are suggestive of a potential role for NUCB2/nesfatin-1 as an integral regulator of food intake and energy homeostasis in the human hypothalamus. In the LHA, an appetite- and reward-related brain area, reduced NUCB2/nesfatin-1 immunoexpression may contribute to dysregulation of homeostatic and/or hedonic feeding behavior and obesity. NUCB2/nesfatin-1 localization in NBM/DBB might imply its participation in the neuronal circuitry controlling cognitive influences on food intake and give impetus towards unraveling additional biological actions of NUCB2/nesfatin-1 in human neuronal networks.
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Affiliation(s)
- Aristea Psilopanagioti
- Department of Anatomy-Histology-Embryology, School of Medicine, University of Patras, Patras, Greece,
| | - Sofia Nikou
- Department of Anatomy-Histology-Embryology, School of Medicine, University of Patras, Patras, Greece
| | - Helen Papadaki
- Department of Anatomy-Histology-Embryology, School of Medicine, University of Patras, Patras, Greece
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Mirakhor Samani S, Ghasemi H, Rezaei Bookani K, Shokouhi B. SERUM NESFATIN-1 LEVEL IN HEALTHY SUBJECTS WITH WEIGHT-RELATED ABNORMALITIES AND NEWLY DIAGNOSED PATIENTS WITH TYPE 2 DIABETES MELLITUS; A CASE-CONTROL STUDY. ACTA ENDOCRINOLOGICA-BUCHAREST 2019; -5:69-73. [PMID: 31149062 DOI: 10.4183/aeb.2019.69] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Context Nesfatin-1 is a novel peptide with both central and peripheral anorexigenic regulatory properties. Besides its effects on food intake, few studies have suggested a possible role for this peptide in the pathogenesis of diabetes mellitus type 2. Objective To compare serum levels of nesfatin-1 between healthy, normal-weight persons and three groups including healthy underweight, healthy obese and diabetic subjects. Design Prospective, case-control study, performed between January 2015 and January 2016. Subjects and Methods Fasting levels in serum nesfatin-1 were measured in 30 healthy, normal-weight individuals (controls), 30 healthy underweight persons, 30 healthy obese persons, and 30 patients with newly diagnosed diabetes type 2 using standard enzyme-linked immunosorbent assay (ELISA) kits. Results The mean serum nesfatin-1 level was significantly higher in controls (2.61 ng/mL) compared to that in obese (1.13 ng/mL) and diabetic (0.99 ng/mL) patients; and significantly lower than that in the underweight group (3.50 ng/mL). The obese and diabetic groups were comparable in this regard. No significant association was found between serum nesfatin-1 level and age, sex, or body mass index. Conclusions Serum nesfatin-1 is possibly associated with weight-related abnormalities in otherwise healthy subjects and diabetes type 2. Obesity and diabetes type 2 may share a common pathologic point in this regard.
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Affiliation(s)
- S Mirakhor Samani
- Qazvin University of Medical Sciences, Department of Pathology, Qazvin, Tabriz University of Medical Sciences, Tabriz, Iran
| | - H Ghasemi
- Department of Internal Medicine, Tabriz, Iran
| | | | - B Shokouhi
- Urmia University of Medical Sciences, Department of Internal Medicine, Urmia, Iran
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Bertucci JI, Blanco AM, Sánchez‐Bretaño A, Unniappan S, Canosa LF. Ghrelin and NUCB2/Nesfatin‐1 Co‐Localization With Digestive Enzymes in the Intestine of Pejerrey (
Odontesthes bonariensis
). Anat Rec (Hoboken) 2018; 302:973-982. [DOI: 10.1002/ar.24012] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2017] [Revised: 07/30/2018] [Accepted: 09/11/2018] [Indexed: 12/13/2022]
Affiliation(s)
- Juan Ignacio Bertucci
- Instituto Tecnológico de Chascomús (INTECH), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)‐Universidad Nacional de San Martín (UNSAM) Buenos Aires Argentina
- Laboratory of Integrative Neuroendocrinology, Department of Veterinary Biomedical SciencesWestern College of Veterinary Medicine, University of Saskatchewan Saskatoon Saskatchewan Canada
| | - Ayelén Melisa Blanco
- Laboratory of Integrative Neuroendocrinology, Department of Veterinary Biomedical SciencesWestern College of Veterinary Medicine, University of Saskatchewan Saskatoon Saskatchewan Canada
- Departamento de Fisiología (Fisiología Animal II), Facultad de BiologíaUniversidad Complutense de Madrid Madrid Spain
| | - Aida Sánchez‐Bretaño
- Department of Pharmacology and Toxicology, and Neuroscience InstituteMorehouse School of Medicine 720 Westview Drive, GA, 30310 Atlanta Georgia
| | - Suraj Unniappan
- Laboratory of Integrative Neuroendocrinology, Department of Veterinary Biomedical SciencesWestern College of Veterinary Medicine, University of Saskatchewan Saskatoon Saskatchewan Canada
| | - Luis Fabián Canosa
- Instituto Tecnológico de Chascomús (INTECH), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)‐Universidad Nacional de San Martín (UNSAM) Buenos Aires Argentina
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Zhang X, Qi J, Tang N, Wang S, Wu Y, Chen H, Tian Z, Wang B, Chen D, Li Z. Intraperitoneal injection of nesfatin-1 primarily through the CCK-CCK1R signal pathway affects expression of appetite factors to inhibit the food intake of Siberian sturgeon (Acipenser baerii). Peptides 2018; 109:14-22. [PMID: 30261207 DOI: 10.1016/j.peptides.2018.09.008] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2018] [Revised: 09/20/2018] [Accepted: 09/21/2018] [Indexed: 12/13/2022]
Abstract
Nesfatin-1 is an 82-amino acid protein derived from nucleobindin 2 (NUCB2), which could inhibit food intake in fish and mammals. However, the neuroendocrine mechanism of nesfatin-1 in animal appetite regulation is unclear. To explore the feeding mechanism of nesfatin-1 in Siberian sturgeon (Acipenser baerii), intraperitoneal injections of nesfatin-1 and sulfated cholecystokinin octapeptide (CCK8), Lorglumide (CCK1R selective antagonist), or LY 225,910 (CCK2R selective antagonist) were performed. Co-injection of nesfatin-1 and CCK8 synergistically significantly decreased the food intake in 1 h. Lorglumide reversed the anorectic effect of nesfatin-1, but LY 225,910 had no effect. Moreover, Lorglumide could also reverse the expressions of appetite factors including nucb2, cck, unc3, cart, apelin, pyy, and npy induced by nesfatin-1 in the brain, stomach, and liver, while LY 225,910 partially reversed these changes. These results indicate that nesfatin-1 inhibits the appetite of Siberian sturgeon mainly through the CCK-CCK1R signaling pathway.
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Affiliation(s)
- Xin Zhang
- Department of Aquaculture, College of Animal Science and Technology, Sichuan Agricultural University, 211# Huimin Road, Chengdu, Sichuan, China; The Key Laboratory of Mariculture, Ministry of Education, Fisheries College, Ocean University of China, 5# Yushan Road, Qingdao, Shandong, China
| | - Jinwen Qi
- Department of Aquaculture, College of Animal Science and Technology, Sichuan Agricultural University, 211# Huimin Road, Chengdu, Sichuan, China
| | - Ni Tang
- Department of Aquaculture, College of Animal Science and Technology, Sichuan Agricultural University, 211# Huimin Road, Chengdu, Sichuan, China
| | - Shuyao Wang
- Department of Aquaculture, College of Animal Science and Technology, Sichuan Agricultural University, 211# Huimin Road, Chengdu, Sichuan, China
| | - Yuanbing Wu
- Department of Aquaculture, College of Animal Science and Technology, Sichuan Agricultural University, 211# Huimin Road, Chengdu, Sichuan, China
| | - Hu Chen
- Department of Aquaculture, College of Animal Science and Technology, Sichuan Agricultural University, 211# Huimin Road, Chengdu, Sichuan, China
| | - Zhengzhi Tian
- Department of Aquaculture, College of Animal Science and Technology, Sichuan Agricultural University, 211# Huimin Road, Chengdu, Sichuan, China
| | - Bin Wang
- Department of Aquaculture, College of Animal Science and Technology, Sichuan Agricultural University, 211# Huimin Road, Chengdu, Sichuan, China
| | - Defang Chen
- Department of Aquaculture, College of Animal Science and Technology, Sichuan Agricultural University, 211# Huimin Road, Chengdu, Sichuan, China
| | - Zhiqiong Li
- Department of Aquaculture, College of Animal Science and Technology, Sichuan Agricultural University, 211# Huimin Road, Chengdu, Sichuan, China.
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Schalla MA, Stengel A. Current Understanding of the Role of Nesfatin-1. J Endocr Soc 2018; 2:1188-1206. [PMID: 30302423 PMCID: PMC6169466 DOI: 10.1210/js.2018-00246] [Citation(s) in RCA: 75] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2018] [Accepted: 09/05/2018] [Indexed: 12/13/2022] Open
Abstract
Nesfatin-1 was discovered in 2006 and implicated in the regulation of food intake. Subsequently, its widespread central and peripheral distribution gave rise to additional effects. Indeed, a multitude of actions were described, including modulation of gastrointestinal functions, glucose and lipid metabolism, thermogenesis, mediation of anxiety and depression, as well as cardiovascular and reproductive functions. Recent years have witnessed a great increase in our knowledge of these effects and their underlying mechanisms, which will be discussed in the present review. Lastly, gaps in knowledge will be highlighted to foster further studies.
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Affiliation(s)
- Martha A Schalla
- Charité Center for Internal Medicine and Dermatology, Department for Psychosomatic Medicine, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin
| | - Andreas Stengel
- Charité Center for Internal Medicine and Dermatology, Department for Psychosomatic Medicine, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin
- Department of Psychosomatic Medicine and Psychotherapy, Medical University Hospital Tübingen, 72076 Tübingen, Germany
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Korucu CÇ, Atay İM, Zayıf SS, Gültekin F. May nesfatin-1 be a state marker in major depressive disorder with suicidal ideation? Psychiatry Res 2018; 267:272-276. [PMID: 29940459 DOI: 10.1016/j.psychres.2018.05.086] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2017] [Revised: 05/05/2018] [Accepted: 05/29/2018] [Indexed: 12/17/2022]
Abstract
The best known effects of nesfatin-1 are on appetite and metabolic regulation. Moreover, several research suggest that nesfatin-1 play a role in stress responses. This molecule may be involved in the pathophysiology of mood disorders and suicidal behavior. We compared nesfatin-1 levels between depressed patients with suicidal ideation (n = 32, mean ± SD, 1,40 ± 0.11), without suicidal ideation(n = 31, 1.46 ± 0.14) and healthy controls (n = 32, 1.52 ± 0.13). Suicidal ideation was assessed with the Suicide Probability Scale, Scale for Suicide Ideation and depressive symptoms were evaluated with the Hamilton Depression Rating Scale. Blood samples were collected to measure serum nesfatin-1levels by using ELISA method. The study revealed that serum nesfatin-1 levels were significantly lower in MDD with suicidal ideation than in healthy volunteers (p < 0.001). There were a negative correlation between the scores of suicidal ideation and nesfatin-1 levels in MDD with SI group (r = -0.215; p = 0.016). In the future, nesfatin-1 levels may one day be applied in predicting and monitoring patients' suicide risk. Further prospective studies are required to elucidate this potential association.
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Affiliation(s)
- Cafer Çağrı Korucu
- Department of Psychiatry, Usak University Education and Research Hospital, Usak, Turkey.
| | - İnci Meltem Atay
- Department of Psychiatry, Faculty of Medicine, Suleyman Demirel University, Isparta, Turkey
| | - Seden Sert Zayıf
- Department of Biochemistry, Faculty of Medicine, Suleyman Demirel University, Isparta, Turkey
| | - Fatih Gültekin
- Department of Biochemistry, Faculty of Medicine, Suleyman Demirel University, Isparta, Turkey
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Zhang X, Wang S, Chen H, Tang N, Qi J, Wu Y, Hao J, Tian Z, Wang B, Chen D, Li Z. The inhibitory effect of NUCB2/nesfatin-1 on appetite regulation of Siberian sturgeon (Acipenser baerii Brandt). Horm Behav 2018; 103:111-120. [PMID: 29940158 DOI: 10.1016/j.yhbeh.2018.06.008] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2018] [Revised: 06/18/2018] [Accepted: 06/20/2018] [Indexed: 12/19/2022]
Abstract
Since NUCB2 was discovered, the information about NUCB2/nesfatin-1 in appetite regulation in both mammals and teleost has been still limited. The present study aims to determine the effects of nesfatin-1 on food intake and to explore the appetite mechanism in Siberian sturgeon. In this study, nucb2 cDNA sequence of 1571 bp was obtained, and the mRNA expression of nucb2 was abundant in brain and liver. Levels of nucb2 were appreciably increased in brain after feeding 1 and 3 h, while significantly decreased within fasting 15 days. Except for fasting 1 day, the expression pattern of nucb2 in the liver was similar to the brain. Acute intraperitoneal (i.p.) injection of nesfatin-1 inhibited the food intake during 0-1 h in a dose-dependent manner and 50 or 100 ng/g BW nesfatin-1 significantly decreased the cumulative food intake during 3 h. The daily food intake and cumulative food intake were remarkably reduced post chronic (7 days) i.p. injection. Moreover, chronic i.p. injection of nesfatin-1 affected the expression of appetite factors including cart, apelin and pyy in the brain, stomach and liver with the consistent pattern of change, while the levels of cck, ucn3 and nucb2 in these have different patterns. This study demonstrates that nesfatin-1 acts as a satiety factor in reducing the short-term and long-term food intake of Siberian sturgeon. Therefore, the data suggesting nesfatin-1 inhibits the appetite through different signal pathways in the central and peripheral endocrine systems of Siberian sturgeon.
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Affiliation(s)
- Xin Zhang
- Department of Aquaculture, College of Animal Science and Technology, Sichuan Agricultural University, 211# Huimin Road, Chengdu, Sichuan, China; The Key Laboratory of Mariculture, Ministry of Education, Fisheries College, Ocean University of China, 5# Yushan Road, Qingdao, Shandong, China
| | - Shuyao Wang
- Department of Aquaculture, College of Animal Science and Technology, Sichuan Agricultural University, 211# Huimin Road, Chengdu, Sichuan, China
| | - Hu Chen
- Department of Aquaculture, College of Animal Science and Technology, Sichuan Agricultural University, 211# Huimin Road, Chengdu, Sichuan, China
| | - Ni Tang
- Department of Aquaculture, College of Animal Science and Technology, Sichuan Agricultural University, 211# Huimin Road, Chengdu, Sichuan, China
| | - Jinwen Qi
- Department of Aquaculture, College of Animal Science and Technology, Sichuan Agricultural University, 211# Huimin Road, Chengdu, Sichuan, China
| | - Yuanbing Wu
- Department of Aquaculture, College of Animal Science and Technology, Sichuan Agricultural University, 211# Huimin Road, Chengdu, Sichuan, China
| | - Jin Hao
- Department of Aquaculture, College of Animal Science and Technology, Sichuan Agricultural University, 211# Huimin Road, Chengdu, Sichuan, China
| | - Zhengzhi Tian
- Department of Aquaculture, College of Animal Science and Technology, Sichuan Agricultural University, 211# Huimin Road, Chengdu, Sichuan, China
| | - Bin Wang
- Department of Aquaculture, College of Animal Science and Technology, Sichuan Agricultural University, 211# Huimin Road, Chengdu, Sichuan, China
| | - Defang Chen
- Department of Aquaculture, College of Animal Science and Technology, Sichuan Agricultural University, 211# Huimin Road, Chengdu, Sichuan, China
| | - Zhiqiong Li
- Department of Aquaculture, College of Animal Science and Technology, Sichuan Agricultural University, 211# Huimin Road, Chengdu, Sichuan, China.
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Bülbül M, Travagli RA. Novel transmitters in brain stem vagal neurocircuitry: new players on the pitch. Am J Physiol Gastrointest Liver Physiol 2018; 315:G20-G26. [PMID: 29597355 PMCID: PMC6109706 DOI: 10.1152/ajpgi.00059.2018] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
The last few decades have seen a major increase in the number of neurotransmitters and neuropeptides recognized as playing a role in brain stem neurocircuits, including those involved in homeostatic functions such as stress responsiveness, gastrointestinal motility, feeding, and/or arousal/wakefulness. This minireview will focus on the known physiological role of three of these novel neuropeptides, i.e., apelin, nesfatin-1, and neuropeptide-S, with a special emphasis on their hypothetical roles in vagal signaling related to gastrointestinal motor functions.
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Affiliation(s)
- Mehmet Bülbül
- 1Faculty of Medicine, Department of Physiology, Akdeniz UniversityAntalya, Turkey
| | - R. Alberto Travagli
- 2Department of Neural and Behavioral Neurosciences, Pennsylvania State University College of Medicine, Hershey, Pennsylvania
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Pałasz A, Janas-Kozik M, Borrow A, Arias-Carrión O, Worthington JJ. The potential role of the novel hypothalamic neuropeptides nesfatin-1, phoenixin, spexin and kisspeptin in the pathogenesis of anxiety and anorexia nervosa. Neurochem Int 2018; 113:120-136. [DOI: 10.1016/j.neuint.2017.12.006] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2017] [Revised: 12/13/2017] [Accepted: 12/14/2017] [Indexed: 02/07/2023]
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Blanco AM, Velasco C, Bertucci JI, Soengas JL, Unniappan S. Nesfatin-1 Regulates Feeding, Glucosensing and Lipid Metabolism in Rainbow Trout. Front Endocrinol (Lausanne) 2018; 9:484. [PMID: 30210451 PMCID: PMC6121026 DOI: 10.3389/fendo.2018.00484] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2018] [Accepted: 08/06/2018] [Indexed: 12/21/2022] Open
Abstract
Nesfatin-1 is an 82 amino acid peptide that has been involved in a wide variety of physiological functions in both mammals and fish. This study aimed to elucidate the role of nesfatin-1 on rainbow trout food intake, and its putative effects on glucose and fatty acid sensing systems. Intracerebroventricular administration of 25 ng/g nesfatin-1 resulted in a significant inhibition of appetite, likely mediated by the activation of central POMC and CART. Nesfatin-1 stimulated the glucosensing machinery (changes in sglt1, g6pase, gsase, and gnat3 mRNA expression) in the hindbrain and hypothalamus. Central fatty acid sensing mechanisms were unaltered by nesfatin-1, but this peptide altered the expression of mRNAs encoding factors regulating lipid metabolism (fat/cd36, acly, mcd, fas, lpl, pparα, and pparγ), suggesting that nesfatin-1 promotes lipid accumulation in neurons. In the liver, intracerebroventricular nesfatin-1 treatment resulted in decreased capacity for glucose use and lipogenesis, and increased the potential of fatty acid oxidation. Altogether, the present results demonstrate that nesfatin-1 is involved in the homeostatic regulation of food intake and metabolism in fish.
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Affiliation(s)
- Ayelén M. Blanco
- Laboratory of Integrative Neuroendocrinology, Department of Veterinary Biomedical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK, Canada
- Laboratorio de Fisioloxía Animal, Departamento de Bioloxía Funcional e Ciencias da Saúde, Facultade de Bioloxía and Centro de Investigación Mariña, Universidade de Vigo, Vigo, Spain
| | - Cristina Velasco
- Laboratory of Integrative Neuroendocrinology, Department of Veterinary Biomedical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK, Canada
- Laboratorio de Fisioloxía Animal, Departamento de Bioloxía Funcional e Ciencias da Saúde, Facultade de Bioloxía and Centro de Investigación Mariña, Universidade de Vigo, Vigo, Spain
| | - Juan I. Bertucci
- Laboratory of Integrative Neuroendocrinology, Department of Veterinary Biomedical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK, Canada
- Instituto de Investigaciones Biotecnológicas-Instituto Tecnológico Chascomús, Chascomús, Argentina
| | - José L. Soengas
- Laboratorio de Fisioloxía Animal, Departamento de Bioloxía Funcional e Ciencias da Saúde, Facultade de Bioloxía and Centro de Investigación Mariña, Universidade de Vigo, Vigo, Spain
| | - Suraj Unniappan
- Laboratory of Integrative Neuroendocrinology, Department of Veterinary Biomedical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK, Canada
- *Correspondence: Suraj Unniappan
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The effect of Nesfatin-1 on food intake in neonatal chicks: role of CRF1 /CRF2 and H1/ H3 receptors. Vet Res Commun 2017; 42:39-47. [DOI: 10.1007/s11259-017-9706-9] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2017] [Accepted: 12/19/2017] [Indexed: 01/28/2023]
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Prinz P, Scharner S, Friedrich T, Schalla M, Goebel-Stengel M, Rose M, Stengel A. Central and peripheral expression sites of phoenixin-14 immunoreactivity in rats. Biochem Biophys Res Commun 2017; 493:195-201. [DOI: 10.1016/j.bbrc.2017.09.048] [Citation(s) in RCA: 35] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2017] [Accepted: 09/10/2017] [Indexed: 12/13/2022]
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Akiyama Y, Yoshimura M, Nishimura K, Nishimura H, Sonoda S, Ueno H, Mitojima Y, Saito R, Maruyama T, Nonaka Y, Hashimoto H, Uezono Y, Hirata K, Ueta Y. Activation of central nesfatin-1/NucB2 after intraperitoneally administered cisplatin in rats. Biochem Biophys Res Commun 2017. [DOI: 10.1016/j.bbrc.2017.06.119] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
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Saito R, Sonoda S, Ueno H, Motojima Y, Yoshimura M, Maruyama T, Hashimoto H, Tanaka K, Yamamoto Y, Kusuhara K, Ueta Y. Involvement of central nesfatin-1 neurons on oxytocin-induced feeding suppression in rats. Neurosci Lett 2017; 655:54-60. [PMID: 28684238 DOI: 10.1016/j.neulet.2017.06.049] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2017] [Revised: 06/25/2017] [Accepted: 06/27/2017] [Indexed: 11/26/2022]
Abstract
Peripheral anorectic hormones, such as peptide YY (PYY) and oxytocin (OXT), suppress food intake. A newly identified anorectic neuropeptide, nesfatin-1, is synthesized in both peripheral tissue and the central nervous system, particularly by various nuclei in the hypothalamus and brainstem. Here, we examined the effects of intraperitoneal (ip) administration of PYY3-36, OXT, and OXT analog, on nesfatin-1-immunoreactive (ir) neurons in the rat hypothalamus and brainstem, using Fos double fluorescence-immunohistochemistry. The ip administration of OXT and OXT analog significantly increased the number of nesfatin-1-ir neurons expressing Fos-ir in the paraventricular nucleus, the arcuate nucleus, and the nucleus tractus solitarius, but not in the supraoptic nucleus, the lateral hypothalamic area, and the area postrema. No differences in the percentage of nesfatin-1-ir neurons expressing Fos in the nuclei of the hypothalamus and brainstem were observed, between rats treated with vehicle or those treated with PYY3-36. The decreased food intake, induced by OXT and OXT analog, was attenuated significantly by pretreatment with intracerebroventricular administration of antisense nesfatin-1. These results suggested that nesfatin-1-expressing neurons in the hypothalamus and brainstem may play a role in sensing the peripheral level of OXT and its suppression of feeding in rats.
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Affiliation(s)
- Reiko Saito
- Department of Physiology, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, Fukuoka, 807-8555, Japan; Department of Pediatrics, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Fukuoka 807-8555, Japan
| | - Satomi Sonoda
- Department of Physiology, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, Fukuoka, 807-8555, Japan
| | - Hiromichi Ueno
- Department of Physiology, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, Fukuoka, 807-8555, Japan
| | - Yasuhito Motojima
- Department of Physiology, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, Fukuoka, 807-8555, Japan
| | - Mitsuhiro Yoshimura
- Department of Physiology, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, Fukuoka, 807-8555, Japan
| | - Takashi Maruyama
- Department of Physiology, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, Fukuoka, 807-8555, Japan
| | - Hirofumi Hashimoto
- Department of Physiology, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, Fukuoka, 807-8555, Japan
| | - Kentaro Tanaka
- Department of Physiology, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, Fukuoka, 807-8555, Japan; Department of Pediatrics, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Fukuoka 807-8555, Japan
| | - Yukiyo Yamamoto
- Department of Pediatrics, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Fukuoka 807-8555, Japan
| | - Koichi Kusuhara
- Department of Pediatrics, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Fukuoka 807-8555, Japan
| | - Yoichi Ueta
- Department of Physiology, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, Fukuoka, 807-8555, Japan.
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Hofmann T, Weibert E, Ahnis A, Obbarius A, Elbelt U, Rose M, Klapp BF, Stengel A. Alterations of circulating NUCB2/nesfatin-1 during short term therapeutic improvement of anxiety in obese inpatients. Psychoneuroendocrinology 2017; 79:107-115. [PMID: 28273586 DOI: 10.1016/j.psyneuen.2017.02.021] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2017] [Accepted: 02/17/2017] [Indexed: 12/18/2022]
Abstract
In addition to its anorexigenic properties in the neuroendocrine regulation of hunger and satiety, mounting evidence indicates a role for NUCB2/nesfatin-1 in the regulation of emotional stress responses which seems to occur in a sex-specific way. In the present study, we investigated the association of NUCB2/nesfatin-1 plasma levels with anxiety, depressiveness and perceived stress in obese men and women and their alterations during inpatient treatment. We expected a decrease of NUCB2/nesfatin-1 levels in female and an increase in male patients reporting a relevant alleviation of anxiety. We analyzed 69 inpatients (44 female, 25 male; body mass index, mean: 50.2±9.5kg/m2, range: 31.8-76.5kg/m2; mean age: 45.0±12.4years) hospitalized due to morbid obesity with mental (not necessarily anxiety disorders) and somatic comorbidities. NUCB2/nesfatin-1 plasma levels were measured by ELISA. Anxiety (GAD-7), depressiveness (PHQ-9) and perceived stress (PSQ-20) were concurrently determined as patient-reported outcomes. All measurements were carried out at the initiation of and during inpatient treatment when a clinically meaningful improvement of anxiety was achieved (≥5 points on GAD-7) or missed (±1 point). NUCB2/nesfatin-1 was positively correlated with anxiety scores in women at the beginning of (r=0.411; p=0.006) and during (r=0.301; p=0.047) inpatient treatment. In men, a significant negative correlation was observed following treatment (r=-0.469; p=0.018), while at the outset of treatment only a trend was observed (r=-0.381; p=0.059). Unexpectedly, neither women (n=19; at beginning vs. during treatment; 0.49±1.00ng/ml vs. 0.38±0.72ng/ml; p=0.687) nor men (n=9; 0.17±0.31ng/ml vs. 0.19±0.36ng/ml; p=0.427) who improved in anxiety scores (p<0.001) displayed significant changes of NUCB2/nesfatin-1 plasma levels, although the direction of change was as expected with a decrease in women (-23.3%) and an increase in men (+12.4%). In addition, the change of NUCB2/nesfatin-1 was not explained by the course of anxiety (women: p=0.587; men: p=0.373). In conclusion, women and men showed an inverse association between NUCB2/nesfatin-1 and anxiety with a positive correlation in women and a negative correlation in men (although this correlation was not statistically significant in men at the beginning of treatment). However, no significant change of NUCB2/nesfatin-1 following improvement of anxiety has been observed. This might be due to the short observation interval, or due to too small anxiety improvements associated with too low baseline anxiety levels.
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Affiliation(s)
- Tobias Hofmann
- Charité Center for Internal Medicine and Dermatology, Department of Psychosomatic Medicine, Charité - Universitätsmedizin Berlin, Berlin, Germany.
| | - Elena Weibert
- Charité Center for Internal Medicine and Dermatology, Department of Psychosomatic Medicine, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Anne Ahnis
- Charité Center for Internal Medicine and Dermatology, Department of Psychosomatic Medicine, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Alexander Obbarius
- Charité Center for Internal Medicine and Dermatology, Department of Psychosomatic Medicine, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Ulf Elbelt
- Charité Center for Internal Medicine and Dermatology, Department of Psychosomatic Medicine, Charité - Universitätsmedizin Berlin, Berlin, Germany; Charité Center for Internal Medicine with Gastroenterology and Nephrology, Division for Endocrinology, Diabetes and Nutrition, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Matthias Rose
- Charité Center for Internal Medicine and Dermatology, Department of Psychosomatic Medicine, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Burghard F Klapp
- Charité Center for Internal Medicine and Dermatology, Department of Psychosomatic Medicine, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Andreas Stengel
- Charité Center for Internal Medicine and Dermatology, Department of Psychosomatic Medicine, Charité - Universitätsmedizin Berlin, Berlin, Germany
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Yang GT, Zhao HY, Kong Y, Sun NN, Dong AQ. Study of the effects of nesfatin-1 on gastric function in obese rats. World J Gastroenterol 2017; 23:2940-2947. [PMID: 28522911 PMCID: PMC5413788 DOI: 10.3748/wjg.v23.i16.2940] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2016] [Revised: 02/15/2017] [Accepted: 03/02/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the effects of nesfatin-1 on gastric function in obese rats.
METHODS The obese rat model was induced by a high-fat diet. The gastric emptying rate and gastric acid secretory capacity of the rats were determined after treatment with different drug concentrations of nesfatin-1 and administration routes. Based on this, the expression of H+/K+-ATPase was measured using RT-PCR and western blot to preliminarily explore the mechanism of gastric acid secretion changes.
RESULTS Body weight, body length, and Lee’s index of the rats significantly increased in the high-fat diet-induced obese rat model. Two hours after lateral intracerebroventricular injection of nesfatin-1, the gastric emptying rate and gastric acid secretory capacity of rats decreased. Four hours after injection, both were restored to normal levels. In addition, the expression of H+/K+-ATPase decreased and moved in line with changes in gastric acid secretory capacity. This in vivo experiment revealed that intracerebroventricular injection of nesfatin-1, rather than intravenous injection, could suppress gastric function in obese rats. Moreover, its effect on the gastric emptying and gastric acid secretory capacity of rats is dose-dependent within a certain period of time.
CONCLUSION Through this research, we provide a theoretical basis for further studies on nesfatin-1, a potential anti-obesity drug.
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Xu L, Wang H, Gong Y, Pang M, Sun X, Guo F, Gao S. Nesfatin-1 regulates the lateral hypothalamic area melanin-concentrating hormone-responsive gastric distension-sensitive neurons and gastric function via arcuate nucleus innervation. Metabolism 2017; 67:14-25. [PMID: 28081774 DOI: 10.1016/j.metabol.2016.10.010] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2016] [Revised: 10/18/2016] [Accepted: 10/23/2016] [Indexed: 12/15/2022]
Abstract
Nesfatin-1, a recently discovered neuropeptide involved in satiety. Recent studies have revealed that central nesfatin-1 inhibits gastric emptying and gastric acid secretion, though the mechanisms involved in these processes are not known. We aim to explore the effects of nesfatin-1 on a population of gastric distension (GD)-sensitive neurons in the lateral hypothalamus (LHA), gastric motility, and gastric secretion and the role for an arcuate nucleus (Arc)-LHA neural pathway in these processes. Single unit extracellular discharge recordings were made in of LHA. Further, gastric motility and gastric secretion in rats were monitored. Retrograde tracing and fluorescent immunohistochemical staining were used to explore nesfatin-1 neuron projection. The results revealed that administration of nesfatin-1 to the LHA or electric stimulation of the Arc could alter the neuronal activity of melanin-concentrating hormone (MCH)-responsive, GD-responsive neurons in LHA, which could be blocked by pretreatment with MCH receptor-1 antagonist PMC-3881-PI or weakened by pretreatment of a nesfatin-1 antibody in LHA. Administration of nesfatin-1 into LHA could inhibit gastric motility and gastric secretion, and these effects could be enhanced by administration of PMC-3881-PI. Electrical stimulation of Arc promoted the gastric motility and gastric secretion. Nesfatin-1 antibody or PMC-3881-PI pretreatment to LHA had no effect on Arc stimulation-induced gastric motility, but these pretreatments did alter Arc stimulation-induced effects on gastric secretion. Our findings suggest that nesfatin-1 signaling in LHA participates in the regulation of efferent information from the gastrointestinal tract and gastric secretion which also involve MCH signaling. Further, they show that a nesfatin-1-positive Arc to LHA pathway is critical for these effects.
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Affiliation(s)
- Luo Xu
- Department of Pathophysiology, Medical College of Qingdao University, Qingdao, Shandong, China.
| | - Hongbo Wang
- Department of Gastroenterology, Jimo People's Hospital, Qingdao, Shandong, China
| | - Yanling Gong
- Department of Pharmacy, College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao, Shandong, China
| | - Mingjie Pang
- Department of Otolaryngology, Qingdao Municipal Hospital (Group), Qingdao, Shandong, China
| | - Xiangrong Sun
- Department of Pathophysiology, Medical College of Qingdao University, Qingdao, Shandong, China
| | - Feifei Guo
- Department of Pathophysiology, Medical College of Qingdao University, Qingdao, Shandong, China
| | - Shengli Gao
- Department of Pathophysiology, Medical College of Qingdao University, Qingdao, Shandong, China
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Goebel-Stengel M, Stengel A. Role of Brain NUCB2/nesfatin-1 in the Stress-induced Modulation of Gastrointestinal Functions. Curr Neuropharmacol 2017; 14:882-891. [PMID: 27281021 PMCID: PMC5333592 DOI: 10.2174/1570159x14666160601153202] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2016] [Revised: 02/26/2016] [Accepted: 05/31/2016] [Indexed: 02/07/2023] Open
Abstract
Background Nucleobindin2 (NUCB2)/nesfatin-1 plays a well-established role in homeostatic functions associated with food intake and stress integration. Aim This review focusses on NUCB2/nesfatin-1’s central effects on gastrointestinal functions and will summarize the effects on food intake, motility and secretion with focus on the upper gastrointestinal tract. Results We will highlight the stressors that influence brain NUCB2/nesfatin-1 expression and discuss functional implications. In addition to traditional acute psychological and physical stressors such as restraint stress and abdominal surgery we will look at immunological, visceral and metabolic stressors as well as a chronic combination stress model that have been shown to affect NUCB2/nesfatin-1 signaling and describe associated functional consequences.
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Affiliation(s)
| | - Andreas Stengel
- First Internal Medicine and Dermatology, Department of Psychosomatic Medicine, Hindenburgdamm 30, 12200 Berlin, Germany
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Dore R, Levata L, Lehnert H, Schulz C. Nesfatin-1: functions and physiology of a novel regulatory peptide. J Endocrinol 2017; 232:R45-R65. [PMID: 27754932 DOI: 10.1530/joe-16-0361] [Citation(s) in RCA: 90] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2016] [Accepted: 10/17/2016] [Indexed: 12/12/2022]
Abstract
Nesfatin-1 was identified in 2006 as a potent anorexigenic peptide involved in the regulation of homeostatic feeding. It is processed from the precursor-peptide NEFA/nucleobindin 2 (NUCB2), which is expressed both in the central nervous system as well as in the periphery, from where it can access the brain via non-saturable transmembrane diffusion. In hypothalamus and brainstem, nesfatin-1 recruits the oxytocin, the melancortin and other systems to relay its anorexigenic properties. NUCB2/nesfatin-1 peptide expression in reward-related areas suggests that nesfatin-1 might also be involved in hedonic feeding. Besides its initially discovered anorexigenic properties, over the last years, other important functions of nesfatin-1 have been discovered, many of them related to energy homeostasis, e.g. energy expenditure and glucose homeostasis. Nesfatin-1 is not only affecting these physiological processes but also the alterations of the metabolic state (e.g. fat mass, glycemic state) have an impact on the synthesis and release of NUCB2 and/or nesfatin-1. Furthermore, nesfatin-1 exerts pleiotropic actions at the level of cardiovascular and digestive systems, as well as plays a role in stress response, behavior, sleep and reproduction. Despite the recent advances in nesfatin-1 research, a putative receptor has not been identified and furthermore potentially distinct functions of nesfatin-1 and its precursor NUCB2 have not been dissected yet. To tackle these open questions will be the major objectives of future research to broaden our knowledge on NUCB2/nesfatin-1.
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Affiliation(s)
- Riccardo Dore
- Department of Internal Medicine ICenter of Brain, Behavior and Metabolism (CBBM), University of Lübeck, Lübeck, Germany
| | - Luka Levata
- Department of Internal Medicine ICenter of Brain, Behavior and Metabolism (CBBM), University of Lübeck, Lübeck, Germany
| | - Hendrik Lehnert
- Department of Internal Medicine ICenter of Brain, Behavior and Metabolism (CBBM), University of Lübeck, Lübeck, Germany
| | - Carla Schulz
- Department of Internal Medicine ICenter of Brain, Behavior and Metabolism (CBBM), University of Lübeck, Lübeck, Germany
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Feng H, Wang Q, Guo F, Han X, Pang M, Sun X, Gong Y, Xu L. Nesfatin-1 influences the excitability of gastric distension-responsive neurons in the ventromedial hypothalamic nucleus of rats. Physiol Res 2016; 66:335-344. [PMID: 27982684 DOI: 10.33549/physiolres.933347] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
The present study investigated the effects of nesfatin-1 on gastric distension (GD)-responsive neurons via an interaction with corticotropin-releasing factor (CRF) receptor signaling in the ventromedial hypothalamic nucleus (VMH), and the potential regulation of these effects by hippocampal projections to VMH. Extracellular single-unit discharges were recorded in VHM following administration of nesfatin-1. The projection of nerve fibers and expression of nesfatin-1 were assessed by retrograde tracing and fluoro-immunohistochemical staining, respectively. Results showed that there were GD-responsive neurons in VMH; Nesfatin-1 administration and electrical stimulation of hippocampal CA1 sub-region altered the firing rate of these neurons. These changes could be partially blocked by pretreatment with the non-selective CRF antagonist astressin-B or an antibody to NUCB2/nesfatin-1. Electrolytic lesion of CA1 hippocampus reduced the effects of nesfatin-1 on VMH GD-responsive neuronal activity. These studies suggest that nesfatin-1 plays an important role in GD-responsive neuronal activity through interactions with CRF signaling pathways in VMH. The hippocampus may participate in the modulation of nesfatin-1-mediated effects in VMH.
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Affiliation(s)
- Hongzhen Feng
- Department of Pathophysiology, Medical College of Qingdao University, Qingdao, Shandong, PR China.
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