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Wu H, Li J, Jiang K, Li Y, Yu Z, Wang B, Zhou B, Zhang X, Tang N, Li Z. Characterization of Leptin and Leptin Receptor Gene in the Siberian Sturgeon ( Acipenser baerii): Molecular Cloning, Tissue Distribution, and Its Involvement in Feeding Regulation. Int J Mol Sci 2025; 26:1968. [PMID: 40076594 PMCID: PMC11900199 DOI: 10.3390/ijms26051968] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2024] [Revised: 02/17/2025] [Accepted: 02/21/2025] [Indexed: 03/14/2025] Open
Abstract
Leptin is an adipokine known as a regulator of feeding and metabolism in mammals. Previous studies on fish have revealed its role in food intake regulation in limited teleosts. However, its specific function in Siberian sturgeon, an ancient Chondrostei fish, remains poorly understood. This study represents the first successful cloning of sequences for leptin and leptin receptors in Siberian sturgeon, achieved using RT-PCR. The predicted leptin sequence in this species consists of 168 amino acids that exhibit low identity with other fish species, except within the Acipenseriformes order. Tissue distribution analysis revealed a high expression of Siberian sturgeon leptin mRNA in the liver and lepr mRNA in the hypothalamus. Fasting differentially affected the expression of leptin and lepr mRNA, with decreased levels in the hypothalamus and increased levels in the liver (leptin: 3-15 days; lepr: 6-15 days). Recombinant Siberian sturgeon leptin (Ssleptin) was produced via E. coli expression, and intraperitoneal injection (100 ng/g BW) significantly inhibited food intake. The anorectic effect was correlated with changes in hypothalamic gene expression, including downregulation of orexigenic factors (agrp, orexin, npy, and ghrelin) and upregulation of anorexigenic factors (pomc, mch, and insulin). Meanwhile, the peripheral administration of Ssleptin promoted the expression of resistin in the liver and concurrently increased cck and pyy mRNA levels in the valvular intestine. Furthermore, Ssleptin injection stimulated the expression of hypothalamic lepr, jak2, akt, and ampkα2 mRNA. These findings suggest that leptin plays a significant role in the feeding control of Siberian sturgeon and provide new insights into the evolutionary function of leptin in fish.
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Affiliation(s)
- Hongwei Wu
- Department of Aquaculture, College of Animal Science and Technology, Sichuan Agricultural University, No. 211 Huimin Road, Chengdu 611130, China; (H.W.)
| | - Jiamei Li
- Department of Aquaculture, College of Animal Science and Technology, Sichuan Agricultural University, No. 211 Huimin Road, Chengdu 611130, China; (H.W.)
| | - Kezhen Jiang
- Department of Aquaculture, College of Animal Science and Technology, Sichuan Agricultural University, No. 211 Huimin Road, Chengdu 611130, China; (H.W.)
| | - Yingzi Li
- Department of Aquaculture, College of Animal Science and Technology, Sichuan Agricultural University, No. 211 Huimin Road, Chengdu 611130, China; (H.W.)
| | - Zhaoxiong Yu
- Fisheries Research Institute, Sichuan Academy of Agricultural Sciences, Chengdu 611731, China
| | - Bin Wang
- Fisheries Research Institute, Sichuan Academy of Agricultural Sciences, Chengdu 611731, China
| | - Bo Zhou
- Fisheries Research Institute, Sichuan Academy of Agricultural Sciences, Chengdu 611731, China
| | - Xin Zhang
- Department of Aquaculture, College of Animal Science and Technology, Sichuan Agricultural University, No. 211 Huimin Road, Chengdu 611130, China; (H.W.)
| | - Ni Tang
- Department of Aquaculture, College of Animal Science and Technology, Sichuan Agricultural University, No. 211 Huimin Road, Chengdu 611130, China; (H.W.)
- Fisheries Research Institute, Sichuan Academy of Agricultural Sciences, Chengdu 611731, China
| | - Zhiqiong Li
- Department of Aquaculture, College of Animal Science and Technology, Sichuan Agricultural University, No. 211 Huimin Road, Chengdu 611130, China; (H.W.)
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Lonardo MS, Cacciapuoti N, Guida B, Di Lorenzo M, Chiurazzi M, Damiano S, Menale C. Hypothalamic-Ovarian axis and Adiposity Relationship in Polycystic Ovary Syndrome: Physiopathology and Therapeutic Options for the Management of Metabolic and Inflammatory Aspects. Curr Obes Rep 2024; 13:51-70. [PMID: 38172476 PMCID: PMC10933167 DOI: 10.1007/s13679-023-00531-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/27/2023] [Indexed: 01/05/2024]
Abstract
PURPOSE OF REVIEW The goal of the present review is to address the main adiposity-related alterations in Polycystic Ovary Syndrome (PCOS) focusing on hypothalamic-pituitary-ovarian (H-P-O) axis and to provide an overview of nutraceutical and pharmacological therapeutic strategies. RECENT FINDINGS Female reproduction is a complex and delicate interplay between neuroendocrine signals involving the H-P-O axis. Elements that disrupt the balance of these interactions can lead to metabolic and reproductive disorders, such as PCOS. This disorder includes menstrual, metabolic, and biochemical abnormalities as well as hyperandrogenism, oligo-anovulatory menstrual cycles, insulin resistance, and hyperleptinemia which share an inflammatory state with other chronic diseases. Moreover, as in a self-feeding cycle, high androgen levels in PCOS lead to visceral fat deposition, resulting in insulin resistance and hyperinsulinemia, further stimulating ovarian and adrenal androgen production. In fact, regardless of age and BMI, women with PCOS have more adipose tissue and less lean mass than healthy women. Excessive adiposity, especially visceral adiposity, is capable of affecting female reproduction through direct mechanisms compromising the luteal phase, and indirect mechanisms as metabolic alterations able to affect the function of the H-P-O axis. The intricate crosstalk between adiposity, inflammatory status and H-P-O axis function contributes to the main adiposity-related alterations in PCOS, and alongside currently available hormonal treatments, nutraceutical and pharmacological therapeutic strategies can be exploited to treat these alterations, in order to enable a more comprehensive synergistic and tailored treatment.
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Affiliation(s)
- Maria Serena Lonardo
- Department of Clinical Medicine and Surgery, Physiology Nutrition Unit, Federico II University of Naples, Via Sergio Pansini 5, 80131, Napoli, Italy.
| | - Nunzia Cacciapuoti
- Department of Clinical Medicine and Surgery, Physiology Nutrition Unit, Federico II University of Naples, Via Sergio Pansini 5, 80131, Napoli, Italy
| | - Bruna Guida
- Department of Clinical Medicine and Surgery, Physiology Nutrition Unit, Federico II University of Naples, Via Sergio Pansini 5, 80131, Napoli, Italy
| | - Mariana Di Lorenzo
- Department of Clinical Medicine and Surgery, Physiology Nutrition Unit, Federico II University of Naples, Via Sergio Pansini 5, 80131, Napoli, Italy
| | - Martina Chiurazzi
- Department of Clinical Medicine and Surgery, Physiology Nutrition Unit, Federico II University of Naples, Via Sergio Pansini 5, 80131, Napoli, Italy
| | - Simona Damiano
- Department of Clinical Medicine and Surgery, Physiology Nutrition Unit, Federico II University of Naples, Via Sergio Pansini 5, 80131, Napoli, Italy
| | - Ciro Menale
- Department of Clinical Medicine and Surgery, Physiology Nutrition Unit, Federico II University of Naples, Via Sergio Pansini 5, 80131, Napoli, Italy
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Boyle CA, Kola PK, Oraegbuna CS, Lei S. Leptin excites basolateral amygdala principal neurons and reduces food intake by LepRb-JAK2-PI3K-dependent depression of GIRK channels. J Cell Physiol 2024; 239:e31117. [PMID: 37683049 PMCID: PMC10920395 DOI: 10.1002/jcp.31117] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2023] [Revised: 08/08/2023] [Accepted: 08/25/2023] [Indexed: 09/10/2023]
Abstract
Leptin is an adipocyte-derived hormone that modulates food intake, energy balance, neuroendocrine status, thermogenesis, and cognition. Whereas a high density of leptin receptors has been detected in the basolateral amygdala (BLA) neurons, the physiological functions of leptin in the BLA have not been determined yet. We found that application of leptin excited BLA principal neurons by activation of the long form leptin receptor, LepRb. The LepRb-elicited excitation of BLA neurons was mediated by depression of the G protein-activated inwardly rectifying potassium (GIRK) channels. Janus Kinase 2 (JAK2) and phosphoinositide 3-kinase (PI3K) were required for leptin-induced excitation of BLA neurons and depression of GIRK channels. Microinjection of leptin into the BLA reduced food intake via activation of LepRb, JAK2, and PI3K. Our results may provide a cellular and molecular mechanism to explain the physiological roles of leptin in vivo.
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Affiliation(s)
- Cody A. Boyle
- Department of Biomedical Sciences, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND58203, USA
| | - Phani K. Kola
- Department of Biomedical Sciences, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND58203, USA
| | - Chidiebele S. Oraegbuna
- Department of Biomedical Sciences, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND58203, USA
| | - Saobo Lei
- Department of Biomedical Sciences, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND58203, USA
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Sharma Y, Galvão AM. Maternal obesity and ovarian failure: is leptin the culprit? Anim Reprod 2023; 19:e20230007. [PMID: 36855701 PMCID: PMC9968511 DOI: 10.1590/1984-3143-ar2023-0007] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2023] [Accepted: 01/24/2023] [Indexed: 02/22/2023] Open
Abstract
At the time of its discovery and characterization in 1994, leptin was mostly considered a metabolic hormone able to regulate body weight and energy homeostasis. However, in recent years, a great deal of literature has revealed leptin's pleiotropic nature, through its involvement in numerous physiological contexts including the regulation of the female reproductive tract and ovarian function. Obesity has been largely associated with infertility, and leptin signalling is known to be dysregulated in the ovaries of obese females. Hence, the disruption of ovarian leptin signalling was shown to contribute to the pathophysiology of ovarian failure in obese females, affecting transcriptional programmes in the gamete and somatic cells. This review attempts to uncover the underlying mechanisms contributing to female infertility associated with obesity, as well as to shed light on the role of leptin in the metabolic dysregulation within the follicle, the effects on the oocyte epigenome, and the potential long-term consequence to embryo programming.
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Affiliation(s)
- Yashaswi Sharma
- Institute of Animal Reproduction and Food Research of PAS, Department of Reproductive Immunology and Pathology, Olsztyn, Poland
| | - António Miguel Galvão
- Institute of Animal Reproduction and Food Research of PAS, Department of Reproductive Immunology and Pathology, Olsztyn, Poland,Babraham Institute, Epigenetics Programme, Cambridge, United Kingdom UK,Centre for Trophoblast Research, University of Cambridge, Cambridge, United Kingdom UK,Corresponding author: ;
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Mlyczyńska E, Kieżun M, Kurowska P, Dawid M, Pich K, Respekta N, Daudon M, Rytelewska E, Dobrzyń K, Kamińska B, Kamiński T, Smolińska N, Dupont J, Rak A. New Aspects of Corpus Luteum Regulation in Physiological and Pathological Conditions: Involvement of Adipokines and Neuropeptides. Cells 2022; 11:957. [PMID: 35326408 PMCID: PMC8946127 DOI: 10.3390/cells11060957] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2022] [Revised: 02/28/2022] [Accepted: 03/08/2022] [Indexed: 11/17/2022] Open
Abstract
The corpus luteum is a small gland of great importance because its proper functioning determines not only the appropriate course of the estrous/menstrual cycle and embryo implantation, but also the subsequent maintenance of pregnancy. Among the well-known regulators of luteal tissue functions, increasing attention is focused on the role of neuropeptides and adipose tissue hormones-adipokines. Growing evidence points to the expression of these factors in the corpus luteum of women and different animal species, and their involvement in corpus luteum formation, endocrine function, angiogenesis, cells proliferation, apoptosis, and finally, regression. In the present review, we summarize the current knowledge about the expression and role of adipokines, such as adiponectin, leptin, apelin, vaspin, visfatin, chemerin, and neuropeptides like ghrelin, orexins, kisspeptin, and phoenixin in the physiological regulation of the corpus luteum function, as well as their potential involvement in pathologies affecting the luteal cells that disrupt the estrous cycle.
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Affiliation(s)
- Ewa Mlyczyńska
- Laboratory of Physiology and Toxicology of Reproduction, Institute of Zoology and Biomedical Research, Jagiellonian University in Krakow, 30-387 Krakow, Poland; (E.M.); (P.K.); (M.D.); (K.P.); (N.R.)
| | - Marta Kieżun
- Department of Animal Anatomy and Physiology, Faculty of Biology and Biotechnology, University of Warmia and Mazury in Olsztyn, 10-719 Olsztyn, Poland; (M.K.); (E.R.); (B.K.); (T.K.); (N.S.)
| | - Patrycja Kurowska
- Laboratory of Physiology and Toxicology of Reproduction, Institute of Zoology and Biomedical Research, Jagiellonian University in Krakow, 30-387 Krakow, Poland; (E.M.); (P.K.); (M.D.); (K.P.); (N.R.)
| | - Monika Dawid
- Laboratory of Physiology and Toxicology of Reproduction, Institute of Zoology and Biomedical Research, Jagiellonian University in Krakow, 30-387 Krakow, Poland; (E.M.); (P.K.); (M.D.); (K.P.); (N.R.)
| | - Karolina Pich
- Laboratory of Physiology and Toxicology of Reproduction, Institute of Zoology and Biomedical Research, Jagiellonian University in Krakow, 30-387 Krakow, Poland; (E.M.); (P.K.); (M.D.); (K.P.); (N.R.)
| | - Natalia Respekta
- Laboratory of Physiology and Toxicology of Reproduction, Institute of Zoology and Biomedical Research, Jagiellonian University in Krakow, 30-387 Krakow, Poland; (E.M.); (P.K.); (M.D.); (K.P.); (N.R.)
| | - Mathilde Daudon
- Unité Physiologie de la Reproduction et des Comportements, French National Institute for Agriculture, Food, and Environment, 37380 Nouzilly, France; (M.D.); (J.D.)
| | - Edyta Rytelewska
- Department of Animal Anatomy and Physiology, Faculty of Biology and Biotechnology, University of Warmia and Mazury in Olsztyn, 10-719 Olsztyn, Poland; (M.K.); (E.R.); (B.K.); (T.K.); (N.S.)
| | - Kamil Dobrzyń
- Department of Zoology, Faculty of Biology and Biotechnology, University of Warmia and Mazury in Olsztyn, 10-719 Olsztyn, Poland;
| | - Barbara Kamińska
- Department of Animal Anatomy and Physiology, Faculty of Biology and Biotechnology, University of Warmia and Mazury in Olsztyn, 10-719 Olsztyn, Poland; (M.K.); (E.R.); (B.K.); (T.K.); (N.S.)
| | - Tadeusz Kamiński
- Department of Animal Anatomy and Physiology, Faculty of Biology and Biotechnology, University of Warmia and Mazury in Olsztyn, 10-719 Olsztyn, Poland; (M.K.); (E.R.); (B.K.); (T.K.); (N.S.)
| | - Nina Smolińska
- Department of Animal Anatomy and Physiology, Faculty of Biology and Biotechnology, University of Warmia and Mazury in Olsztyn, 10-719 Olsztyn, Poland; (M.K.); (E.R.); (B.K.); (T.K.); (N.S.)
| | - Joelle Dupont
- Unité Physiologie de la Reproduction et des Comportements, French National Institute for Agriculture, Food, and Environment, 37380 Nouzilly, France; (M.D.); (J.D.)
| | - Agnieszka Rak
- Laboratory of Physiology and Toxicology of Reproduction, Institute of Zoology and Biomedical Research, Jagiellonian University in Krakow, 30-387 Krakow, Poland; (E.M.); (P.K.); (M.D.); (K.P.); (N.R.)
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Zhu J, Chen F, Luo L, Wu W, Dai J, Zhong J, Lin X, Chai C, Ding P, Liang L, Wang S, Ding X, Chen Y, Wang H, Qiu J, Wang F, Sun C, Zeng Y, Fang J, Jiang X, Liu P, Tang G, Qiu X, Zhang X, Ruan Y, Jiang S, Li J, Zhu S, Xu X, Li F, Liu Z, Cao G, Chen D. Single-cell atlas of domestic pig cerebral cortex and hypothalamus. Sci Bull (Beijing) 2021; 66:1448-1461. [PMID: 36654371 DOI: 10.1016/j.scib.2021.04.002] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2020] [Revised: 11/07/2020] [Accepted: 03/12/2021] [Indexed: 01/20/2023]
Abstract
The brain of the domestic pig (Sus scrofa domesticus) has drawn considerable attention due to its high similarities to that of humans. However, the cellular compositions of the pig brain (PB) remain elusive. Here we investigated the single-nucleus transcriptomic profiles of five regions of the PB (frontal lobe, parietal lobe, temporal lobe, occipital lobe, and hypothalamus) and identified 21 cell subpopulations. The cross-species comparison of mouse and pig hypothalamus revealed the shared and specific gene expression patterns at the single-cell resolution. Furthermore, we identified cell types and molecular pathways closely associated with neurological disorders, bridging the gap between gene mutations and pathogenesis. We reported, to our knowledge, the first single-cell atlas of domestic pig cerebral cortex and hypothalamus combined with a comprehensive analysis across species, providing extensive resources for future research regarding neural science, evolutionary developmental biology, and regenerative medicine.
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Affiliation(s)
- Jiacheng Zhu
- College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China; BGI-Shenzhen, Shenzhen 518083, China
| | - Fang Chen
- BGI-Shenzhen, Shenzhen 518083, China; MGI, BGI-Shenzhen, Shenzhen 518083, China
| | - Lihua Luo
- College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China; BGI-Shenzhen, Shenzhen 518083, China
| | - Weiying Wu
- BGI-Shenzhen, Shenzhen 518083, China; Department of Neurobiology, NHC and CAMS Key Laboratory of Medical Neurobiology, School of Brain Science and Brian Medicine, and the MOE Frontier Science Center for Brain Research and Brain-Machine Integration, Zhejiang University School of Medicine, Hangzhou 310031, China
| | - Jinxia Dai
- State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, China; College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China
| | - Jixing Zhong
- School of Biological Science & Medical Engineering, Southeast University, Nanjing 210096, China
| | - Xiumei Lin
- College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China; BGI-Shenzhen, Shenzhen 518083, China
| | - Chaochao Chai
- College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China; BGI-Shenzhen, Shenzhen 518083, China
| | - Peiwen Ding
- College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China; BGI-Shenzhen, Shenzhen 518083, China
| | - Langchao Liang
- College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China; BGI-Shenzhen, Shenzhen 518083, China
| | - Shiyou Wang
- College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China; BGI-Shenzhen, Shenzhen 518083, China
| | - Xiangning Ding
- College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China; BGI-Shenzhen, Shenzhen 518083, China
| | - Yin Chen
- College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China; BGI-Shenzhen, Shenzhen 518083, China
| | - Haoyu Wang
- College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China; BGI-Shenzhen, Shenzhen 518083, China
| | - Jiaying Qiu
- College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China; BGI-Shenzhen, Shenzhen 518083, China
| | | | - Chengcheng Sun
- College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China; BGI-Shenzhen, Shenzhen 518083, China; School of Basic Medicine, Qingdao University, Qingdao 266071, China
| | - Yuying Zeng
- College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China; BGI-Shenzhen, Shenzhen 518083, China; College of Life Science, South China Agricultural University, Guangzhou 510642, China
| | - Jian Fang
- BGI-Shenzhen, Shenzhen 518083, China
| | - Xiaosen Jiang
- College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China; BGI-Shenzhen, Shenzhen 518083, China
| | - Ping Liu
- BGI-Shenzhen, Shenzhen 518083, China; MGI, BGI-Shenzhen, Shenzhen 518083, China
| | - Gen Tang
- Shenzhen Children's Hospital, Shenzhen 518083, China
| | - Xin Qiu
- Shenzhen Children's Hospital, Shenzhen 518083, China
| | | | - Yetian Ruan
- Research Center for Translational Medicine, East Hospital, Tongji University School of Medicine, Shanghai 200120, China
| | | | | | - Shida Zhu
- BGI-Shenzhen, Shenzhen 518083, China
| | - Xun Xu
- BGI-Shenzhen, Shenzhen 518083, China
| | - Fang Li
- Research Center for Translational Medicine, East Hospital, Tongji University School of Medicine, Shanghai 200120, China
| | - Zhongmin Liu
- Research Center for Translational Medicine, East Hospital, Tongji University School of Medicine, Shanghai 200120, China
| | - Gang Cao
- State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, China; College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China; College of Biomedicine and Health, Huazhong Agricultural University, Wuhan 430070, China.
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Barbe A, Kurowska P, Mlyczyńska E, Ramé C, Staub C, Venturi E, Billon Y, Rak A, Dupont J. Adipokines expression profiles in both plasma and peri renal adipose tissue in Large White and Meishan sows: A possible involvement in the fattening and the onset of puberty. Gen Comp Endocrinol 2020; 299:113584. [PMID: 32827511 DOI: 10.1016/j.ygcen.2020.113584] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2020] [Revised: 07/16/2020] [Accepted: 08/08/2020] [Indexed: 01/15/2023]
Abstract
In pig, backfat deposition is strongly related to the growth and reproductive performance. However, the molecular regulatory mechanisms of adipose tissue are not clearly understood. Adipose tissue is now recognized as an important endocrine organ that secretes a variety of factors including adipokines. However, the regulation of expression pattern of these adipokines in both plasma and visceral white adipose tissue (WAT) in lean and fat pig is unclear. In the present study, we used two representative porcine breeds (Large White, LW; Meishan, MS) with contrasting backfat thickness and sexual maturity age. Using specific ELISA assays, we determined the plasma profile of eight adipokines, leptin, adiponectin, visfatin, apelin, chemerin, resistin, omentin and vaspin in LW and MS sows. By RT-qPCR and western-blot we also investigated the mRNA and protein levels of these adipokines and their cognate receptors (LEPR, ADIPOR1, ADIPOR2, CMKLR1, CCRL2, GPR1, APLNR, TLR4, ROR1, CAP1 and HSPA5) in the peri renal WAT, respectively. At both plasma and peri renal WAT level, we found that the amounts of leptin, chemerin, resistin and vaspin were higher whereas those of adiponectin and omentin were lower in MS than LW sows. Plasma and adipose tissue visfatin and apelin levels were not different between the two breeds. Moreover, we noted that the variations of peri renal WAT adipokines observed between MS and LW were similar at the protein and mRNA level except for chemerin and apelin suggesting post-transcriptional modifications for these two adipokines. Finally, among the eight adipokines studied, we showed that only the plasma concentrations of leptin and chemerin were positively and those of adiponectin, negatively associated with the thickness of fat and opposite correlation was found for the onset of puberty in both LW and MS animals. Taken together, these results support a potential involvement of adipokines in WAT regulation and its link with the onset of the puberty in sows.
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Affiliation(s)
- Alix Barbe
- INRAE UMR85 Physiologie de la Reproduction et des Comportements, F-37380 Nouzilly, France; CNRS UMR7247 Physiologie de la Reproduction et des Comportements, F-37380 Nouzilly, France; Université François Rabelais de Tours, F-37041 Tours, France; IFCE, F-37380 Nouzilly, France
| | - Patrycja Kurowska
- Department of Physiology and Toxicology of Reproduction, Institute of Zoology and Biomedical Research, Jagiellonian University in Krakow, 30 387 Krakow, Poland
| | - Ewa Mlyczyńska
- Department of Physiology and Toxicology of Reproduction, Institute of Zoology and Biomedical Research, Jagiellonian University in Krakow, 30 387 Krakow, Poland
| | - Christelle Ramé
- INRAE UMR85 Physiologie de la Reproduction et des Comportements, F-37380 Nouzilly, France; CNRS UMR7247 Physiologie de la Reproduction et des Comportements, F-37380 Nouzilly, France; Université François Rabelais de Tours, F-37041 Tours, France; IFCE, F-37380 Nouzilly, France
| | - Christophe Staub
- INRAE - Unité Expérimentale de Physiologie Animale de l'Orfrasière UEPAO 1297, F 37380 Nouzilly, France
| | - Eric Venturi
- INRAE - Unité Expérimentale de Physiologie Animale de l'Orfrasière UEPAO 1297, F 37380 Nouzilly, France
| | - Yvon Billon
- INRAE-Pig Innovative Breeding Experimental Facility, Le Magneraud, 17000 Surgères, France
| | - Agnieszka Rak
- Department of Physiology and Toxicology of Reproduction, Institute of Zoology and Biomedical Research, Jagiellonian University in Krakow, 30 387 Krakow, Poland
| | - Joëlle Dupont
- INRAE UMR85 Physiologie de la Reproduction et des Comportements, F-37380 Nouzilly, France; CNRS UMR7247 Physiologie de la Reproduction et des Comportements, F-37380 Nouzilly, France; Université François Rabelais de Tours, F-37041 Tours, France; IFCE, F-37380 Nouzilly, France.
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Lents CA, Lindo AN, Hileman SM, Nonneman DJ. Physiological and genomic insight into neuroendocrine regulation of puberty in gilts. Domest Anim Endocrinol 2020; 73:106446. [PMID: 32199704 DOI: 10.1016/j.domaniend.2020.106446] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2019] [Revised: 01/27/2020] [Accepted: 01/29/2020] [Indexed: 12/20/2022]
Abstract
The timing of pubertal attainment in gilts is a critical factor for pork production and is an early indicator of future reproductive potential. Puberty, defined as age at first standing estrus in the presence of a boar, is brought about by an escape from estrogen inhibition of the GnRH pulse generator, which allows for increasing LH pulses leading to the onset of cyclicity. The biological mechanisms that control the timing of these events is related to decreasing inhibitory signals with a concomitant increase in stimulatory signals within the hypothalamus. The roles of gamma-aminobutyric acid, endogenous opioid peptides, and gonadotropin-inhibitory hormone in negatively regulating gonadotropin secretion in gilts is explored. Developmental changes in stimulatory mechanisms of glutamatergic and kisspeptin neurons are important for increased LH pulsatility required for the occurrence of puberty in pigs. Age at first estrus of gilts is metabolically gated, and numerous metabolites, metabolic hormones, and appetite-regulating neurotransmitters have been implicated in the nutritional regulation of gonadotropin secretion. Leptin is an important metabolic signal linking body energy reserves with age at puberty in gilts. Leptin acting through neuropeptide Y and proopiomelanocortin neurons in the hypothalamus has important impacts on the function of the reproductive neurosecretory axis of gilts. Age at puberty in swine is heritable, and genomic analyses reveal it to be a polygenic trait. Genome-wide association studies for pubertal age in gilts have revealed several genomic regions in common with those identified for age at menarche in humans. Candidate genes have been identified that have important functions in growth and adiposity. Numerous genes regulating hypothalamic neuronal function, gonadotropes in the adenohypophysis, and ovarian follicular development have been identified and illustrate the complex maturational changes occurring in the hypothalamic-pituitary-ovarian axis during puberty in gilts.
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Affiliation(s)
- C A Lents
- USDA, ARS, U.S. Meat Animal Research Center, Reproduction Research Unit, Clay Center, NE 68966-0166, USA.
| | - A N Lindo
- Department of Physiology and Pharmacology, West Virginia University, Morgantown, WV 26506-9600, USA
| | - S M Hileman
- Department of Physiology and Pharmacology, West Virginia University, Morgantown, WV 26506-9600, USA
| | - D J Nonneman
- USDA, ARS, U.S. Meat Animal Research Center, Reproduction Research Unit, Clay Center, NE 68966-0166, USA
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Magzoub A, Al-Ayed M, Shaikh IA, Habeeb MS, Al-Shaibary K, Shalayel M. Leptin induces a contracting effect on guinea pig tracheal smooth muscle via the Ob-R receptor mechanism: novel evidence. Can J Physiol Pharmacol 2020; 98:810-817. [PMID: 32687729 DOI: 10.1139/cjpp-2019-0605] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
The purpose of this study was to explore the potential contracting effect of leptin on isolated guinea pig tracheal smooth muscle (TSM), the possible mechanism, and the impact of epithelium denudation or allergen sensitization, respectively. An in vitro experiment investigated the effect of leptin at a concentration of 250-1000 nmol/L on isolated guinea pig TSM with an intact or denuded epithelium. Ovalbumin and IgE were used to test the impact of active and passive sensitization. The isolated TSM strips were incubated in Krebs solution and aerated with carbogen (95% O2 and 5% CO2) via an automated tissue organ bath system (n = 4 for each group). Isometric contractions were recorded digitally using iox2 data acquisition software. The possible mechanism of leptin-induced TSM contraction was examined by preincubation with leptin receptor (Ob-R) antagonist. Leptin had significant concentration-dependent contraction effects on guinea pig TSM (p < 0.05). Epithelium denuding and active or passive sensitization significantly increased the potency of the leptin. Preincubation with a leptin receptor (Ob-R) antagonist significantly reduced the contraction effects, suggesting an Ob-R-mediated mechanism. Leptin had a contracting effect on airway smooth muscles potentiated by either epithelium denuding or sensitization, and the Ob-R mechanism was a possible effect mediator.
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Affiliation(s)
- Aamir Magzoub
- Department of Physiology, College of Medicine, Najran University, Saudi Arabia
| | - Mohammed Al-Ayed
- Department of Pediatrics, College of Medicine, Najran University, Saudi Arabia
| | - Ibrahim Ahmed Shaikh
- Department of Pharmacology, College of Pharmacy, Najran University, Saudi Arabia
| | | | - Khalid Al-Shaibary
- Department of Pediatrics, College of Medicine, Najran University, Saudi Arabia
| | - Mohammed Shalayel
- Department of Biochemistry, College of Medicine, Najran University, Saudi Arabia
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10
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Raza SHA, Liu GY, Zhou L, Gui LS, Khan R, Jinmeng Y, Chugang M, Schreurs NM, Ji R, Zan L. Detection of polymorphisms in the bovine leptin receptor gene affects fat deposition in two Chinese beef cattle breeds. Gene 2020; 758:144957. [PMID: 32683081 DOI: 10.1016/j.gene.2020.144957] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2020] [Revised: 06/12/2020] [Accepted: 07/13/2020] [Indexed: 12/01/2022]
Abstract
Leptin receptor (LEPR) gene play a pivotal role in the regulation of fat deposition and energy homeostasis. This study investigated the presence and frequency of polymorphisms of bovine LEPR gene and determine whether the polymorphisms are associated with the fat deposition in two Chinese beef cattle breeds. Quantitative real-time polymerase chain reactions identified that the expression of LEPR gene was highest in the liver and subcutaneous fat. Four single nucleotide polymorphisms (SNPs) were identified including g.24169C > T, g.24256T > A, g.24267 G > C and g.24413T > A. A greater backfat thickness was associated with the AA genotype of g.24256T > A compared to the TT genotype. A greater intramuscular fat content was associated with the GG genotype of g.24267 G > C compared to the CC genotype. Both g.24169C > T and g.24413T > A were not correlated with fat deposition. These results indicated that the SNP g.24256T > A and g.24267 G > C of LEPR gene may be useful markers for genetic improvement of fat deposition in Chinese beef cattle breeds.
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Affiliation(s)
- Sayed Haidar Abbas Raza
- College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, PR China; National Beef Cattle Improvement Center, Northwest A&F University, 712100 Yangling, Shaanxi, PR China.
| | - Gui-Yao Liu
- Poyang Lake Eco-economy Research Center, Jiujiang University, Jiujiang, Jiangxi Province 332005, PR China
| | - Li Zhou
- State Key Laboratory of Plateau Ecology and Agriculture, Qinghai University, Xining, Qinghai Province 810016, PR China
| | - Lin-Sheng Gui
- State Key Laboratory of Plateau Ecology and Agriculture, Qinghai University, Xining, Qinghai Province 810016, PR China
| | - Rajwali Khan
- College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, PR China
| | - Yang Jinmeng
- College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, PR China
| | - Mei Chugang
- College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, PR China
| | - Nicola M Schreurs
- Animal Science, School of Agriculture and Environment, Massey University, Palmerston North, New Zealand
| | - Rodany Ji
- Utah State University, School of Animal Dairy and Veterinary Sciences, Logan, UT, 84322, USA
| | - Linsen Zan
- College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, PR China; National Beef Cattle Improvement Center, Northwest A&F University, 712100 Yangling, Shaanxi, PR China.
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11
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Kasacka I, Piotrowska Ż, Niezgoda M, Łebkowski W. Differences in leptin biosynthesis in the stomach and in serum leptin level between men and women. J Gastroenterol Hepatol 2019; 34:1922-1928. [PMID: 31017682 DOI: 10.1111/jgh.14688] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2019] [Accepted: 04/12/2019] [Indexed: 01/28/2023]
Abstract
BACKGROUND AND AIM Although the stomach has been identified as an important source of leptin, the detailed biosynthesis sites of leptin in human gastrointestinal tract have not been fully elucidated. The study objective was to compare leptin distribution and expression in the stomach and its serum level between healthy men and women. METHODS Nineteen subjects (organ donors; 10 men and 9 women) with normal gastric mucosa histology were recruited. Research material contained gastric samples from the cardia, fundus, and pyloric regions. Gastric mucosa leptin content and leptin gene expression were determined by immunohistochemistry and real-time polymerase chain reaction method. Plasma leptin level was measured using ELISA method. RESULTS In the stomach of healthy adult subjects, leptin-immunoreactive cells were mainly found in the fundus, and the number of immunoreactive cells was higher in women than in men. Leptin-containing cells were less numerous in the cardia and pylorus mucosa. Similarly, leptin gene expression was the highest in the fundus and higher in women than in men. Serum leptin level was higher in women than in men and was found to correlate positively with body mass index and weight in both sexes. A negative correlation between leptin level and age was noted in women, but not in men. CONCLUSIONS The current study is the first to provide evidence for the presence of leptin-containing cells in all segments of the human stomach. The differences in gastric leptin biosynthesis and serum leptin levels between men and women suggest that leptin secretion can be controlled by sex hormones or other unknown factors.
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Affiliation(s)
- Irena Kasacka
- Department of Histology and Cytophysiology, Medical University of Białystok, Białystok, Poland
| | - Żaneta Piotrowska
- Department of Histology and Cytophysiology, Medical University of Białystok, Białystok, Poland
| | - Michał Niezgoda
- Department of Histology and Cytophysiology, Medical University of Białystok, Białystok, Poland
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12
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Furigo IC, de Souza GO, Teixeira PDS, Guadagnini D, Frazão R, List EO, Kopchick JJ, Prada PO, Donato J. Growth hormone enhances the recovery of hypoglycemia via ventromedial hypothalamic neurons. FASEB J 2019; 33:11909-11924. [PMID: 31366244 DOI: 10.1096/fj.201901315r] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Growth hormone (GH) is secreted during hypoglycemia, and GH-responsive neurons are found in brain areas containing glucose-sensing neurons that regulate the counter-regulatory response (CRR). However, whether GH modulates the CRR to hypoglycemia via specific neuronal populations is currently unknown. Mice carrying ablation of GH receptor (GHR) either in leptin receptor (LepR)- or steroidogenic factor-1 (SF1)-expressing cells were studied. We also investigated the importance of signal transducer and activator of transcription 5 (STAT5) signaling in SF1 cells for the CRR. GHR ablation in LepR cells led to impaired capacity to recover from insulin-induced hypoglycemia and to a blunted CRR caused by 2-deoxy-d-glucose (2DG) administration. GHR inactivation in SF1 cells, which include ventromedial hypothalamic neurons, also attenuated the CRR. The reduced CRR was prevented by parasympathetic blockers. Additionally, infusion of 2DG produced an abnormal hyperactivity of parasympathetic preganglionic neurons, whereas the 2DG-induced activation of anterior bed nucleus of the stria terminalis neurons was reduced in mice without GHR in SF1 cells. Mice carrying ablation of Stat5a/b genes in SF1 cells showed no defects in the CRR. In summary, GHR expression in SF1 cells is required for a normal CRR, and these effects are largely independent of STAT5 pathway.-Furigo, I. C., de Souza, G. O., Teixeira, P. D. S., Guadagnini, D., Frazão, R., List, E. O., Kopchick, J. J., Prada, P. O., Donato, J., Jr. Growth hormone enhances the recovery of hypoglycemia via ventromedial hypothalamic neurons.
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Affiliation(s)
- Isadora C Furigo
- Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
| | - Gabriel O de Souza
- Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
| | - Pryscila D S Teixeira
- Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
| | - Dioze Guadagnini
- School of Applied Sciences, State University of Campinas, Limeira, Brazil
| | - Renata Frazão
- Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
| | - Edward O List
- Edison Biotechnology Institute and Heritage College of Osteopathic Medicine, Ohio University, Athens, Ohio, USA
| | - John J Kopchick
- Edison Biotechnology Institute and Heritage College of Osteopathic Medicine, Ohio University, Athens, Ohio, USA
| | - Patricia O Prada
- School of Applied Sciences, State University of Campinas, Limeira, Brazil
| | - Jose Donato
- Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
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Abstract
Consumers' demand of leaner meat products is a challenge. Although betaine and conjugated linoleic acid (CLA) have the potential to decrease porcine adipose tissue, their mode of action is poorly understood. The aim of the study was to determine the lipolytic effect of betaine and CLA in the adipose tissue of Iberian pigs. Adipose tissue explants from five pigs (38 kg BW) were prepared from dorsal subcutaneous adipose tissue samples and cultivated for 2 h (acute experiments) or 72 h (chronic experiments). Treatments included 100 µM linoleic acid (control), 100 µM trans-10, cis-12 CLA, 100 µM linoleic acid + 1 mM betaine and 100 µM trans-10, cis-12 CLA + 1 mM betaine (CLABET). To examine the ability of betaine or CLA to inhibit insulin's suppression of isoproterenol-stimulated lipolysis, test medium was amended with 1 µM isoproterenol ±10 nM insulin. Media glycerol was measured at the end of the incubations. Acute lipolysis (2 h) was increased by CLA and CLABET (85% to 121%; P < 0.05) under basal conditions. When lipolysis was stimulated with isoproterenol (1090%), acute exposure to betaine tended to increase (13%; P = 0.071), while CLA and CLABET increased (14% to 18%; P < 0.05) isoproterenol-stimulated lipolysis compared with control. When insulin was added to isoproterenol-stimulated explants, lipolytic rate was decreased by 50% (P < 0.001). However, supplementation of betaine to the insulin + isoproterenol-containing medium tended to increase (P = 0.07), while CLABET increased (45%; P < 0.05) lipolysis, partly counteracting insulin inhibition. When culture was extended for 72 h, CLA decreased lipolysis under basal conditions (18%; P < 0.05) with no effect of betaine and CLABET (P > 0.10). When lipolysis was stimulated by isoproterenol (125% increase in rate compared with basal), CLA and CLABET decreased glycerol release (27%; P < 0.001) compared with control (isoproterenol alone). When insulin was added to isoproterenol-stimulated explants, isoproterenol stimulation of lipolysis was completely blunted and neither betaine nor CLA altered the inhibitory effect of insulin on lipolysis. Isoproterenol, and especially isoproterenol + insulin, stimulated leptin secretion compared with basal conditions (68% and 464%, respectively; P < 0.001), with no effect of CLA or betaine (P > 0.10). CLA decreased leptin release (25%; P < 0.001) when insulin was present in the media, partially inhibiting insulin stimulation of leptin release. In conclusion, betaine and CLA produced a biphasic response regarding lipolysis so that glycerol release was increased in acute conditions, while CLA decreased glycerol release and betaine had no effect in chronic conditions. Furthermore, CLA and CLABET indirectly increased lipolysis by reducing insulin-mediated inhibition of lipolysis during acute conditions.
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14
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15
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Ye C, Wang R, Wang M, Huang Z, Tang C. Leptin alleviates intestinal mucosal barrier injury and inflammation in obese mice with acute pancreatitis. Int J Obes (Lond) 2018; 42:1471-1479. [PMID: 29934609 DOI: 10.1038/s41366-018-0125-y] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2017] [Revised: 04/16/2018] [Accepted: 04/20/2018] [Indexed: 02/05/2023]
Abstract
BACKGROUND/OBJECTIVES Obesity is an independent risk factor for severe acute pancreatitis (AP). Leptin plays an important role in energy homeostasis. It has been reported that leptin might also participate in the regulation of the intestinal mucosal barrier and inflammatory response. This study aimed to evaluate the effects of leptin on the intestinal mucosal barrier and inflammatory injury in obese mice with AP. SUBJECTS/METHODS AP was induced in leptin-deficient (ob/ob) or wild type (WT) mice by peritoneal injection of caerulein. The animals were divided into 4 groups: WT mice with or without exogenous leptin injection and ob/ob mice with or without leptin treatment. The inflammatory scoring of the pancreas and intestine were evaluated. Intestinal permeability, ileal interleukin (IL)-6 and IL-1β, proliferation, apoptosis and intestinal expression levels of claudin-1 and occludin were measured. RESULTS Pancreatic pathologic scores (8.50 ± 0.96 vs. 3.78 ± 1.35, p < 0.001), pancreatic levels of IL-6 (8.34 ± 3.21 ng/mg vs. 4.99 ± 0.53 ng/mg, p = 0.022), intestinal oedema scores (2.25 ± 0.46 vs. 1.14 ± 0.69, p = 0.001) and intestinal permeability to FD4 (0.78 ± 0.06 μg/ml vs. 0.53 ± 0.11 μg/ml, p < 0.001) were significantly higher in ob/ob mice than those in WT mice. Leptin replacement in ob/ob mice greatly improved the intestinal permeability (FD4 0.66 ± 0.03 μg/ml, vs. 0.78 ± 0.06 μg/ml, p = 0.012), increased the ileal expression of claudin-1(1.07 ± 0.08 vs. 0.83 ± 0.07 relative densitometry, p = 0.001) and reduced intestinal IL-6 and IL-1β to levels comparable to those in WT mice. The pancreatic level of IL-6 in ob/ob mice treated with leptin was also significantly decreased relative to that of untreated ob/ob mice (4.45 ± 1.71 ng/mg vs. 8.34 ± 3.21 ng/mg, p = 0.010). CONCLUSIONS Obesity may aggravate intestinal inflammation and increase intestinal permeability under the condition of acute pancreatitis. Exogenous leptin supplementation was in favour of anti-inflammation and improvement of intestinal mucosal barrier.
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Affiliation(s)
- Cheng Ye
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China.,Division of Peptides Related with Human Diseases, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Rui Wang
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China.,Division of Peptides Related with Human Diseases, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Mojin Wang
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Zhiyin Huang
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China.,Division of Peptides Related with Human Diseases, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Chengwei Tang
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China. .,Division of Peptides Related with Human Diseases, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
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Phoophitphong D, Srisuwatanasagul S, Tummaruk P. Leptin Immunohistochemical Staining in the Porcine Ovary. Anat Histol Embryol 2017; 46:334-341. [DOI: 10.1111/ahe.12274] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2016] [Accepted: 04/03/2017] [Indexed: 11/28/2022]
Affiliation(s)
- D. Phoophitphong
- Department of Obstetrics, Gynaecology and Reproduction; Faculty of Veterinary Science; Chulalongkorn University; Bangkok 10330 Thailand
- Department of Veterinary Technology; Faculty of Veterinary Technology; Kasetsart University; Bangkok 10900 Thailand
| | - S. Srisuwatanasagul
- Department of Anatomy; Faculty of Veterinary Science; Chulalongkorn University; Bangkok 10330 Thailand
| | - P. Tummaruk
- Department of Obstetrics, Gynaecology and Reproduction; Faculty of Veterinary Science; Chulalongkorn University; Bangkok 10330 Thailand
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Anderson LL, Jeftinija S, Scanes CG. Growth Hormone Secretion: Molecular and Cellular Mechanisms and In Vivo Approaches. Exp Biol Med (Maywood) 2016; 229:291-302. [PMID: 15044712 DOI: 10.1177/153537020422900403] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Growth hormone (GH) release is under the direct control of hypothalamic releasing hormones, some being also produced peripherally. The role of these hypothalamic factors has been understood by in vitro studies together with such in vivo approaches as stalk sectioning. Secretion of GH is stimulated by GH-releasing hormone (GHRH) and ghrelin (acting via the GH secretagogue [GHS] receptor [GHSR]), and inhibited by somatostatin (SRIF). Other peptides/proteins influence GH secretion, at least in some species. The cellular mechanism by which the releasing hormones affect GH secretion from the somatotrope requires specific signal transduction systems (cAMP and/or calcium influx and/or mobilization of intracellular calcium) and/or tyrosine kinase(s) and/or nitric oxide (NO)/cGMP. At the subcellular level, GH release (at least in response to GHS) is accomplished by the following. The GH-containing secretory granules are moved close to the cell surface. There is then transient fusion of the secretory granules with the fusion pores in the multiple secretory pits in the somatotrope cell surface.
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Affiliation(s)
- Lloyd L Anderson
- Department of Animal Science, Iowa State University, Ames, Iowa 50011, USA.
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18
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McDuffie IA, Akhter N, Childs GV. Regulation of Leptin mRNA and Protein Expression in Pituitary Somatotropes. J Histochem Cytochem 2016; 52:263-73. [PMID: 14729878 DOI: 10.1177/002215540405200214] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Leptin, the ob protein, regulates food intake and satiety and can be found in the anterior pituitary. Leptin antigens and mRNA were studied in the anterior pituitary (AP) cells of male and female rats to learn more about its regulation. Leptin antigens were found in over 40% of cells in diestrous or proestrous female rats and in male rats. Lower percentages of AP cells were seen in the estrous population (21 ± 7%). During peak expression of antigens, co-expression of leptin and growth hormone (GH) was found in 27 ± 4% of AP cells. Affinity cytochemistry studies detected 24 ± 3% of AP cells with leptin proteins and growth hormone releasing hormone (GHRH) receptors. These data suggested that somatotropes were a significant source of leptin. To test regulatory factors, estrous and diestrous AP populations were treated with estrogen (100 pM) and/or GHRH (2 nM) to learn if either would increase leptin expression in GH cells. To rule out the possibility that the immunoreactive leptin was bound to receptors in somatotropes, leptin mRNA was also detected by non-radioactive in situ hybridization in this group of cells. In estrous female rats, 39 ± 0.9% of AP cells expressed leptin mRNA, indicating that the potential for leptin production was greater than predicted from the immunolabeling. Estrogen and GHRH together (but not alone) increased percentages of cells with leptin protein (41 ± 9%) or mRNA (57 ± 5%). Estrogen and GHRH also increased the percentages of AP cells that co-express leptin mRNA and GH antigens from 20 ± 2% of AP cells to 37 ± 5%. Although the significance of leptin in GH cells is not understood, it is clearly increased after stimulation with GHRH and estrogen. Because GH cells also have leptin receptors, this AP leptin may be an autocrine or paracrine regulator of pituitary cell function.
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Affiliation(s)
- Iris A McDuffie
- Department of Nutrition, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA
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Burwell RG, Clark EM, Dangerfield PH, Moulton A. Adolescent idiopathic scoliosis (AIS): a multifactorial cascade concept for pathogenesis and embryonic origin. SCOLIOSIS AND SPINAL DISORDERS 2016; 11:8. [PMID: 27252984 PMCID: PMC4888516 DOI: 10.1186/s13013-016-0063-1] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/08/2015] [Accepted: 01/04/2016] [Indexed: 02/01/2023]
Abstract
This paper formulates a novel multifactorial Cascade Concept for the pathogenesis of adolescent idiopathic scoliosis (AIS). This Concept stems from the longitudinal findings of Clark et al. (J Bone Miner Res 29(8):1729-36, 2014) who identified leptin body composition factors at 10 years of age associated with a scoliosis deformity found at 15 years. We interpret these findings in the light of some concepts for AIS pathogenesis. In particular, we speculate that the leptin body composition effect is linked to central nervous system development and the initiation of the asynchronous neuro-osseous growth mechanism that involves the creation of a neuraxis tether of relative anterior vertebral overgrowth. The latter mechanism in combination with age and gender-related anatomical variants of vertebral backward tilt (dorsal shear concept), human upright posture, adolescent growth factors, Hueter-Volkmann effect in vertebrae and vertebral bone mass abnormalities, lead to AIS, possibly both initiation and progression of scoliosis curvatures. Being multifactorial, while the Cascade Concept cannot be tested for all its components, some components should be testable by the method of numerical simulation. Clark et al. (J Bone Miner Res 29(8):1729-36, 2014) also suggested the origin of scoliosis was in the embryonic stages of life from cell types, including adipocytes and osteoblasts, derived from the same progenitor cells, and myoblasts from mesodermal somites. The involvement of cell types from different developmental origins suggests a process acting in embryonic life at a similar time, probably environmental, as previously proposed from anthropometric studies. As a Complex disease, AIS will involve genetic, environmental and life style factors operating in development and growth; this possibility needs evaluating in epidemiological studies.
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Affiliation(s)
- R Geoffrey Burwell
- Centre for Spinal Studies and Surgery, Queen's Medical Centre, Nottingham University Hospitals Trust, Nottingham, UK
| | - Emma M Clark
- Academic Rheumatology, Musculoskeletal Research Unit, University of Bristol, Bristol, UK
| | | | - Alan Moulton
- Department of Orthopaedic Surgery, King's Mill Hospital, Mansfield, UK
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20
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Hall ME, Harmancey R, Stec DE. Lean heart: Role of leptin in cardiac hypertrophy and metabolism. World J Cardiol 2015; 7:511-524. [PMID: 26413228 PMCID: PMC4577678 DOI: 10.4330/wjc.v7.i9.511] [Citation(s) in RCA: 69] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2015] [Revised: 06/16/2015] [Accepted: 07/23/2015] [Indexed: 02/06/2023] Open
Abstract
Leptin is an adipokine that has been linked with the cardiovascular complications resulting from obesity such as hypertension and heart disease. Obese patients have high levels of circulating leptin due to increased fat mass. Clinical and population studies have correlated high levels of circulating leptin with the development of cardiac hypertrophy in obesity. Leptin has also been demonstrated to increase the growth of cultured cardiomyocytes. However, several animal studies of obese leptin deficient mice have not supported a role for leptin in promoting cardiac hypertrophy so the role of leptin in this pathological process remains unclear. Leptin is also an important hormone in the regulation of cardiac metabolism where it supports oxidation of glucose and fatty acids. In addition, leptin plays a critical role in protecting the heart from excess lipid accumulation and the formation of toxic lipids in obesity a condition known as cardiac lipotoxicity. This paper focuses on the data supporting and refuting leptin’s role in promoting cardiac hypertrophy as well as its important role in the regulation of cardiac metabolism and protection against cardiac lipotoxicity.
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Abstract
Leptin is an adipose-derived cytokine that has an important role in bodyweight homeostasis and energy balance. There are a number of studies which have suggested that leptin and its receptors dysregulation play a critical role in the development of malignancies including hematological malignancies, mainly via activation of the JAK/STAT pathway which regulates downstream signaling pathways such as PI3K/AKT signaling and ERK1/2. In this review, current understandings of leptin/leptin receptors mediated pathogenesis in various lymphoid malignancies are described. Blocking of the leptin receptor might be a unique therapeutic approach for many hematological malignancies.
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Affiliation(s)
- Shahab Uddin
- a Translational Research Institute, Academic Health System, Hamad Medical Corporation , Doha , Qatar
| | - Ramzi M Mohammad
- a Translational Research Institute, Academic Health System, Hamad Medical Corporation , Doha , Qatar
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Wang C, Zhang H, Niu L, Guo J, Jia X, Wang L, Li L, Zhang H, Zhong T. The novel SNPs of leptin gene and their associations with growth traits in Chinese Nanjiang Yellow goat. Gene 2015; 572:35-41. [PMID: 26142105 DOI: 10.1016/j.gene.2015.06.073] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2014] [Revised: 06/08/2015] [Accepted: 06/27/2015] [Indexed: 01/09/2023]
Abstract
The leptin (LEP) gene encodes a protein that greatly affects the regulation of body weight, energy balance, and food intake in mammals. The objective of the present work was to identify genetic variants of the caprine LEP gene in 411 individuals from five Chinese goat breeds. Six novel single nucleotide polymorphisms (SNPs) (g.117T > C, g.1642G > A, g.2883G > A, g.3053T > C, g.3190G > A, and g.3314T > C) were detected using DNA sequencing. A chi-squared (χ(2)) test showed that all of the LEP SNPs were in Hardy-Weinberg equilibrium in the studied population (P > 0.05). Six common haplotypes were identified in the five goat populations, with frequencies ranging from 0.083 to 0.244. The r(2) linkage disequilibrium plot of the LEP SNPs indicated linkage disequilibrium only in the cultured breeds (NJ and JY). Statistical analysis revealed that all of the six SNPs of the LEP gene were associated with growth traits. The individuals with the GG genotype at g.1642G>A and g.3190G > A loci showed higher birth weight (2.38 ± 0.03, 2.43 ± 0.05) and weight at 2 months of age (10.59 ± 0.16, 10.71 ± 0.26) than the A-bearing genotypes (AA or GA, P < 0.05). Our findings indicate that polymorphisms of the caprine LEP gene might be important genetic factors influencing growth traits, and these genetic markers may be useful for future marker-assisted selection programs in goat breeding and production.
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Affiliation(s)
- Cen Wang
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, China
| | - Hao Zhang
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, China
| | - Lili Niu
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, China
| | - Jiazhong Guo
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, China
| | - Xianbo Jia
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, China
| | - Linjie Wang
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, China
| | - Li Li
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, China
| | - Hongping Zhang
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, China
| | - Tao Zhong
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, China.
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Briffa JF, McAinch AJ, Romano T, Wlodek ME, Hryciw DH. Leptin in pregnancy and development: a contributor to adulthood disease? Am J Physiol Endocrinol Metab 2015; 308:E335-50. [PMID: 25516549 DOI: 10.1152/ajpendo.00312.2014] [Citation(s) in RCA: 78] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Emerging research has highlighted the importance of leptin in fetal growth and development independent of its essential role in the maintenance of hunger and satiety through the modulation of neuropeptide Y and proopiomelanocortin neurons. Alterations in maternal-placental-fetal leptin exchange may modify the development of the fetus and contribute to the increased risk of developing disease in adulthood. In addition, leptin also plays an important role in reproductive functions, with plasma leptin concentrations rising in pregnant women, peaking during the third trimester. Elevated plasma leptin concentrations occur at the completion of organogenesis, and research in animal models has demonstrated that leptin is involved in the development and maturation of a number of organs, including the heart, brain, kidneys, and pancreas. Elevated maternal plasma leptin is associated with maternal obesity, and reduced fetal plasma leptin is correlated with intrauterine growth restriction. Alterations in plasma leptin during development may be associated with an increased risk of developing a number of adulthood diseases, including cardiovascular, metabolic, and renal diseases via altered fetal development and organogenesis. Importantly, research has shown that leptin antagonism after birth significantly reduces maturation of numerous organs. Conversely, restoration of the leptin deficiency after birth in growth-restricted animals restores the offspring's body weight and improves organogenesis. Therefore, leptin appears to play a major role in organogenesis, which may adversely affect the risk of developing a number of diseases in adulthood. Therefore, greater understanding of the role of leptin during development may assist in the prevention and treatment of a number of disease states that occur in adulthood.
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Affiliation(s)
- Jessica F Briffa
- Department of Physiology, University of Melbourne, Parkville, Australia
| | - Andrew J McAinch
- Centre for Chronic Disease Prevention and Management, College of Health and Biomedicine, Victoria University, St. Albans, Australia; and
| | - Tania Romano
- Department of Human Biosciences, Latrobe University, Bundoora, Australia
| | - Mary E Wlodek
- Department of Physiology, University of Melbourne, Parkville, Australia
| | - Deanne H Hryciw
- Department of Physiology, University of Melbourne, Parkville, Australia;
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24
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Uddin S, Hussain AR, Khan OS, Al-Kuraya KS. Role of dysregulated expression of leptin and leptin receptors in colorectal carcinogenesis. Tumour Biol 2014; 35:871-879. [PMID: 24014051 DOI: 10.1007/s13277-013-1166-4] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2013] [Accepted: 08/29/2013] [Indexed: 12/13/2022] Open
Abstract
Leptin is a multifunctional adipose-derived cytokine that plays a critical role in bodyweight homeostasis and energy balance. Plasma level of leptin is an indicator of the amount of energy stored in adipose tissues. Recently, leptin and leptin receptor dysregulation have been reported in a variety of malignant cells including colorectal cancers (CRCs). There are growing evidence that leptin may be the link between obesity and CRC carcinogenesis. Leptin influence the growth and proliferation of cancer cells via activation of various growth and survival signaling pathways including JAK/STAT, PI3-kinase/AKT, and/or MAP kinases. In this review, current understanding of leptin and its receptor's roles in the pathogenesis of colonogenic cancer has been described.
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Affiliation(s)
- Shahab Uddin
- Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Center, MBC#98-16, P.O. Box 3354, Riyadh, 11211, Saudi Arabia,
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25
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Chen J, Mo H, Guo R, You Q, Huang R, Wu K. Inhibition of the leptin-induced activation of the p38 MAPK pathway contributes to the protective effects of naringin against high glucose-induced injury in H9c2 cardiac cells. Int J Mol Med 2014; 33:605-12. [PMID: 24399619 DOI: 10.3892/ijmm.2014.1614] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2013] [Accepted: 12/24/2013] [Indexed: 11/05/2022] Open
Abstract
Leptin, a product of the obese gene, has been reported to contribute to the development of cardiomyocyte hypertrophy in patients with diabetes and to activate the p38 mitogen-activated protein kinase (MAPK) pathway in cardiomyocytes. In this study, we demonstrate that naringin, a citrus flavonone, protects cardiomyoblasts (H9c2 cells) against high glucose (HG)-induced apoptosis by modulating the activation of the p38 MAPK pathway. We investigated the hypothesis that naringin prevents HG-induced injury by inhibiting the leptin-induced activation of the p38 MAPK pathway in H9c2 cells. Our results demonstrated that the exposure of H9c2 cells to HG (35 mmol/l) for a 24 h markedly upregulated the expression levels of both leptin and leptin receptors. However, the increase in the expression levels of leptin and leptin receptors was greatly attenuated by treatment of the H9c2 cells with 80 µmol/l naringin 2 h prior to exposure to HG. In addition, treatment of the cells with 50 ng/ml leptin antagonist (LA) for 24 h prior to exposure to HG markedly ameliorated the increased expression of phosphorylated (p)-p38 MAPK induced by HG. Of note, pre-treatment of the cells with either 80 µmol/l naringin or 50 ng/ml LA markedly inhibited the HG-induced injury, leading to an increase in cell viability and a decrease in the total number of apoptotic cells, preventing reactive oxygen species (ROS) generation, as well as the dissipation of mitochondrial membrane potential (MMP). In conclusion, the findings of the present study provide the first evidence that the leptin-induced activation of the p38 MAPK pathway is involved in HG-induced injury, including cytotoxicity, apoptosis, ROS generation and the dissipation of MMP in H9c2 cardiac cells. Our data demonstrate that naringin protects cardiac cells against HG-induced injury by inhibiting the leptin-induced activation of the p38 MAPK pathway.
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Affiliation(s)
- Jingfu Chen
- Department of Cardiovasology, The Affiliated Hospital, Guangdong Medical College, Zhanjiang, Guangdong 524001, P.R. China
| | - Hailiang Mo
- Department of Cardiovasology, The Affiliated Hospital, Guangdong Medical College, Zhanjiang, Guangdong 524001, P.R. China
| | - Runmin Guo
- Department of Cardiovasology, The Affiliated Hospital, Guangdong Medical College, Zhanjiang, Guangdong 524001, P.R. China
| | - Qiong You
- Department of Cardiovasology, The Affiliated Hospital, Guangdong Medical College, Zhanjiang, Guangdong 524001, P.R. China
| | - Ruina Huang
- Department of Cardiovasology, The Affiliated Hospital, Guangdong Medical College, Zhanjiang, Guangdong 524001, P.R. China
| | - Keng Wu
- Department of Cardiovasology, The Affiliated Hospital, Guangdong Medical College, Zhanjiang, Guangdong 524001, P.R. China
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26
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Will K, Kuzinski J, Kalbe C, Palin MF, Rehfeldt C. Effects of leptin and adiponectin on the growth of porcine myoblasts are associated with changes in p44/42 MAPK signaling. Domest Anim Endocrinol 2013; 45:196-205. [PMID: 24209504 DOI: 10.1016/j.domaniend.2013.09.002] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2013] [Revised: 09/13/2013] [Accepted: 09/13/2013] [Indexed: 12/15/2022]
Abstract
We hypothesized that both adiponectin and leptin affect the growth of porcine skeletal muscle cells, with fatty acids acting as modifiers in adipokine action and that both adipokines influence the gene expression of their receptors. Therefore, the objective of this study was to investigate the effects of recombinant adiponectin and leptin on cell number (DNA) and DNA synthesis rate with and without oleic acid supplementation, on cell death, and on key intracellular signaling molecules of proliferating porcine myoblasts in vitro. Moreover, the mRNA expression of genes encoding for the leptin and adiponectin receptors (LEPR, ADIPOR1, ADIPOR2) as affected by leptin or adiponectin was examined. Recombinant porcine adiponectin (40 μg/mL) and leptin (20 ng/mL) increased DNA synthesis rate, measured as [(3)H]-thymidine incorporation (P < 0.01), reduced cell viability in terms of lactate dehydrogenase release (P < 0.05), or lowered DNA content after 24 h (P < 0.05). In adiponectin-treated cultures, oleic acid supplementation increased DNA synthesis rate and reduced cell number in a dose-dependent manner (P < 0.05). Both adiponectin (P = 0.07) and leptin (P < 0.05) induced a transient activation of p44/42 mitogen-activated protein kinase (MAPK) after 15 min, followed by decreases after 60 and 180 min (P < 0.05). Adiponectin tended to increase c-fos activation (P = 0.08) and decreased p53 activation at 180 min (P = 0.03). Both adiponectin and leptin down-regulated the abundance of ADIPOR2 mRNA and, transiently, of LEPR mRNA (P < 0.05). In conclusion, adiponectin and leptin may adversely affect the growth of porcine myoblasts, which is related to p44/42 MAPK signaling and associated with changes in ligand receptor gene expression.
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Affiliation(s)
- K Will
- Institute for Muscle Biology and Growth, Leibniz Institute for Farm Animal Biology (FBN), Wilhelm-Stahl-Allee 2, 18196 Dummerstorf, Germany
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27
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Dall'Aglio C, Mercati F, Pascucci L, Ceccarelli P. Immunolocalization of leptin and its receptor in the pancreas of the horse. Acta Histochem 2013; 115:757-60. [PMID: 23830247 DOI: 10.1016/j.acthis.2013.05.008] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2012] [Revised: 05/17/2013] [Accepted: 05/20/2013] [Indexed: 11/29/2022]
Abstract
The aim of the present study was to demonstrate the presence and the distribution of leptin and its receptor in the pancreas of horses of both sexes by immunohistochemical techniques. The presence and the distribution of leptin receptor were also investigated in the initial portion of the duodenum, near the duodenal ampulla. The immunohistochemical investigation demonstrates the immunolocalization of both leptin and its receptor in the endocrine cells of pancreatic islets, which led us to hypothesize that leptin may possibly exert an autocrine/paracrine action on the endocrine pancreas. Examination of the exocrine pancreas in the same treated sections showed the presence of leptin-positive cells in the wall of the interlobular ducts where, however, the receptor was not found. This observation led us to consider that some cells of the ducts may perform some minimal secretory activity, and that leptin produced by these ductal cells may reach the duodenum in the pancreatic juice. This hypothesis is enhanced by the presence of leptin-receptor in the duodenum of the same animals, where the epithelial cells of the mucosa showed intense immunolocalization in the brush border. Consequently it is possible that the ductular leptin may play a regulatory role on the functionality of the enterocytes.
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Affiliation(s)
- Cecilia Dall'Aglio
- Dipartimento di Scienze Biopatologiche Veterinarie ed Igiene delle Produzioni Animali e Alimentari, Sezione di Anatomia - Università degli Studi di Perugia, Via San Costanzo 4, 06126 Perugia, Italy.
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28
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Vizuete G, Diez E, Galisteo J, Agüera E, Aguilera-Tejero E, Perez-Marín CC. Comparison of different treatments for oestrous induction in seasonally anovulatory mares. Reprod Domest Anim 2012; 48:463-9. [PMID: 23137389 DOI: 10.1111/rda.12098] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2012] [Accepted: 09/12/2012] [Indexed: 11/28/2022]
Abstract
The aim of this study was to evaluate the effects of different treatments for induction and synchronization of oestrus and ovulation in seasonally anovulatory mares. Fifteen mares formed the control group (C), while 26 mares were randomly assigned to three treatment groups. Group T1 (n = 11) were treated with oral altrenogest (0.044 mg/kg; Regumate(®) ) during 11 days. Group T2 (n = 7) was intravaginally treated with 1.38 g of progesterone (CIDR(®) ) for 11 days. In group T3 (n = 8), mares were also treated with CIDR(®) , but only for 8 days. All mares received PGF2α 1 day after finishing the treatment. Sonographic evaluation of follicles, pre-ovulatory follicle size and ovulation time was recorded. Progesterone and leptin levels were analysed. Results show that pre-ovulatory follicles were developed after the treatment in 88.5% of mares. However, the pre-ovulatory follicle growth was dispersal, and sometimes it was detected when treatment was not finished. While in mares treated with intravaginal device, the follicle was soon detected (1.5 ± 1.2 days and 2.3 ± 2.0 days in T2 and T3 groups, respectively), in T1 group, the pre-ovulatory follicle was detected slightly later (3.9 ± 1.6 days). The interval from the end of treatment to ovulation did not show significant differences between groups (T1 = 13.1 ± 2.5 days; T2 = 11.0 ± 3.6 days; T3 = 13.8 ± 4.3 days). The pregnancy rate was 47.4%, similar to the rate observed in group C (46.7%; p > 0.05). Initial leptin concentrations were significantly higher in mares, which restart their ovarian activity after treatments, suggesting a role in the reproduction mechanisms in mares. It could be concluded that the used treatments may be effective for oestrous induction in mares during the late phase of the seasonally anovulatory period. Furthermore, they cannot synchronize oestrus, and then, it is necessary to know the reproductive status of mares when these treatments are used for oestrous synchronization.
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Affiliation(s)
- G Vizuete
- Department of Animal Medicine and Surgery, Faculty of Veterinary Medicine, University of Cordoba, Cordoba, Spain
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29
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Siawrys G, Smolinska N. Direct in vitro effect of LH and steroids on leptin gene expression and leptin secretion by porcine luteal cells during the mid-luteal phase of the estrous cycle. Reprod Biol 2012; 12:317-23. [DOI: 10.1016/j.repbio.2012.10.003] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2012] [Accepted: 05/20/2012] [Indexed: 10/27/2022]
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30
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Akhter N, Odle AK, Allensworth-James ML, Haney AC, Syed MM, Cozart MA, Chua S, Kineman R, Childs GV. Ablation of leptin signaling to somatotropes: changes in metabolic factors that cause obesity. Endocrinology 2012; 153:4705-15. [PMID: 22865370 PMCID: PMC3512011 DOI: 10.1210/en.2012-1331] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2012] [Accepted: 07/12/2012] [Indexed: 01/22/2023]
Abstract
Mice with somatotrope-specific deletion of the Janus kinase binding site in leptin receptors are GH deficient as young adults and become obese by 6 months of age. This study focused on the metabolic status of young (3-4.5 month old) preobese mutant mice. These mutants had normal body weights, lean body mass, serum leptin, glucose, and triglycerides. Mutant males and females showed significantly higher respiratory quotients (RQ) and lower energy output, resulting from a higher volume of CO(2) output and lower volume of O(2) consumption. Deletion mutant females were significantly less active than controls; they had higher levels of total serum ghrelin and ate more food. Mutant females also had lower serum insulin and higher glucagon. In contrast, deletion mutant males were not hyperphagic, but they were more active and spent less time sleeping. Adiponectin and resistin, both products of adipocytes, were increased in male and female mutant mice. In addition, mutant males showed an increase in circulating levels of the potent lipogenic hormone, glucose-dependent insulinotropic peptide. Taken together, these results indicate that mutant mice may become obese due to a reduction in lipid oxidation and energy expenditure. This may stem from GH deficiency. Reduced fat oxidation and enhanced insulin sensitivity (in females) are directly related to GH deficiency in mutant mice because GH has been shown by others to increase insulin sensitivity and fat oxidation and reduce carbohydrate oxidation. Gender-dependent alterations in metabolic signals may further exacerbate the future obese phenotype and affect the timing of its onset. Females show a delay in onset of obesity, perhaps because of their low serum insulin, which is lipogenic, whereas young males already have higher levels of the lipogenic hormone, glucose-dependent insulinotropic peptide. These findings signify that leptin signals to somatotropes are vital for the normal metabolic activity needed to optimize body composition.
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Affiliation(s)
- Noor Akhter
- Department of Neurobiology and Developmental Sciences, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA
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Abstract
Fat affects meat quality, value and production efficiency as well as providing energy reserves for pregnancy and lactation in farm livestock. Leptin, the adipocyte product of the obese (ob) gene, was quickly seen as a predictor of body fat content in animals approaching slaughter and an aid to assessing reproductive readiness in females. Its participation in inflammation and immune responses that help animals survive infection and trauma has clear additional relevance to meat and milk production. Furthermore, almost a decade of discoveries of nucleotide polymorphisms in the leptin and leptin receptor genes has suggested useful applications relating to feed intake regulation, the efficiency of feed use, the composition of growth, the timing of puberty, mammogenesis and mammary gland function and fertility in cattle, pigs and poultry. The current review attempts to summarise where research has taken us in each of these aspects and speculates on where future research might lead.
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32
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Effects of leptin and adiponectin on proliferation and protein metabolism of porcine myoblasts. Histochem Cell Biol 2012; 138:271-87. [DOI: 10.1007/s00418-012-0949-9] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/26/2012] [Indexed: 02/01/2023]
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Tyra M, Ropka-Molik K, Eckert R, Piórkowska K, Oczkowicz M. H-FABP and LEPR gene expression profile in skeletal muscles and liver during ontogenesis in various breeds of pigs. Domest Anim Endocrinol 2011; 40:147-54. [PMID: 21194874 DOI: 10.1016/j.domaniend.2010.10.001] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2010] [Revised: 10/26/2010] [Accepted: 10/27/2010] [Indexed: 10/18/2022]
Abstract
The genes coding for H-FABP (heart acid-binding protein) and LEPR (leptin receptor) are considered to be candidates for lipid metabolism and thus affect fat deposition in pigs. The aim of our study was to assess the amount of H-FABP and LEPR transcript in the skeletal muscles (m. longissimus dorsi, m. semimembranosus) and liver of pigs of various ages. The experiments were carried out on 5 popular breeds of swine raised in Poland which exhibit different levels of fat tissue. Furthermore, we examined the effect of H-FABP and LEPR genotypes (HinfI, HpaII, and HaeIII for H-FABP and HpaII for LEPR) on the expression abundance of these genes. We confirmed a statistically significant relationship between the breed (P<.001), type of tissue (LEPR P<.001; H-FABP P<.01), and age of the animal (P<.05) on the abundance of mRNA transcript of both genes. In all breeds, the expression of the leptin receptor gene increased significantly (P<.01) with age in muscle tissue, whereas this relationship was not observed in liver tissue. However, the expression of the H-FABP gene in muscles did not change with age or breed, although in the liver expression levels were high in young (60 and 90 d) pigs. In conclusion, H-FABP and LEPR genes are strongly related to the development and function of fat tissue in pigs.
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Affiliation(s)
- M Tyra
- Department of Animal Genetics and Breeding, National Research Institute of Animal Production, Balice, Poland
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Tian Y, Wang S, Ma Y, Lim G, Kim H, Mao J. Leptin enhances NMDA-induced spinal excitation in rats: A functional link between adipocytokine and neuropathic pain. Pain 2011; 152:1263-1271. [PMID: 21376468 DOI: 10.1016/j.pain.2011.01.054] [Citation(s) in RCA: 63] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2010] [Revised: 01/18/2011] [Accepted: 01/27/2011] [Indexed: 11/18/2022]
Abstract
Recent studies have shown that leptin (an adipocytokine) played an important role in nociceptive behavior induced by nerve injury, but the cellular mechanism of this action remains unclear. Using the whole-cell patch-clamp recording from rat's spinal cord slices, we showed that superfusion of leptin onto spinal cord slices dose-dependently enhanced N-methyl-d-aspartate (NMDA) receptor-mediated currents in spinal cord lamina II neurons. At the cellular level, the effect of leptin on spinal NMDA-induced currents was mediated through the leptin receptor and the JAK2/STAT3 (but not PI3K or MAPK) pathway, as the leptin effect was abolished in leptin receptor-deficient (db/db) mice and inhibited by a JAK/STAT inhibitor. Moreover, we demonstrated in naïve rats that a single intrathecal administration of leptin enhanced spontaneous biting, scratching, and licking behavior induced by intrathecal NMDA and that repeated intrathecal administration of leptin elicited thermal hyperalgesia and mechanical allodynia, which was attenuated by the noncompetitive NMDA receptor antagonist MK-801. Intrathecal leptin also upregulated the expression of NMDA receptors and pSTAT3 within the rat's spinal cord dorsal horn, and intrathecal MK-801 attenuated this leptin effect as well. Our data demonstrate a relationship between leptin and NMDA receptor-mediated spinal neuronal excitation and its functional role in nociceptive behavior. Since leptin contributes to nociceptive behavior induced by nerve injury, the present findings suggest an important cellular link between the leptin's spinal effect and the NMDA receptor-mediated cellular mechanism of neuropathic pain. A functional link is demonstrated between leptin, an adipocytokine, and the cellular mechanisms of neuropathic pain via enhancement of function and expression of spinal N-methyl-d-aspartate receptors.
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Affiliation(s)
- Yinghong Tian
- MGH Center for Translational Pain Research, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA Department of Physiology, Southern Medical University, Guangzhou 510515, China
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35
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Childs GV, Akhter N, Haney A, Syed M, Odle A, Cozart M, Brodrick Z, Gaddy D, Suva LJ, Akel N, Crane C, Benes H, Charlesworth A, Luque R, Chua S, Kineman RD. The somatotrope as a metabolic sensor: deletion of leptin receptors causes obesity. Endocrinology 2011; 152:69-81. [PMID: 21084451 PMCID: PMC3033057 DOI: 10.1210/en.2010-0498] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2010] [Accepted: 10/07/2010] [Indexed: 01/01/2023]
Abstract
Leptin, the product of the Lep gene, reports levels of adiposity to the hypothalamus and other regulatory cells, including pituitary somatotropes, which secrete GH. Leptin deficiency is associated with a decline in somatotrope numbers and function, suggesting that leptin may be important in their maintenance. This hypothesis was tested in a new animal model in which exon 17 of the leptin receptor (Lepr) protein was selectively deleted in somatotropes by Cre-loxP technology. Organ genotyping confirmed the recombination of the floxed LepR allele only in the pituitary. Deletion mutant mice showed a 72% reduction in pituitary cells bearing leptin receptor (LEPR)-b, a 43% reduction in LEPR proteins and a 60% reduction in percentages of immunopositive GH cells, which correlated with reduced serum GH. In mutants, LEPR expression by other pituitary cells was like that of normal animals. Leptin stimulated phosphorylated Signal transducer and activator of transcription 3 expression in somatotropes from normal animals but not from mutants. Pituitary weights, cell numbers, IGF-I, and the timing of puberty were not different from control values. Growth curves were normal during the first 3 months. Deletion mutant mice became approximately 30-46% heavier than controls with age, which was attributed to an increase in fat mass. Serum leptin levels were either normal in younger animals or reflected the level of obesity in older animals. The specific ablation of the Lepr exon 17 gene in somatotropes resulted in GH deficiency with a consequential reduction in lipolytic activity normally maintained by GH and increased adiposity.
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Affiliation(s)
- Gwen V Childs
- Professor and Chair, Department of Neurobiology and Developmental Sciences, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA.
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36
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Malli F, Papaioannou AI, Gourgoulianis KI, Daniil Z. The role of leptin in the respiratory system: an overview. Respir Res 2010; 11:152. [PMID: 21040518 PMCID: PMC2988727 DOI: 10.1186/1465-9921-11-152] [Citation(s) in RCA: 92] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2010] [Accepted: 10/31/2010] [Indexed: 12/13/2022] Open
Abstract
Since its cloning in 1994, leptin has emerged in the literature as a pleiotropic hormone whose actions extend from immune system homeostasis to reproduction and angiogenesis. Recent investigations have identified the lung as a leptin responsive and producing organ, while extensive research has been published concerning the role of leptin in the respiratory system. Animal studies have provided evidence indicating that leptin is a stimulant of ventilation, whereas researchers have proposed an important role for leptin in lung maturation and development. Studies further suggest a significant impact of leptin on specific respiratory diseases, including obstructive sleep apnoea-hypopnoea syndrome, asthma, COPD and lung cancer. However, as new investigations are under way, the picture is becoming more complex. The scope of this review is to decode the existing data concerning the actions of leptin in the lung and provide a detailed description of leptin's involvement in the most common disorders of the respiratory system.
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Affiliation(s)
- Foteini Malli
- Respiratory Medicine Department, University of Thessaly School of Medicine, University Hospital of Larissa, 41110, Greece
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Wu Y, Luo H, Liu J, Kang D, McNeilly AS, Cui S. LIM homeodomain transcription factor Isl-1 enhances follicle stimulating hormone-beta and luteinizing hormone-beta gene expression and mediates the activation of leptin on gonadotropin synthesis. Endocrinology 2010; 151:4787-800. [PMID: 20702576 DOI: 10.1210/en.2010-0208] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
The Lin-11, Isl-1, and Mec-3 (LIM) homeodomain transcription factor Isl-1 has been reported to be involved in pituitary development in the early stages of mouse embryogenesis. Our recent studies have shown that Isl-1 is mainly located in the pituitary gonadotropes throughout pituitary development and persists to adulthood. We still do not know the physiological functions of Isl-1 expression and its related mechanisms in the pituitary gland. The aim of the present study was to examine the hypothesis that Isl-1 is involved in regulating pituitary gonadotropin hormone (FSH/LH) production by activating FSHβ and LHβ gene expressions. We have shown that Isl-1 activates FSHβ and LHβ subunit promoters and endogenous gene transcription in LβT2 cells. In addition, Isl-1 overexpression significantly increased FSH synthesis and secretion but not LH. The actions of Isl-1 were not observed when the homeodomain or LIM1 domains are mutated. This demonstrates that Isl-1 induction of FSHβ and LHβ is by both direct and indirect binding of Isl-1 to DNA sequences. Furthermore, Isl-1 expressional level was up-regulated in LβT2 cells after exposure to GnRH, activin, and leptin. However, RNA interference-induced knockdown of Isl-1 significantly reduced the effect of leptin but did not obviously influence the stimulating effects of GnRH and activin on LH and FSH production. In conclusion, the results demonstrate that the LIM-homeodomain transcription factor Isl-1 functions to increase FSHβ/LHβ gene transcription, and mediates the effects of leptin on gonadotropin synthesis.
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Affiliation(s)
- Yingjie Wu
- State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing 100193, People's Republic of China
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Gioacchini G, Maradonna F, Lombardo F, Bizzaro D, Olivotto I, Carnevali O. Increase of fecundity by probiotic administration in zebrafish (Danio rerio). Reproduction 2010; 140:953-9. [PMID: 20833753 DOI: 10.1530/rep-10-0145] [Citation(s) in RCA: 52] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
It is well known established that reproduction is sensitive to the state of energy reserves, and that there is a balance between energy homeostasis and fertility. In this view, this study examined the effects of the probiotic Lactobacillus rhamnosus, as a feed additive, on zebrafish (Danio rerio) fecundity. Ten days of probiotic treatment modulate the gene expression of neuropeptide hormones and metabolic signals, such as kiss1, kiss2 and leptin both at the CNS level and at the peripheral level. The increase in fecundity brought about by the probiotic was demonstrated by the higher number of ovulated eggs in vivo and by the higher germinal vesicle breakdown rate obtained with the in vitro maturation assay. The increase in oocyte maturation was associated with increased transcription of genes coding for signals which induce the maturation phase, such as lhcgr, cbr1l, and paqr8 genes, concomitant with a decreased transcription of genes coding for local factors which prevent oocyte maturation, such as tgfb1, gdf9, and bmp15. In conclusion, all these findings highlight the action of L. rhamnosus both on the endocrine system and at the local level by inducing oocyte maturation. The significance of the results herein obtained underlined the importance of diet in the reproductive process, supporting the hypothesis that feed additives can improve fecundity. Considering that the zebrafish has been clearly established as a vertebrate model for biomedical research, these results support the potentiality of feed additives such as probiotics, frequently used in the human diet, as a new technology to improve reproduction in all vertebrates, including humans.
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Affiliation(s)
- Giorgia Gioacchini
- Department of Marine Sciences, Polytechnic University of Marche, via Brecce Bianche, 60131 Ancona, Italy
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Banerjee A, Meenakumari KJ, Krishna A. Role of leptin in delayed embryonic development in the Indian short-nosed fruit bat, Cynopterus sphinx. Gen Comp Endocrinol 2010; 168:36-45. [PMID: 20399211 DOI: 10.1016/j.ygcen.2010.04.002] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2009] [Revised: 03/29/2010] [Accepted: 04/12/2010] [Indexed: 11/27/2022]
Abstract
An adiposity-associated rise in leptin occurs at the time of delayed embryonic development in Cynopterus sphinx. The aim of present study was to examine the mechanism by which leptin may inhibit progesterone, and therefore could be responsible for delayed development. The study showed a significant increase in circulating leptin level during the period of increased fat accumulation, which coincided with significant decrease in serum progesterone level and delayed embryonic development in C. sphinx. The study showed increased Ob-R expression in the corpus luteum and in the utero-embryonic unit during the period of delayed embryonic development. The in vitro study showed suppressive effect of leptin on progesterone synthesis. The effect of high dose of leptin on ovarian steroidogenesis was found to be mediated through decreased expression of StAR and LH-R proteins in the ovary. The treatment with leptin caused increased expression of STAT 3 and iNOS proteins in the ovary, which correlated with decreased expression of StAR protein in the ovary. The inhibitory effects of leptin on progesterone synthesis in the ovary are thus mediated through STAT 3 and iNOS-NO signaling pathways. This study further demonstrated low expression of PCNA coinciding with the increased concentration of the leptin receptor in the utero-embryonic unit and high circulating leptin level during November. In conclusion, adiposity associated increased leptin level during November-December might play role in suppressing progesterone synthesis in the corpus luteum as well as suppressing the rate of cell-proliferation in the utero-embryonic unit thereby causing delayed embryonic development in C. sphinx.
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Affiliation(s)
- A Banerjee
- Department of Zoology, Banaras Hindu University, Varanasi, UP 221 005, India
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40
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Kalbe C, Puppe B. Long-term cognitive enrichment affects opioid receptor expression in the amygdala of domestic pigs. GENES BRAIN AND BEHAVIOR 2010; 9:75-83. [DOI: 10.1111/j.1601-183x.2009.00536.x] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
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41
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IGF-I mediated inhibition of leptin receptor expression in porcine hepatocytes. Comp Biochem Physiol B Biochem Mol Biol 2010; 155:43-8. [DOI: 10.1016/j.cbpb.2009.09.007] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2008] [Revised: 09/18/2009] [Accepted: 09/21/2009] [Indexed: 11/21/2022]
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Siawrys G, Kaminski T, Smolinska N, Przala J. Expression of Leptin and Long-form Leptin-receptor Proteins in Porcine Hypothalamus during Oestrous Cycle and Pregnancy. Reprod Domest Anim 2009; 44:920-6. [DOI: 10.1111/j.1439-0531.2008.01118.x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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Smolinska N, Kaminski T, Siawrys G, Przala J. Leptin gene and protein expression in the ovary during the oestrous cycle and early pregnancy in pigs. Reprod Domest Anim 2009; 45:e174-83. [PMID: 19930136 DOI: 10.1111/j.1439-0531.2009.01542.x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
Leptin, the product of the obese gene, is the hormone originally identified in adipocytes. It is involved in the control of satiety and energy metabolism. More recent observations suggest that leptin plays an important role in reproduction. Leptin mRNA and protein have been found in the human and the murine ovary. However, the expression of leptin in the porcine ovary has not been examined. Therefore, the aim of the present work was to compare the expression levels of porcine leptin mRNA by semiquantitative RT-PCR and in situ hybridization, as well as leptin protein by Western blotting in the corpus luteum (CL) and ovarian stroma (OS) during mid- and late-luteal phase of the oestrous cycle as well as during days 14-16 and 30-32 of pregnancy. Leptin gene and protein expression in CL was increased on days 14-16 of the cycle compared with pregnant animals. Leptin gene expression in OS was higher during the late-luteal phase of the cycle than on days 30-32 after conception. However, comparison of leptin protein expression in OS between days 14-16 of the cycle and days 30-32 of pregnancy indicates a higher protein expression during pregnancy. Moreover, leptin gene expression was higher in porcine CL and OS on days 14-16 of pregnancy in comparison to days 30-32. Contrary to leptin mRNA expression, a higher leptin protein expression was observed on days 30-32 compared with days 14-16 after conception. In summary, the present study provides the first evidence that leptin mRNA and protein occur in porcine ovary and vary during the oestrous cycle and pregnancy. Moreover, the obtained results indicate that also locally synthesized leptin may participate in the control of pig reproduction by exercising its action at the ovarian level.
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Affiliation(s)
- N Smolinska
- Department of Animal Physiology, University of Warmia and Mazury in Olsztyn, Olsztyn, Poland
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Burwell RG, Aujla RK, Grevitt MP, Dangerfield PH, Moulton A, Randell TL, Anderson SI. Pathogenesis of adolescent idiopathic scoliosis in girls - a double neuro-osseous theory involving disharmony between two nervous systems, somatic and autonomic expressed in the spine and trunk: possible dependency on sympathetic nervous system and hormones with implications for medical therapy. SCOLIOSIS 2009; 4:24. [PMID: 19878575 PMCID: PMC2781798 DOI: 10.1186/1748-7161-4-24] [Citation(s) in RCA: 80] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/11/2009] [Accepted: 10/31/2009] [Indexed: 12/24/2022]
Abstract
Anthropometric data from three groups of adolescent girls - preoperative adolescent idiopathic scoliosis (AIS), screened for scoliosis and normals were analysed by comparing skeletal data between higher and lower body mass index subsets. Unexpected findings for each of skeletal maturation, asymmetries and overgrowth are not explained by prevailing theories of AIS pathogenesis. A speculative pathogenetic theory for girls is formulated after surveying evidence including: (1) the thoracospinal concept for right thoracic AIS in girls; (2) the new neuroskeletal biology relating the sympathetic nervous system to bone formation/resorption and bone growth; (3) white adipose tissue storing triglycerides and the adiposity hormone leptin which functions as satiety hormone and sentinel of energy balance to the hypothalamus for long-term adiposity; and (4) central leptin resistance in obesity and possibly in healthy females. The new theory states that AIS in girls results from developmental disharmony expressed in spine and trunk between autonomic and somatic nervous systems. The autonomic component of this double neuro-osseous theory for AIS pathogenesis in girls involves selectively increased sensitivity of the hypothalamus to circulating leptin (genetically-determined up-regulation possibly involving inhibitory or sensitizing intracellular molecules, such as SOC3, PTP-1B and SH2B1 respectively), with asymmetry as an adverse response (hormesis); this asymmetry is routed bilaterally via the sympathetic nervous system to the growing axial skeleton where it may initiate the scoliosis deformity (leptin-hypothalamic-sympathetic nervous system concept = LHS concept). In some younger preoperative AIS girls, the hypothalamic up-regulation to circulating leptin also involves the somatotropic (growth hormone/IGF) axis which exaggerates the sympathetically-induced asymmetric skeletal effects and contributes to curve progression, a concept with therapeutic implications. In the somatic nervous system, dysfunction of a postural mechanism involving the CNS body schema fails to control, or may induce, the spinal deformity of AIS in girls (escalator concept). Biomechanical factors affecting ribs and/or vertebrae and spinal cord during growth may localize AIS to the thoracic spine and contribute to sagittal spinal shape alterations. The developmental disharmony in spine and trunk is compounded by any osteopenia, biomechanical spinal growth modulation, disc degeneration and platelet calmodulin dysfunction. Methods for testing the theory are outlined. Implications are discussed for neuroendocrine dysfunctions, osteopontin, sympathoactivation, medical therapy, Rett and Prader-Willi syndromes, infantile idiopathic scoliosis, and human evolution. AIS pathogenesis in girls is predicated on two putative normal mechanisms involved in trunk growth, each acquired in evolution and unique to humans.
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Affiliation(s)
- R Geoffrey Burwell
- Centre for Spinal Studies and Surgery, Nottingham University Hospitals Trust, Queen's Medical Centre Campus, Nottingham, UK
| | - Ranjit K Aujla
- Centre for Spinal Studies and Surgery, Nottingham University Hospitals Trust, Queen's Medical Centre Campus, Nottingham, UK
| | - Michael P Grevitt
- Centre for Spinal Studies and Surgery, Nottingham University Hospitals Trust, Queen's Medical Centre Campus, Nottingham, UK
| | | | - Alan Moulton
- Department of Orthopaedic Surgery, King's Mill Hospital, Mansfield, UK
| | - Tabitha L Randell
- Department of Child Health, Nottingham University Hospitals Trust, Queen's Medical Centre Campus, Nottingham, UK
| | - Susan I Anderson
- School of Biomedical Sciences, University of Nottingham, Nottingham, UK
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Di Giancamillo A, Rossi R, Vitari F, Pastorelli G, Corino C, Domeneghini C. Dietary conjugated linoleic acids decrease leptin in porcine adipose tissue. J Nutr 2009; 139:1867-72. [PMID: 19710164 DOI: 10.3945/jn.109.110627] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Abstract
We investigated the effects of dietary conjugated linoleic acids (CLA) on white adipose tissue (WAT) in heavy pigs. Twelve pigs were assigned to 1 of 2 groups supplemented with either 0 or 0.75% of a CLA preparation (isomeric mixture) and were slaughtered at 159 +/- 2.3 kg live weight. Their subcutaneous WAT was analyzed by both chemical and microanatomical methods. The WAT of CLA-fed pigs tended to have a higher protein content (P = 0.064) and smaller adipocytes (P = 0.053) than that of control (CTR) pigs. The number of proliferating preadipocytes tended to be greater (P = 0.076) in pigs fed CLA, whereas the number of apoptotic adipocytes was greater (P < 0.01) than in CTR pig. Immunohistochemistry revealed that leptin (Ob) expression was lower (P = 0.048) in adipocytes from treated pigs and Western blot quantification of Ob revealed lower levels (P < 0.05) in CLA-fed pigs. The Ob receptor was not affected by dietary CLA supplementation. Tyrosine hydroxylase activity was higher (P < 0.001) in WAT of CLA fed-pigs than in CTR. It is conceivable that the increased noradrenergic activity due to dietary CLA decreases the Ob expression, although it does not diminish the lipid content of WAT, at least in heavy pigs. This article describes the interaction between CLA and Ob in the WAT of heavy pigs and we hypothesize that there is an increased noradrenergic stimulation of lipolysis directly in the target tissue.
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Affiliation(s)
- Alessia Di Giancamillo
- Department of Veterinary Sciences and Technologies for Food Safety, University of Milan, 20133 Milan, Italy
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Leptin in sow: Influence on the resumption of cycle activity after weaning and on the piglet gain. Livest Sci 2009. [DOI: 10.1016/j.livsci.2009.01.005] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
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El-Maaty AMA, Gabr FI. Relation between leptin and estradiol levels in Egyptian lactating Arab mares during foaling heat. Anim Reprod Sci 2009; 117:95-8. [PMID: 19577385 DOI: 10.1016/j.anireprosci.2009.03.002] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2009] [Revised: 02/22/2009] [Accepted: 03/04/2009] [Indexed: 11/15/2022]
Abstract
Sixteen Arab lactating mares belonging to Al-Zahraa Arab Horse Stud underwent two ultrasound examinations at 3 weeks interval starting from the day of demonstration of foaling heat. In addition, daily blood samples were collected from parturition until after exhibiting first postpartum estrus (day 11) with daily observation of estrous signs. Both leptin and estradiol hormones were assayed. Mean day of foaling heat was 8.9+/-0.9 day. Most mares came in foaling heat during days 9 and 10 had high conception rate compared to those who came in estrus earlier or later. Estradiol levels were high after day of foaling then decrease after expression of foaling heat. But leptin levels increase from day 8 to day 10 compared to other days before and after the first ovulation. A significant positive correlation was found between estradiol and leptin (r=0.58, p<0.025). The positive correlation between leptin and estradiol led us to suggest that leptin hormone plays an important role in ovulation of the first postpartum estrus in mares.
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Affiliation(s)
- Amal M Abo El-Maaty
- Animal Reproduction and Al Department, Veterinary Division, National Research Center, Dokki, Giza 12311, Egypt.
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48
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Whitley NC, O'Brien DJ, Quinn RW, Keisler DH, Walker EL, Brown MA. Milk leptin in sows and blood leptin and growth of their offspring1,2. J Anim Sci 2009; 87:1659-63. [DOI: 10.2527/jas.2008-1568] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
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Forhead AJ, Fowden AL. The hungry fetus? Role of leptin as a nutritional signal before birth. J Physiol 2009; 587:1145-52. [PMID: 19188249 DOI: 10.1113/jphysiol.2008.167072] [Citation(s) in RCA: 87] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023] Open
Abstract
In adult animals, leptin is an adipose-derived hormone that is important primarily in the regulation of energy balance during short- and long-term changes in nutritional state. Expression of leptin and its receptors is widespread in fetal and placental tissues, although the role of leptin as a nutritional signal in utero is unclear. Before birth, leptin concentration correlates with several indices of fetal growth, and may be an endocrine marker of fetal size and energy stores in the control of metabolism and maturation of fetal tissues. In addition, leptin synthesis and plasma concentration can be modified by insulin, glucocorticoids, thyroid hormones and oxygen availability in utero, and therefore, leptin may be part of the hormonal response to changes in the intrauterine environment. Evidence is emerging to show that leptin has actions before birth that are tissue-specific and may occur in critical periods of development. Some of these actions are involved in the growth and development of the fetus and others have long-term consequences for the control of energy balance in adult life.
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Affiliation(s)
- Alison J Forhead
- Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3EG, UK.
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Lim G, Wang S, Zhang Y, Tian Y, Mao J. Spinal leptin contributes to the pathogenesis of neuropathic pain in rodents. J Clin Invest 2009; 119:295-304. [PMID: 19139561 DOI: 10.1172/jci36785] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2008] [Accepted: 11/12/2008] [Indexed: 12/27/2022] Open
Abstract
Pain after nerve injury, a phenomenon referred to as neuropathic pain, is a debilitating clinical condition, but the underlying mechanisms remain unclear. As leptin, an adipocytokine produced mainly by nonneuronal tissue, has been implicated in the regulation of neuronal functions, we examined the role of leptin in neuropathic pain using a rat model of the condition chronic constriction sciatic nerve injury (CCI). We report that leptin critically contributed to pain behaviors following CCI. Specifically, spinal administration of a leptin antagonist prevented and reversed neuropathic pain behaviors in rats. Further examination revealed that levels of both leptin and the long form of the leptin receptor (Ob-Rb) were substantially increased within the ipsilateral spinal cord dorsal horn after peripheral nerve injury. Mechanistic studies showed that leptin upregulated the expression of both the spinal NMDA receptor and IL-1beta through the JAK/STAT pathway. Furthermore, these CCI-induced behavioral and cellular responses were diminished in leptin-deficient mice and mimicked by spinal administration of exogenous leptin in naive rats. Our findings reveal a critical role for spinal leptin in the pathogenesis of neuropathic pain and suggest what we believe to be a novel form of nonneuronal and neuronal interactions in the mechanisms of pathological pain.
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Affiliation(s)
- Grewo Lim
- MGH Center for Translational Pain Research, Department of Anesthesia and Critical Care, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
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