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Ikeda Y, Kawamura R, Tabara Y, Maruyama K, Shiokawa D, Takakado M, Hadate T, Takata Y, Ohashi J, Saito I, Ogawa Y, Osawa H. Genetic variation in the RETN promoter, accompanied by latent sarcopenic obesity, led to insulin resistance in a Japanese cohort: the Toon Genome Study. Diabetologia 2025; 68:854-865. [PMID: 39670999 PMCID: PMC11950018 DOI: 10.1007/s00125-024-06322-1] [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] [Received: 01/18/2024] [Accepted: 09/11/2024] [Indexed: 12/14/2024]
Abstract
AIMS/HYPOTHESIS Resistin, inducing insulin resistance, is elevated in the sera of individuals with the G-A haplotype at c.-420 C>G (rs1862513) and c.-358 G>A (rs3219175). This haplotype is associated with visceral obesity and low grip strength. To elucidate the hidden relationship between the G-A haplotype and insulin resistance, integration of specific phenotypes defined by body composition and 75 g OGTT would be a promising strategy. METHODS The 803 Japanese participants (average age: 62 years), attending annual medical checkups, were evaluated every 5 years. Participants were categorised by skeletal muscle mass, visceral fat score and OGTT results. Hierarchical clustering was performed using body composition and glucose metabolism parameters. Whole blood cells from participants homozygous for the G-A or C-G haplotype (n=25 and 33, respectively), matched for age, sex and BMI, using propensity score matching, were used for RNA-seq, pathway analysis and RT-PCR. RESULTS Multivariate analysis showed that individuals with the G-A haplotype, when accompanied by latent skeletal muscle loss and visceral obesity (latent sarcopenic obesity), presented a pronounced deterioration in insulin resistance over a 5 year period. Cluster 2, identified using hierarchical clustering, was characterised by low skeletal muscle mass, visceral obesity and insulin resistance. This cluster, with the G-A haplotype, demonstrated deterioration in insulin resistance. RNA-seq and RT-PCR revealed altered expression of mitophagy-related genes in whole blood cells of the G-A homozygotes. CONCLUSIONS/INTERPRETATION The G-A haplotype, accompanied by latent low skeletal muscle mass and visceral obesity, led to the deterioration of insulin resistance over a 5 year period in this cohort, possibly through the altered expression of mitophagy-related genes.
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Affiliation(s)
- Yosuke Ikeda
- Department of Diabetes and Molecular Genetics, Ehime University Graduate School of Medicine, Ehime, Japan
| | - Ryoichi Kawamura
- Department of Diabetes and Molecular Genetics, Ehime University Graduate School of Medicine, Ehime, Japan
| | - Yasuharu Tabara
- Graduate School of Public Health, Shizuoka Graduate University of Public Health, Shizuoka, Japan
- Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Koutatsu Maruyama
- Department of Bioscience, Graduate School of Agriculture, Ehime University, Ehime, Japan
| | | | - Misaki Takakado
- Department of Diabetes and Molecular Genetics, Ehime University Graduate School of Medicine, Ehime, Japan
| | - Toshimi Hadate
- Department of Diabetes and Molecular Genetics, Ehime University Graduate School of Medicine, Ehime, Japan
| | - Yasunori Takata
- Department of Diabetes and Molecular Genetics, Ehime University Graduate School of Medicine, Ehime, Japan
| | - Jun Ohashi
- Department of Biological Sciences, Graduate School of Science, University of Tokyo, Tokyo, Japan
| | - Isao Saito
- Department of Public Health and Epidemiology, Faculty of Medicine, Oita University, Oita, Japan
| | - Yoshihiro Ogawa
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Haruhiko Osawa
- Department of Diabetes and Molecular Genetics, Ehime University Graduate School of Medicine, Ehime, Japan.
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Rompou AV, Bletsa G, Tsakogiannis D, Theocharis S, Vassiliu P, Danias N. An Updated Review of Resistin and Colorectal Cancer. Cureus 2024; 16:e65403. [PMID: 39184804 PMCID: PMC11344879 DOI: 10.7759/cureus.65403] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/25/2024] [Indexed: 08/27/2024] Open
Abstract
Resistin is one of the most important adipokines, and its role lies mainly in controlling insulin sensitivity and inflammation. However, over the last years, the study of resistin gained increased popularity since it was proved that there is a considerable relationship between high levels of resistin and obesity as well as obesity-induced diseases, including diabetes, cardiovascular disorders, and cancer. Regarding cancer risk, circulating resistin levels have been correlated with several types of cancer, including colorectal, breast, lung, endometrial, gastroesophageal, prostate, renal, and pancreatic cancer. Colorectal cancer is regarded as a multi-pathway disease. Several pathophysiological features seem to promote colorectal cancer (CRC) such as chronic inflammation, insulin resistance, and obesity. Even though the molecular mechanisms involved in CRC development remain rather vague, it is widely accepted that several biochemical factors promote CRC by releasing augmented pro-inflammatory cytokines, like IGF-I, insulin, sex-steroid hormones, and adipokines. A wide range of research studies has focused on evaluating the impact of circulating resistin levels on CRC risk and determining the efficacy of chemotherapy in CRC patients by measuring resistin levels. Moreover, significant outcomes have emerged regarding the association of specific single nucleotide polymorphisms (SNPs) in the resistin gene and CRC risk. The present study reviewed the role of circulating resistin levels in CRC development and shed light on specific resistin gene SNPs implicated in the disease's development. Finally, we analyzed the impact of resistin levels on the effectiveness of chemotherapy and further discussed whether resistin can be regarded as a valuable biomarker for CRC prognosis and treatment. Resistin is one of the most important adipokines, and its role lies mainly in controlling insulin sensitivity and inflammation. However, over the last years, the study of resistin gained increased popularity since it was proved that there is a considerable relationship between high levels of resistin and obesity as well as obesity-induced diseases, including diabetes, cardiovascular disorders, and cancer. This review discusses the aberrant expression of resistin and its receptors, its diverse downstream signaling, and its impact on tumor growth, metastasis, angiogenesis, and therapy resistance to support its clinical exploitation in biomarker and therapeutic development.
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Affiliation(s)
- Aliki Vaia Rompou
- Department of Colorectal Surgery, Guy's and St Thomas' NHS Foundation Trust, London, GBR
| | - Garyfalia Bletsa
- Department of Medicine, Research Center, Hellenic Anticancer Institute, Athens, GRC
| | | | - Stamatios Theocharis
- Department of Pathology, National and Kapodistrian University of Athens, Athens, GRC
| | - Panteleimon Vassiliu
- Fourth Department of Surgery, Attikon University Hospital, National and Kapodistrian University of Athens, Athens, GRC
| | - Nick Danias
- Fourth Department of Surgery, Attikon University Hospital, National and Kapodistrian University of Athens, Athens, GRC
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Hua K, Li T, He Y, Guan A, Chen L, Gao Y, Xu Q, Wang H, Luo R, Zhao L, Jin H. Resistin secreted by porcine alveolar macrophages leads to endothelial cell dysfunction during Haemophilus parasuis infection. Virulence 2023; 14:2171636. [PMID: 36694280 PMCID: PMC9928480 DOI: 10.1080/21505594.2023.2171636] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023] Open
Abstract
Haemophilus parasuis (H. parasuis) causes exudative inflammation, implying endothelial dysfunction during pathogen infection. However, so far, the molecular mechanism of endothelial dysfunction caused by H. parasuis has not been clarified. By using the transwell-based cell co-culture system, we demonstrate that knocking out resistin in porcine alveolar macrophages (PAMs) dramatically attenuated endothelial monolayer damage caused by H. parasuis. The resistin secreted by PAMs inhibited the expression of the tight junction proteins claudin-5 and occludin rather than the adherens junction protein VE-cadherin in co-cultured porcine aortic endothelial cells (PAECs). Furthermore, we demonstrate that resistin regulated claudin-5 and occludin expression and monolayer PAEC permeability in an LKB1/AMPK/mTOR pathway-dependent manner. Additionally, we reveal that the outer membrane lipoprotein gene lppA in H. parasuis induced resistin expression in PAMs, as deleting lppA reduced resistin expression in H. parasuis-infected PAMs, causing a significant change in LKB1/AMPK/mTOR pathway activity in co-cultured PAECs, thereby restoring tight junction protein levels and endothelial monolayer permeability. Thus, we postulate that the H. parasuis lppA gene enhances resistin production in PAMs, disrupting tight junctions in PAECs and causing endothelial barrier dysfunction. These findings elucidate the pathogenic mechanism of exudative inflammation caused by H. parasuis for the first time and provide a more profound angle of acute exudative inflammation caused by bacteria.
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Affiliation(s)
- Kexin Hua
- State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China,College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China,Hubei Provincial Key Laboratory of Preventive Veterinary Medicine, Huazhong Agricultural University, China
| | - Tingting Li
- Department of Animal Disease Diagnosis, Hubei Animal Disease Prevention and Control Centre, Wuhan, China
| | - Yanling He
- State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China,College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China,Hubei Provincial Key Laboratory of Preventive Veterinary Medicine, Huazhong Agricultural University, China
| | - Aohan Guan
- State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China,College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China,Hubei Provincial Key Laboratory of Preventive Veterinary Medicine, Huazhong Agricultural University, China
| | - Liying Chen
- State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China,College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China,Hubei Provincial Key Laboratory of Preventive Veterinary Medicine, Huazhong Agricultural University, China
| | - Yuan Gao
- State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China,College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China,Hubei Provincial Key Laboratory of Preventive Veterinary Medicine, Huazhong Agricultural University, China
| | - Qianshuan Xu
- State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China,College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China,Hubei Provincial Key Laboratory of Preventive Veterinary Medicine, Huazhong Agricultural University, China
| | - Haoyu Wang
- State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China,College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China,Hubei Provincial Key Laboratory of Preventive Veterinary Medicine, Huazhong Agricultural University, China
| | - Rui Luo
- State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China,College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China,Hubei Provincial Key Laboratory of Preventive Veterinary Medicine, Huazhong Agricultural University, China
| | - Ling Zhao
- State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China,College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China,Hubei Provincial Key Laboratory of Preventive Veterinary Medicine, Huazhong Agricultural University, China
| | - Hui Jin
- State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China,College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China,Hubei Provincial Key Laboratory of Preventive Veterinary Medicine, Huazhong Agricultural University, China,CONTACT Hui Jin
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Respekta N, Pich K, Mlyczyńska E, Dobrzyń K, Ramé C, Kamiński T, Smolińska N, Dupont J, Rak A. Plasma level of omentin-1, its expression, and its regulation by gonadotropin-releasing hormone and gonadotropins in porcine anterior pituitary cells. Sci Rep 2023; 13:19325. [PMID: 37935840 PMCID: PMC10630491 DOI: 10.1038/s41598-023-46742-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2023] [Accepted: 11/04/2023] [Indexed: 11/09/2023] Open
Abstract
Omentin-1 (OMNT1) is an adipokine involved in the regulation of energy metabolism, insulin sensitivity, and reproduction. The present study was the first to investigate the plasma levels and expression of OMNT1 in the anterior pituitary (AP) gland on days 2-3, 10-12, 14-16, and 17-19 of the estrous cycle of normal-weight Large White (LW) and fat Meishan (MS) pigs. Next, we determined the effect of GnRH, LH, and FSH on the OMNT1 levels in cultured AP cells. The gene and protein expression of OMNT1 in AP fluctuated during the estrous cycle, with a higher expression in MS than in LW (except on days 10-12). However, plasma levels of OMNT1 were higher in LW than in MS. OMNT1 was localized in somatotrophs, lactotrophs, thyrotrophs, and gonadotrophs. In LW pituitary cells, GnRH and gonadotropins stimulated OMNT1 protein expression (except FSH on days 14-16) and had no effect on OMNT1 levels in the culture medium. In MS pituitary cells, we observed that GnRH and LH increased while FSH decreased OMNT1 protein expression. These findings showed OMNT1 expression and regulation in the porcine AP and suggested that OMNT1 could be a new player modifying the pituitary functions.
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Affiliation(s)
- Natalia Respekta
- Laboratory of Physiology and Toxicology of Reproduction, Institute of Zoology and Biomedical Research, Jagiellonian University, Gronostajowa 9 Street, 30-387, Kraków, Poland
- Doctoral School of Exact and Natural Sciences, Jagiellonian University, Kraków, Poland
| | - Karolina Pich
- Laboratory of Physiology and Toxicology of Reproduction, Institute of Zoology and Biomedical Research, Jagiellonian University, Gronostajowa 9 Street, 30-387, Kraków, Poland
- Doctoral School of Exact and Natural Sciences, Jagiellonian University, Kraków, Poland
| | - Ewa Mlyczyńska
- Laboratory of Physiology and Toxicology of Reproduction, Institute of Zoology and Biomedical Research, Jagiellonian University, Gronostajowa 9 Street, 30-387, Kraków, Poland
- Doctoral School of Exact and Natural Sciences, Jagiellonian University, Kraków, Poland
| | - Kamil Dobrzyń
- Department of Zoology, Faculty of Biology and Biotechnology, University of Warmia and Mazury, Kortowo, Olsztyn, Poland
| | - Christelle Ramé
- INRAE, UMR85, Unité Physiologie de la Reproduction et des Comportements, Nouzilly, France
| | - Tadeusz Kamiński
- Department of Animal Anatomy and Physiology, Faculty of Biology and Biotechnology, University of Warmia and Mazury, Kortowo, Olsztyn, Poland
| | - Nina Smolińska
- Department of Animal Anatomy and Physiology, Faculty of Biology and Biotechnology, University of Warmia and Mazury, Kortowo, Olsztyn, Poland
| | - Joëlle Dupont
- INRAE, UMR85, Unité Physiologie de la Reproduction et des Comportements, Nouzilly, France
| | - Agnieszka Rak
- Laboratory of Physiology and Toxicology of Reproduction, Institute of Zoology and Biomedical Research, Jagiellonian University, Gronostajowa 9 Street, 30-387, Kraków, Poland.
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de Luis Román D, Primo Martín D, Izaola Jáuregui O. Association of resistin (rs3138167) gene polymorphism with metabolic response after a hypocaloric Mediterranean diet. NUTR HOSP 2023. [PMID: 37929859 DOI: 10.20960/nh.04763] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2023] Open
Abstract
BACKGROUND the single nucleotide polymorphism (SNP) (rs3138167) of resistin (RETN) gene is a polymorphism that has been associated with metabolic disorder in obese subjects and its effect on the metabolic response after a dietary intervention has not been evaluated. OBJECTIVE our aim was to analyze the effects of the rs3138167 RETN gene polymorphism on metabolic changes secondary to weight loss with a hypocaloric diet with a Mediterranean pattern. METHOD one thousand and eight Caucasian obese patients were evaluated. Before and after 12 weeks on a hypocaloric diet with Mediterranean pattern, an anthropometric evaluation and a biochemical analysis were performed. The statistical analysis was performed as a dominant model (CC vs CT + TT). RESULTS the values of insulin, HOMA-IR and resistin were higher in T allele carriers than non-T allele carriers in pre- and post-intervention time. In non-T allele carriers, resistin, insulin, HOMA-IR, triglycerides and C-reactive protein levels decreased. The improvement was statistically superior in non-T allele carriers; resistin (-1.2 ± 0.2 ng/dl; p = 0.02), triglycerides (-18.3 ± 4.3 mg/dl; p = 0.02), C-reactive protein (-2.6 ± 0.3 mg/dl; p = 0.02), insulin -4.4 ± 1.9 mUI/l; p = 0.02) and HOMA-IR (-2.1 ± 0.7; p = 0.03). CONCLUSION we report an association of rs3138167 with a worse metabolic response (insulin, HOMA-IR, triglyceride and C-reactive protein) in T allele carriers after weight loss with a hypocaloric diet with Mediterranean pattern.
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Affiliation(s)
- Daniel de Luis Román
- Centro de Investigación de Endocrinología y Nutrición Clínica de Valladolid (IENVA). Facultad de Medicina. Universidad de Valladolid
| | - David Primo Martín
- Centro de Investigación de Endocrinología y Nutrición Clínica de Valladolid (IENVA). Facultad de Medicina. Universidad de Valladolid
| | - Olatz Izaola Jáuregui
- Centro de Investigación de Endocrinología y Nutrición Clínica de Valladolid (IENVA). Facultad de Medicina. Universidad de Valladolid
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Garbuzova EV, Khudiakova AD, Shcherbakova LV, Kashtanova EV, Polonskaya YV, Stakhneva EM, Ragino YI. Associations of Adipocytokines and Early Renal Dysfunction in Young People on the Background of Dyslipidemia. J Pers Med 2023; 13:1238. [PMID: 37623488 PMCID: PMC10455902 DOI: 10.3390/jpm13081238] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2023] [Revised: 07/28/2023] [Accepted: 08/05/2023] [Indexed: 08/26/2023] Open
Abstract
BACKGROUND There are data supporting the idea that atherogenic dyslipidemia is a risk factor for CKD and reduced GFR. The aim was to evaluate the associations between adipocytokines and early renal dysfunction in young people with dyslipidemia. MATERIALS AND METHODS A population study was conducted in IIPM-Branch of IC&G SB RAS, in 2013-2017. Furthermore, 1033 people were included in the study (469 men (45.4%) and 564 women (54.6%)). The study included blood sampling, anthropometric data, and adipokines by multiplex analysis. RESULTS Among people with reduced kidney function and DLP, men were 3.1 times more common than without DLP, women smoked 2 times less often, arterial hypertension was 7.8 times more common, and abdominal obesity was 2.7 times more common (and women with DLP were 3 times more likely than those without DLP). An increase in the level of resistin by 1 mcg/mL was associated with an increased chance of having renal dysfunction by 0.2%. An increase in the level of GIP was associated with an increased chance of having renal dysfunction by 1.1%. CONCLUSIONS In young people with dyslipidemia, regardless of the presence of abdominal obesity, resistin and GIP are associated with the presence of renal dysfunction.
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Affiliation(s)
| | | | | | | | | | | | - Yulia I. Ragino
- Research Institute of Internal and Preventive Medicine–Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences (IIPM—Branch of IC&G SB RAS), B. Bogatkova Str., 175/1, 630089 Novosibirsk, Russia; (E.V.G.); (A.D.K.); (L.V.S.); (E.V.K.); (Y.V.P.); (E.M.S.)
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de Luis DA, Primo D, Izaola O, Aller R. Role of resistin (rs7139228) gene polymorphism with metabolic response after a hypocaloric mediterranean diet. ENDOCRINOL DIAB NUTR 2023; 70:88-97. [PMID: 36841628 DOI: 10.1016/j.endien.2022.10.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2022] [Accepted: 10/16/2022] [Indexed: 02/25/2023]
Abstract
BACKGROUND The SNP (rs7139228) of the RETN gene is a polymorphism that has been associated with metabolic disorder in subjects with obesity, and its effect on metabolic response after dietary intervention has not been evaluated. OBJECTIVE Our objective was to analyse the effects of the polymorphism of the RETN gene rs7139228 on metabolic changes secondary to weight loss with a hypocaloric Mediterranean diet. DESIGN 1000 obese Caucasian patients were evaluated. An anthropometric evaluation and a biochemical analysis were performed before and after 12 weeks of a hypocaloric Mediterranean diet. The statistical analysis was performed as a dominant model (GG vs GA+AA). RESULTS Improvements in anthropometric parameters, leptin levels and systolic blood pressure were similar in both genotype groups. In non- A allele carriers, levels of resistin, insulin, HOMA-IR, triglycerides and C-reactive protein decreased. The improvements were statistically significant in this group; resistin (-1.3+0.1ng/dL: p=0.02), triglycerides (-22.9+4.9mg/dl: p=0.02), CRP (-2.7+0 0.4mg/dl: p=0.02), insulin -6.5+1.8 mIU/L: p=0.02) and HOMA-IR (-2.2+0.8: p=0, 03). In addition, insulin, HOMA-IR and resistin levels were higher in A allele carriers than in non-carriers. Finally, the prevalence of metabolic syndrome and hyperglycaemia were higher in A allele carriers, and these percentages only decreased after intervention in non-A allele carriers. CONCLUSION The A rs7139228 allele is associated with a worse metabolic response (insulin, HOMA-IR, triglycerides and CRP) after weight loss with a hypocaloric Mediterranean diet. A non-significant decrease in the prevalence of metabolic syndrome and hyperglycaemia were detected in A allele carriers.
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Affiliation(s)
- Daniel Antonio de Luis
- Centro de Investigación de Endocrinología y Nutrición, Facultad de Medicina y Svo Endocrinología y Nutrición Hospital Clínico Universitario, Universidad de Valladolid, Valladolid, Spain.
| | - David Primo
- Centro de Investigación de Endocrinología y Nutrición, Facultad de Medicina y Svo Endocrinología y Nutrición Hospital Clínico Universitario, Universidad de Valladolid, Valladolid, Spain
| | - Olatz Izaola
- Centro de Investigación de Endocrinología y Nutrición, Facultad de Medicina y Svo Endocrinología y Nutrición Hospital Clínico Universitario, Universidad de Valladolid, Valladolid, Spain
| | - Rocío Aller
- Centro de Investigación de Endocrinología y Nutrición, Facultad de Medicina y Svo Endocrinología y Nutrición Hospital Clínico Universitario, Universidad de Valladolid, Valladolid, Spain
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Hue I, Capilla E, Rosell-Moll E, Balbuena-Pecino S, Goffette V, Gabillard JC, Navarro I. Recent advances in the crosstalk between adipose, muscle and bone tissues in fish. Front Endocrinol (Lausanne) 2023; 14:1155202. [PMID: 36998471 PMCID: PMC10043431 DOI: 10.3389/fendo.2023.1155202] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2023] [Accepted: 02/27/2023] [Indexed: 03/17/2023] Open
Abstract
Control of tissue metabolism and growth involves interactions between organs, tissues, and cell types, mediated by cytokines or direct communication through cellular exchanges. Indeed, over the past decades, many peptides produced by adipose tissue, skeletal muscle and bone named adipokines, myokines and osteokines respectively, have been identified in mammals playing key roles in organ/tissue development and function. Some of them are released into the circulation acting as classical hormones, but they can also act locally showing autocrine/paracrine effects. In recent years, some of these cytokines have been identified in fish models of biomedical or agronomic interest. In this review, we will present their state of the art focusing on local actions and inter-tissue effects. Adipokines reported in fish adipocytes include adiponectin and leptin among others. We will focus on their structure characteristics, gene expression, receptors, and effects, in the adipose tissue itself, mainly regulating cell differentiation and metabolism, but in muscle and bone as target tissues too. Moreover, lipid metabolites, named lipokines, can also act as signaling molecules regulating metabolic homeostasis. Regarding myokines, the best documented in fish are myostatin and the insulin-like growth factors. This review summarizes their characteristics at a molecular level, and describes both, autocrine effects and interactions with adipose tissue and bone. Nonetheless, our understanding of the functions and mechanisms of action of many of these cytokines is still largely incomplete in fish, especially concerning osteokines (i.e., osteocalcin), whose potential cross talking roles remain to be elucidated. Furthermore, by using selective breeding or genetic tools, the formation of a specific tissue can be altered, highlighting the consequences on other tissues, and allowing the identification of communication signals. The specific effects of identified cytokines validated through in vitro models or in vivo trials will be described. Moreover, future scientific fronts (i.e., exosomes) and tools (i.e., co-cultures, organoids) for a better understanding of inter-organ crosstalk in fish will also be presented. As a final consideration, further identification of molecules involved in inter-tissue communication will open new avenues of knowledge in the control of fish homeostasis, as well as possible strategies to be applied in aquaculture or biomedicine.
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Affiliation(s)
- Isabelle Hue
- Laboratory of Fish Physiology and Genomics, UR1037, Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement (INRAE), Rennes, France
| | - Encarnación Capilla
- Departament de Biologia Cel·lular, Fisiologia i Immunologia, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain
| | - Enrique Rosell-Moll
- Departament de Biologia Cel·lular, Fisiologia i Immunologia, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain
| | - Sara Balbuena-Pecino
- Departament de Biologia Cel·lular, Fisiologia i Immunologia, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain
| | - Valentine Goffette
- Laboratory of Fish Physiology and Genomics, UR1037, Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement (INRAE), Rennes, France
| | - Jean-Charles Gabillard
- Laboratory of Fish Physiology and Genomics, UR1037, Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement (INRAE), Rennes, France
| | - Isabel Navarro
- Departament de Biologia Cel·lular, Fisiologia i Immunologia, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain
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Regensburger M, Rasul Chaudhry S, Yasin H, Zhao Y, Stadlbauer A, Buchfelder M, Kinfe T. Emerging roles of leptin in Parkinson's disease: Chronic inflammation, neuroprotection and more? Brain Behav Immun 2023; 107:53-61. [PMID: 36150585 DOI: 10.1016/j.bbi.2022.09.010] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2022] [Revised: 08/22/2022] [Accepted: 09/16/2022] [Indexed: 12/13/2022] Open
Abstract
An increasing body of experimental evidence implicates a relationship between immunometabolic deterioration and the progression of Parkinson's disease (PD) with a dysregulation of central and peripheral neuroinflammatory networks mediated by circulating adipokines, in particular leptin. We screened the current literature on the role of adipokines in PD. Hence, we searched known databases (PubMed, MEDLINE/OVID) and reviewed original and review articles using the following terms: "leptin/ObR", "Parkinson's disease", "immune-metabolism", "biomarkers" and "neuroinflammation". Focusing on leptin, we summarize and discuss the existing in vivo and in vitro evidence on how adipokines may be protective against neurodegeneration, but at the same time contribute to the progression of PD. These components of the adipose brain axis represent a hitherto underestimated pathway to study systemic influences on dopaminergic degeneration. In addition, we give a comprehensive update on the potential of adjunctive therapeutics in PD targeting leptin, leptin-receptors, and associated pathways. Further experimental and clinical trials are needed to elucidate the mechanisms of action and the value of central and peripheral adipose-immune-metabolism molecular phenotyping in order to develop and validate the differential roles of different adipokines as potential therapeutic target for PD patients.
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Affiliation(s)
- Martin Regensburger
- Department of Molecular Neurology, Friedrich-Alexander University (FAU), Erlangen-Nürnberg, 91054 Erlangen, Germany; Center for Rare Diseases Erlangen (ZSEER), University Hospital Erlangen, 91054 Erlangen, Germany
| | - Shafqat Rasul Chaudhry
- Obaid Noor Institute of Medical Sciences (ONIMS), Mianwali, Pakistan; Shifa College of Pharmaceutical Sciences, Shifa Tameer-e-Millat University, 44000 Islamabad, Pakistan
| | - Hammad Yasin
- Shifa College of Pharmaceutical Sciences, Shifa Tameer-e-Millat University, 44000 Islamabad, Pakistan
| | - Yining Zhao
- Department of Neurosurgery, Friedrich-Alexander University (FAU), Erlangen-Nürnberg, 91054 Erlangen, Germany
| | - Andreas Stadlbauer
- Department of Neurosurgery, Friedrich-Alexander University (FAU), Erlangen-Nürnberg, 91054 Erlangen, Germany
| | - Michael Buchfelder
- Department of Neurosurgery, Friedrich-Alexander University (FAU), Erlangen-Nürnberg, 91054 Erlangen, Germany
| | - Thomas Kinfe
- Division of Functional Neurosurgery and Stereotaxy, Friedrich-Alexander University (FAU), Erlangen-Nürnberg, 91054 Erlangen, Germany.
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10
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Papel del polimorfismo del gen de la resistina (rs7139228) en la respuesta metabólica tras una dieta mediterránea hipocalórica. ENDOCRINOL DIAB NUTR 2022. [DOI: 10.1016/j.endinu.2022.10.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
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11
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Kirichenko TV, Markina YV, Bogatyreva AI, Tolstik TV, Varaeva YR, Starodubova AV. The Role of Adipokines in Inflammatory Mechanisms of Obesity. Int J Mol Sci 2022; 23:ijms232314982. [PMID: 36499312 PMCID: PMC9740598 DOI: 10.3390/ijms232314982] [Citation(s) in RCA: 101] [Impact Index Per Article: 33.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2022] [Revised: 11/25/2022] [Accepted: 11/27/2022] [Indexed: 12/02/2022] Open
Abstract
Adipokines are currently widely studied cellular signaling proteins produced by adipose tissue and involved in various processes, including inflammation; energy and appetite modulation; lipid and glucose metabolism; insulin sensitivity; endothelial cell functioning; angiogenesis; the regulation of blood pressure; and hemostasis. The current review attempted to highlight the key functions of adipokines in the inflammatory mechanisms of obesity, its complications, and its associated diseases. An extensive search for materials on the role of adipokines in the pathogenesis of obesity was conducted online using the PubMed and Scopus databases until October 2022.
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Affiliation(s)
- Tatiana V. Kirichenko
- Petrovsky National Research Center of Surgery, 119991 Moscow, Russia
- Chazov National Medical Research Center of Cardiology, 121552 Moscow, Russia
| | - Yuliya V. Markina
- Petrovsky National Research Center of Surgery, 119991 Moscow, Russia
- Correspondence:
| | | | | | - Yurgita R. Varaeva
- Federal Research Centre for Nutrition, Biotechnology and Food Safety, 109240 Moscow, Russia
| | - Antonina V. Starodubova
- Federal Research Centre for Nutrition, Biotechnology and Food Safety, 109240 Moscow, Russia
- Medical Faculty, Pirogov Russian National Research Medical University, 117997 Moscow, Russia
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12
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Neurometabolic Dysfunction in SPG11 Hereditary Spastic Paraplegia. Nutrients 2022; 14:nu14224803. [PMID: 36432490 PMCID: PMC9693816 DOI: 10.3390/nu14224803] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2022] [Accepted: 11/09/2022] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND Pathogenic variants in SPG11 cause the most common autosomal recessive complicated hereditary spastic paraplegia. Besides the prototypical combination of spastic paraplegia with a thin corpus callosum, obesity has increasingly been reported in this multisystem neurodegenerative disease. However, a detailed analysis of the metabolic state is lacking. METHODS In order to characterize metabolic alterations, a cross-sectional analysis was performed comparing SPG11 patients (n = 16) and matched healthy controls (n = 16). We quantified anthropometric parameters, body composition as determined by bioimpedance spectroscopy, and serum metabolic biomarkers, and we measured hypothalamic volume by high-field MRI. RESULTS Compared to healthy controls, SPG11 patients exhibited profound changes in body composition, characterized by increased fat tissue index, decreased lean tissue index, and decreased muscle mass. The presence of lymphedema correlated with increased extracellular fluid. The serum levels of the adipokines leptin, resistin, and progranulin were significantly altered in SPG11 while adiponectin and C1q/TNF-related protein 3 (CTRP-3) were unchanged. MRI volumetry revealed a decreased hypothalamic volume in SPG11 patients. CONCLUSIONS Body composition, adipokine levels, and hypothalamic volume are altered in SPG11. Our data indicate a link between obesity and hypothalamic neurodegeneration in SPG11 and imply that specific metabolic interventions may prevent obesity despite severely impaired mobility in SPG11.
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13
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Marchi PH, Vendramini THA, Perini MP, Zafalon RVA, Amaral AR, Ochamotto VA, Da Silveira JC, Dagli MLZ, Brunetto MA. Obesity, inflammation, and cancer in dogs: Review and perspectives. Front Vet Sci 2022; 9:1004122. [PMID: 36262532 PMCID: PMC9573962 DOI: 10.3389/fvets.2022.1004122] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Accepted: 08/31/2022] [Indexed: 11/13/2022] Open
Abstract
Obesity is the most common nutritional disease in dogs, and its prevalence has increased in recent decades. Several countries have demonstrated a prevalence of obesity in dogs similar to that observed in humans. Chronic low-grade inflammation is a prominent basis used to explain how obesity results in numerous negative health consequences. This is well known and understood, and recent studies have pointed to the association between obesity and predisposition to specific types of cancers and their complications. Such elucidations are important because, like obesity, the prevalence of cancer in dogs has increased in recent decades, establishing cancer as a significant cause of death for these animals. In the same way, intensive advances in technology in the field of human and veterinary medicine (which even proposes the use of animal models) have optimized existing therapeutic methods, led to the development of innovative treatments, and shortened the time to diagnosis of cancer. Despite the great challenges, this review aims to highlight the evidence obtained to date on the association between obesity, inflammation, and cancer in dogs, and the possible pathophysiological mechanisms that link obesity and carcinogenesis. The potential to control cancer in animals using existing knowledge is also presented.
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Affiliation(s)
- Pedro H. Marchi
- Pet Nutrology Research Center, Department of Animal Nutrition and Production of the School of Veterinary Medicine and Animal Science, University of São Paulo, Pirassununga, Brazil
| | - Thiago H. A. Vendramini
- Pet Nutrology Research Center, Department of Animal Nutrition and Production of the School of Veterinary Medicine and Animal Science, University of São Paulo, Pirassununga, Brazil
| | - Mariana P. Perini
- Pet Nutrology Research Center, Department of Animal Nutrition and Production of the School of Veterinary Medicine and Animal Science, University of São Paulo, Pirassununga, Brazil
| | - Rafael V. A. Zafalon
- Pet Nutrology Research Center, Department of Animal Nutrition and Production of the School of Veterinary Medicine and Animal Science, University of São Paulo, Pirassununga, Brazil
| | - Andressa R. Amaral
- Veterinary Nutrology Service, Veterinary Teaching Hospital of the School of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo, Brazil
| | - Vanessa A. Ochamotto
- Pet Nutrology Research Center, Department of Animal Nutrition and Production of the School of Veterinary Medicine and Animal Science, University of São Paulo, Pirassununga, Brazil
| | - Juliano C. Da Silveira
- Laboratory of Molecular, Morphophysiology and Development (LMMD), Department of Veterinary Medicine, Faculty of Animal Science and Food Engineering, University of São Paulo, Pirassununga, Brazil
| | - Maria L. Z. Dagli
- Laboratory of Experimental and Comparative Oncology, Department of Pathology, School of Veterinary Medicine and Animal Science of the University of São Paulo, São Paulo, Brazil
| | - Marcio A. Brunetto
- Pet Nutrology Research Center, Department of Animal Nutrition and Production of the School of Veterinary Medicine and Animal Science, University of São Paulo, Pirassununga, Brazil,Veterinary Nutrology Service, Veterinary Teaching Hospital of the School of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo, Brazil,*Correspondence: Marcio A. Brunetto
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14
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Hua K, Wang M, Jin Y, Gao Y, Luo R, Bi D, Zhou R, Jin H. P38 MAPK pathway regulates the expression of resistin in porcine alveolar macrophages via Ets2 during Haemophilus parasuis stimulation. DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY 2022; 128:104327. [PMID: 34863954 DOI: 10.1016/j.dci.2021.104327] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/02/2021] [Revised: 11/30/2021] [Accepted: 11/30/2021] [Indexed: 06/13/2023]
Abstract
Haemophilus parasuis is a widespread bacterial pathogen causing acute systemic inflammation and leading to the sudden death of piglets. Resistin, a multifunctional peptide hormone previously demonstrated to influence the inflammation in porcine, was extremely increased in H. parasuis-infected tissues. However, the mechanism of resistin expression regulation in porcine, especially during pathogen infection, remains unclear. In the present study, we explored for the first time the transcription factor and signaling pathway mediating the expression of pig resistin during H. parasuis stimulation. We found that H. parasuis induced the expression of pig resistin in a time- and dose-dependent manner via the transcription factor Ets2 in porcine alveolar macrophages during H. parasuis stimulation. Moreover, the expression of Ets2 was mediated by the activation of the p38 MAPK pathway induced by H. parasuis, thus promoting resistin production. These results revealed a novel view of the molecular mechanism of pig resistin production during acute inflammation induced by pathogenic bacteria.
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Affiliation(s)
- Kexin Hua
- State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, China; College of Veterinary Medicine, Huazhong Agricultural University, China; Hubei Provincial Key Laboratory of Preventive Veterinary Medicine, Huazhong Agricultural University, China
| | - Mingyang Wang
- State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, China; College of Veterinary Medicine, Huazhong Agricultural University, China; Hubei Provincial Key Laboratory of Preventive Veterinary Medicine, Huazhong Agricultural University, China
| | - Yishun Jin
- State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, China; College of Veterinary Medicine, Huazhong Agricultural University, China; Hubei Provincial Key Laboratory of Preventive Veterinary Medicine, Huazhong Agricultural University, China
| | - Yuan Gao
- State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, China; College of Veterinary Medicine, Huazhong Agricultural University, China; Hubei Provincial Key Laboratory of Preventive Veterinary Medicine, Huazhong Agricultural University, China
| | - Rui Luo
- State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, China; College of Veterinary Medicine, Huazhong Agricultural University, China; Hubei Provincial Key Laboratory of Preventive Veterinary Medicine, Huazhong Agricultural University, China
| | - Dingren Bi
- State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, China; College of Veterinary Medicine, Huazhong Agricultural University, China; Hubei Provincial Key Laboratory of Preventive Veterinary Medicine, Huazhong Agricultural University, China
| | - Rui Zhou
- State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, China; College of Veterinary Medicine, Huazhong Agricultural University, China; Hubei Provincial Key Laboratory of Preventive Veterinary Medicine, Huazhong Agricultural University, China
| | - Hui Jin
- State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, China; College of Veterinary Medicine, Huazhong Agricultural University, China; Hubei Provincial Key Laboratory of Preventive Veterinary Medicine, Huazhong Agricultural University, China.
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15
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Santosa I, Shoji H, Awata K, Arai Y, Suganuma H, Shimizu T. Resistin in Urine and Breast Milk: Relation to Type of Feeding and Anthropometry at 1-Month. Pediatr Rep 2022; 14:86-92. [PMID: 35225882 PMCID: PMC8883882 DOI: 10.3390/pediatric14010013] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2021] [Revised: 01/31/2022] [Accepted: 02/04/2022] [Indexed: 02/04/2023] Open
Abstract
Breast milk contains adipokines such as resistin and leptin and is known for its protective effect against obesity and insulin resistance. This pilot study aims to evaluate the correlation between resistin levels, feeding types (breast milk and formula), and anthropometric parameters in healthy 1-month-old term infants. Urine and breast milk samples were collected from 32 infants and their mothers at 1 month postpartum. Twelve infants were included in the breastfed group, while thirteen infants comprised the breastfed-dominant mix-fed group, and seven infants the formula-dominant mix-fed group. Using ELISA kits, we analyzed resistin levels in the infants' urine and the mothers' breast milk, and leptin levels in breast milk. Urinary resistin levels among the three groups were not significantly different. There was no correlation between the following: urinary resistin levels in the breastfed group with resistin levels in breast milk; resistin levels in urine with infant's body weight and weight gain; resistin levels in breast milk with weight, age, and BMI of mothers and leptin levels in breast milk. This study suggests that the type of feeding does not affect resistin levels in term infants and resistin level does not affect growth in early infancy.
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Affiliation(s)
- Irena Santosa
- Department of Pediatrics and Adolescent Medicine, Graduate School of Medicine, Juntendo University, Tokyo 113-8421, Japan; (I.S.); (K.A.); (Y.A.); (T.S.)
| | - Hiromichi Shoji
- Department of Pediatrics and Adolescent Medicine, Graduate School of Medicine, Juntendo University, Tokyo 113-8421, Japan; (I.S.); (K.A.); (Y.A.); (T.S.)
- Correspondence:
| | - Kentaro Awata
- Department of Pediatrics and Adolescent Medicine, Graduate School of Medicine, Juntendo University, Tokyo 113-8421, Japan; (I.S.); (K.A.); (Y.A.); (T.S.)
| | - Yoshiteru Arai
- Department of Pediatrics and Adolescent Medicine, Graduate School of Medicine, Juntendo University, Tokyo 113-8421, Japan; (I.S.); (K.A.); (Y.A.); (T.S.)
| | - Hiroki Suganuma
- Department of Pediatrics, Faculty of Medicine, Juntendo University, Tokyo 113-8421, Japan;
| | - Toshiaki Shimizu
- Department of Pediatrics and Adolescent Medicine, Graduate School of Medicine, Juntendo University, Tokyo 113-8421, Japan; (I.S.); (K.A.); (Y.A.); (T.S.)
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16
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Šebunova N, Štšepetova J, Kullisaar T, Suija K, Rätsep A, Junkin I, Soeorg H, Lember M, Sillakivi T, Mändar R. Changes in adipokine levels and metabolic profiles following bariatric surgery. BMC Endocr Disord 2022; 22:33. [PMID: 35114975 PMCID: PMC8812034 DOI: 10.1186/s12902-022-00942-7] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2021] [Accepted: 01/19/2022] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Bariatric surgery is considered to be the most effective treatment option for weight reduction in obese patients. Abdominal obesity is frequently accompanied by metabolic syndrome (MS). Adipokines are cell signaling proteins that have direct impact upon the metabolic homeostasis. The purpose of this analysis was to evaluate the effect of bariatric surgery, including laparoscopic sleeve gastrectomy (LSG) and laparoscopic gastric bypass (LRYGB) on the adipokine levels and metabolic profile as well as MS and status of type 2 diabetes (T2D). METHODS We analyzed anthropometric parameters, blood levels of adipokines, vitamins, lipids and inflammatory markers in 30 bariatric surgery patients with obesity of class II or III 1 month before and 1 year after surgery as well as in 60 obese patients from general practice (GP) and 15 patients with normal body mass (control). RESULTS The BMI was significantly higher among patients before surgery and GP patients in comparison to control and post-surgery patients. The levels of glucose, cholesterol and LDL-cholesterol, triglyceride and hs-CRP were the highest in patients before surgery but decreased significantly after surgery, while the level of HDL-cholesterol increased after surgery. The levels of adiponectin increased and that of leptin decreased after surgery. The significant difference in the concentration of resistin was revealed between LSG and LRYGB methods. The relationship between resistin and vitamin D was also found. The patients with MS and T2D displayed significantly greater reduction in lipid markers and adipokine levels than the rest of patients. CONCLUSION Remarkable changes in levels of adipokines after bariatric surgery appear like increase in adiponectin and decrease in leptin levels. Significant improvement in anthropometric parameters, metabolic and inflammatory markers occurs, suggesting high potential for reduction of metabolic syndrome and risk for type 2 diabetes. We have shown for the first time ever that level of vitamin D may be involved in resistin regulation.
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Affiliation(s)
- Natalja Šebunova
- Department of Microbiology, Institute of Biomedicine and Translational Medicine, University of Tartu, Ravila street 19, 50411, Tartu, Estonia
| | - Jelena Štšepetova
- Department of Microbiology, Institute of Biomedicine and Translational Medicine, University of Tartu, Ravila street 19, 50411, Tartu, Estonia.
- Competence Centre on Health Technologies, Tartu, Estonia.
| | - Tiiu Kullisaar
- Department of Biochemistry, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia
| | - Kadri Suija
- Department of Family Medicine, Faculty of Medicine, Institute of Family Medicine and Public Health, University of Tartu, Tartu, Estonia
| | - Anneli Rätsep
- Department of Family Medicine, Faculty of Medicine, Institute of Family Medicine and Public Health, University of Tartu, Tartu, Estonia
| | - Igor Junkin
- Department of Family Medicine, Faculty of Medicine, Institute of Family Medicine and Public Health, University of Tartu, Tartu, Estonia
- Family Doctors Takker ja Sarapuu Ldt, Tartu, Estonia
| | - Hiie Soeorg
- Department of Microbiology, Institute of Biomedicine and Translational Medicine, University of Tartu, Ravila street 19, 50411, Tartu, Estonia
| | - Margus Lember
- Department of Internal Medicine, Faculty of Medicine, Institute of Clinical Medicine, University of Tartu, Tartu, Estonia
- Department of Internal Medicine, Tartu University Hospital, Tartu, Estonia
| | - Toomas Sillakivi
- Abdominal Surgery Department, Tartu University Hospital, Tartu, Estonia
- Department of Surgery, Faculty of Medicine, Institute of Clinical Medicine, University of Tartu, Tartu, Estonia
| | - Reet Mändar
- Department of Microbiology, Institute of Biomedicine and Translational Medicine, University of Tartu, Ravila street 19, 50411, Tartu, Estonia
- Competence Centre on Health Technologies, Tartu, Estonia
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17
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Askin L, Abus S, Tanriverdi O. Resistin and Cardiovascular Disease: A Review of the Current Literature Regarding Clinical and Pathological Relationships. Curr Cardiol Rev 2022; 18:e290721195114. [PMID: 34325643 PMCID: PMC9241124 DOI: 10.2174/1573403x17666210729101120] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2021] [Revised: 06/20/2021] [Accepted: 06/21/2021] [Indexed: 11/22/2022] Open
Abstract
Serum resistin, mainly secreted by the bone marrow, monocytes, and macrophages, contributes to many processes, including endothelial dysfunction, Vascular Smooth Muscle Cell (VSMC) proliferation, and atherothrombosis demonstrating effects on the development of hypertension and Coronary Artery Disease (CAD). Previously published clinical studies have shown that plasma resistin levels are significantly associated with cardiovascular disease risk factors and adverse clinical outcomes associated with the condition. Resistin is associated with vascular smooth muscle cell dysfunction in vitro, most plausibly due to its relationship with oxidative stress in advanced atherosclerosis whereas in vivo studies have shown resistin to be associated with intimal hyperplasia. We aimed to summarize the role of resistin on cardiovascular disease (CVD), as we could not find any review focused on the role of resistin on CVD.
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Affiliation(s)
- Lutfu Askin
- Department of Cardiology, Adiyaman Education and Research Hospital, Adiyaman, Turkey
| | - Sabri Abus
- Department of cardiology, Kahta State Hospital, Kâhta, Turkey
| | - Okan Tanriverdi
- Department of Cardiology, Adiyaman Education and Research Hospital, Adiyaman, Turkey
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18
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Fuentes-Romero B, Muñoz-Prieto A, Cerón JJ, Martín-Cuervo M, Iglesias-García M, Aguilera-Tejero E, Díez-Castro E. Measurement of Plasma Resistin Concentrations in Horses with Metabolic and Inflammatory Disorders. Animals (Basel) 2021; 12:ani12010077. [PMID: 35011183 PMCID: PMC8744951 DOI: 10.3390/ani12010077] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2021] [Revised: 12/27/2021] [Accepted: 12/29/2021] [Indexed: 11/24/2022] Open
Abstract
Simple Summary Obesity and its associated complications, such as metabolic syndrome, are an increasing problem in both humans and horses in the developed world. Adipose tissue is a key endocrine organ that communicates with other organs by multiple endocrine substances called adipokines. There is evidence to suggest that adipokines may contribute to the regulation of biological processes, such as metabolism, immunity, and inflammation. The aim of this study was to investigate the usefulness of one of these adipokines in horses, resistin, and its relationship with insulin dysregulation (ID) and inflammation. Seventy-two horses, included in one of the four following groups, were studied: healthy controls, horses with inflammatory conditions, horses with mild, and horses with severe ID. Plasma resistin concentrations were significantly different between groups, and the highest values were recorded in the inflammatory and severe ID groups. The lack of correlation of resistin with basal insulin concentration and the significant correlation of resistin with the inflammatory marker serum amyloid A suggest that, as is the case in humans, plasma resistin concentrations in horses are predominantly related to inflammatory conditions and not to ID. Abstract Obesity and its associated complications, such as metabolic syndrome, are an increasing problem in both humans and horses in the developed world. The expression patterns of resistin differ considerably between species. In rodents, resistin is expressed by adipocytes and is related to obesity and ID. In humans, resistin is predominantly produced by inflammatory cells, and resistin concentrations do not reflect the degree of obesity, although they may predict cardiovascular outcomes. The aim of this study was to investigate the usefulness of resistin and its relationship with ID and selected indicators of inflammation in horses. Seventy-two horses, included in one of the four following groups, were studied: healthy controls (C, n = 14), horses with inflammatory conditions (I, n = 21), horses with mild ID (ID1, n = 18), and horses with severe ID (ID2, n = 19). Plasma resistin concentrations were significantly different between groups and the higher values were recorded in the I and ID2 groups (C: 2.38 ± 1.69 ng/mL; I: 6.85 ± 8.38 ng/mL; ID1: 2.41 ± 2.70 ng/mL; ID2: 4.49 ± 3.08 ng/mL). Plasma resistin was not correlated with basal insulin concentrations. A significant (r = 0.336, p = 0.002) correlation was found between resistin and serum amyloid A. Our results show that, as is the case in humans, plasma resistin concentrations in horses are predominantly related to inflammatory conditions and not to ID. Horses with severe ID showed an elevation in resistin that may be secondary to the inflammatory status associated with metabolic syndrome.
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Affiliation(s)
- Beatriz Fuentes-Romero
- Department of Equine Internal Medicine, University of Extremadura, 10004 Cáceres, Spain;
- Correspondence:
| | - Alberto Muñoz-Prieto
- Interdisciplinary Laboratory of Clinical Pathology, Interlab-UMU, University of Murcia, 30003 Murcia, Spain; (A.M.-P.); (J.J.C.)
| | - José J. Cerón
- Interdisciplinary Laboratory of Clinical Pathology, Interlab-UMU, University of Murcia, 30003 Murcia, Spain; (A.M.-P.); (J.J.C.)
| | - María Martín-Cuervo
- Department of Equine Internal Medicine, University of Extremadura, 10004 Cáceres, Spain;
| | | | | | - Elisa Díez-Castro
- Department of Equine Internal Medicine, University of Córdoba, 14014 Córdoba, Spain; (E.A.-T.); (E.D.-C.)
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19
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de Luis D, Aller R, Izaola O, Primo D. Role of the rs10401670 variant in the resistin gene on the metabolic response after weight loss secondary to a high-fat hypocaloric diet with a Mediterranean pattern. J Hum Nutr Diet 2021; 35:722-730. [PMID: 34907604 DOI: 10.1111/jhn.12975] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2021] [Revised: 09/11/2021] [Accepted: 11/11/2021] [Indexed: 01/01/2023]
Abstract
BACKGROUND The single nucleotide polymorphism (SNP) (rs10401670) of the RETN gene has been associated with metabolic disorder in obese subjects and has scarcely been evaluated after dietary interventions. The present study aimed to analyse the effects of the rs10401670 RETN gene polymorphism on metabolic changes secondary to weight loss and secondary to a high-fat hypocaloric diet with a Mediterranean dietary pattern. METHODS A Caucasian population comprising 284 obese patients without diabetes mellitus was analysed. Before and after 3 months of a high-fat hypocaloric diet with a Mediterranean pattern, an anthropometric evaluation, an assessment of nutritional intake and a biochemical analysis were performed. A statistical analysis was conducted for the combined CT and TT as a group and for wild-type CC as a second group. RESULTS Decreases in weight, body mass index (BMI), fat mass, systolic blood pressure and waist circumference were similar in both genotypes groups. In T allele carriers, insulin, homeostatic model assessment for insulin resistance (HOMA-IR), triglycerides and C-reactive protein levels were decreased. The decrease in these parameters was statistically significant for triglycerides (-22.3 ± 9.3 mg dl-1 : p = 0.03), C-reactive protein (-2.8 ± 0.5 mg dl-1 : p = 0.03), insulin (-7.4 ± 2.9 mUI L-1 : p = 0.03) and HOMA-IR (-2.4 ± 1.0: p = 0.02). Leptin levels were decreased in both genotypes groups after the hypocaloric diet, as well as the anthropometric parameters BMI, weight, waist circumference and fat mass. Resistin and adiponectin levels remained unchanged in both groups. CONCLUSIONS In the present study, we have detected a significant association between the T allele of this SNP and a better response of insulin resistance, triglycerides and C-reactive protein compared to non T allele carriers after weight loss with a high-fat hypocaloric diet and a Mediterranean diet.
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Affiliation(s)
- Daniel de Luis
- Center of Investigation of Endocrinology and Nutrition, Medicine School and Department of Endocrinology and Nutrition, Hospital Clinico Universitario, University of Valladolid, Valladolid, Spain
| | - Rocío Aller
- Center of Investigation of Endocrinology and Nutrition, Medicine School and Department of Endocrinology and Nutrition, Hospital Clinico Universitario, University of Valladolid, Valladolid, Spain
| | - Olatz Izaola
- Center of Investigation of Endocrinology and Nutrition, Medicine School and Department of Endocrinology and Nutrition, Hospital Clinico Universitario, University of Valladolid, Valladolid, Spain
| | - David Primo
- Center of Investigation of Endocrinology and Nutrition, Medicine School and Department of Endocrinology and Nutrition, Hospital Clinico Universitario, University of Valladolid, Valladolid, Spain
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20
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Lee KO, Lee KY, Lee CY, Kim JH, Kang J, Lee HY, Na SJ, Oh SH, Heo JH. High Serum Levels of Resistin is Associated With Acute Cerebral Infarction. Neurologist 2021; 27:41-45. [PMID: 34842580 PMCID: PMC8900991 DOI: 10.1097/nrl.0000000000000362] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
BACKGROUND The inflammatory process is involved in the pathogenesis of atherosclerosis and brain tissue injury following cerebral ischemia. Human resistin is a member of small cysteine-rich secreted proteins and has been implicated in inflammatory responses. This study investigated the association of serum resistin level with acute cerebral infarction (ACI). We also investigated its association with the short-term functional outcome. METHODS This study included 106 patients with ACI and 106 age-matched and sex-matched healthy control subjects. Serum resistin level was assessed by using enzyme-linked immunosorbent sandwich assay. The association of serum resistin levels with ACI was analyzed by logistic regression analysis. RESULTS The serum resistin level was significantly higher in patients with ACI than the control group [median (interquartile range), 35.7 ng/mL (13.0 to 70.5) ng/mL vs. 10.5 ng/ml (15.4 to 16.6), P<0.001]. Logistic regression analysis showed that serum resistin level was associated with an ACI (odds ratio=1.055, 95% confidence interval: 1.035-1.074, P<0.001). Among stroke subtypes, the serum resistin level was higher in the patients with large artery atherosclerosis than those with other subtypes (P=0.013). High resistin levels were also significantly associated with unfavorable functional outcome at discharge (odds ratio=1.043, 95% confidence interval: 1.024-1.063, P<0.001). CONCLUSIONS This study suggests the potential association of resistin with stroke and cerebral atherosclerosis. Increased serum resistin levels were also associated with early unfavorable neurological outcome.
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Affiliation(s)
- Kee Ook Lee
- Department of Neurology, CHA Bundang Medical Center, CHA University, Seongnam
- Myunggok Medical Research Institute
| | - Kyung-Yul Lee
- Department of Neurology, Yonsei University College of Medicine, Seoul, Korea
| | | | - Ji Hoon Kim
- Department of Neurology, Daejeon Sun Hospital, Daejeon
| | | | | | - Sang-Jun Na
- Neurology, Konyang University College of Medicine
| | - Seung-Hun Oh
- Department of Neurology, CHA Bundang Medical Center, CHA University, Seongnam
| | - Ji Hoe Heo
- Department of Neurology, Yonsei University College of Medicine, Seoul, Korea
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21
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Wu O, Hang Leng J, Zhang XY, Liu W, Zhang H, Yang FF, Li JJ, Zhang GZ, Lu X. The value of adiponectin-resistin (AR) index in newly diagnosed obesity hypertension: a case control study among Chinese adult. Clin Exp Hypertens 2021; 44:40-45. [PMID: 34636713 DOI: 10.1080/10641963.2021.1984500] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
OBJECTIVE To explore the role of adiponectin-resistin (AR) index as a better indicator of obesity-related hypertension. METHOD(S) This study continued a case control study that had finished recruiting 153 subjects divided as four characteristic groups. Fasting serum resistin levels (FSR) and Fasting serum adiponectin levels (FSA) were tested by ELISA. And, other related anthropometric clinical and metabolic data were collected. Analyzation on correlations between research index and differences between groups were done by SPSS. AR index's performance was also validated by the receiver operating characteristic (ROC) curves, the net reclassification improvement (NRI), and the integrated discrimination improvement (IDI). RESULT(S) The AR index was defined as 1+ log10(R0)-log10(A0). AUC of the AR index was 0.660 and NRI and IDI indicated AR index outperformed FSA alone. AR index statistically significantly negatively correlated with SB and DB and positively with ALB and SCR. AR index was statistically significantly different between the NH group and OH group and more specific than FSR alone as a biomarker of obesity-related hypertension. CONCLUSION(S) The AR index was more strongly associated with increased risk of obesity-related hypertension than the solely index of FSR or FSA and was useful for early diagnosis of obesity-related hypertension.
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Affiliation(s)
- Ou Wu
- Shulan International Medical College, Zhejiang Shuren University, Zhejiang, P.R. China
| | - Jian Hang Leng
- Department of Central Laboratory/Medical Examination Center of Hangzhou, The First People's Hospital of Hangzhou, Zhejiang, P.R. China
| | - Xing Yu Zhang
- Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Wei Liu
- Joinstar Biomedical Technology Co., LTD, Hangzhou, P.R. China
| | - Hu Zhang
- Department of Thoracic Surgery, Sir Run Run Shaw Hospital Affiliated with Medical College of Zhejiang University, Zhejiang, P.R. China
| | - Fen Fang Yang
- Department of Central Laboratory/Medical Examination Center of Hangzhou, The First People's Hospital of Hangzhou, Zhejiang, P.R. China
| | - Jia Jia Li
- Department of Central Laboratory, The First Affiliated Hospital of Anhui Medical University, Anhui, P.R. China
| | - Guo Zhong Zhang
- Hangzhou Center for Disease Control and Prevention, Zhejiang, P.R. China
| | - Xi Lu
- Hangzhou Vocational and Technical College, Zhejiang, P.R. China
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22
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Abdalla MMI. Salivary resistin level and its association with insulin resistance in obese individuals. World J Diabetes 2021; 12:1507-1517. [PMID: 34630903 PMCID: PMC8472494 DOI: 10.4239/wjd.v12.i9.1507] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2021] [Revised: 05/11/2021] [Accepted: 07/15/2021] [Indexed: 02/06/2023] Open
Abstract
The escalating global burden of type 2 diabetes mellitus necessitates the implementation of strategies that are both more reliable and faster in order to improve the early identification of insulin resistance (IR) in high-risk groups, including overweight and obese individuals. The use of salivary biomarkers offers a promising alternative to serum collection because it is safer, more comfortable, and less painful to obtain saliva samples. As obesity is the foremost contributory factor in IR development, the adipocytokines such as leptin, adiponectin, resistin, and visfatin secreted from the adipose tissue have been studied as potential reliable biomarkers for IR. Measurement of salivary adipokines as predictors for IR has attracted widespread attention because of the strong correlation between their blood and salivary concentrations. One of the adipokines that is closely related to IR is resistin. However, there are conflicting findings on resistin's potential role as an etiological link between obesity and IR and the reliability of measuring salivary resistin as a biomarker for IR. Hence this study reviewed the available evidence on the potential use of salivary resistin as a biomarker for IR in order to attempt to gain a better understanding of the role of resistin in the development of IR in obese individuals.
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23
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Taouis M, Benomar Y. Is resistin the master link between inflammation and inflammation-related chronic diseases? Mol Cell Endocrinol 2021; 533:111341. [PMID: 34082045 DOI: 10.1016/j.mce.2021.111341] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2021] [Revised: 05/25/2021] [Accepted: 05/28/2021] [Indexed: 01/07/2023]
Abstract
Resistin has been firstly discovered in mice and was identified as an adipose tissue-secreted hormone or adipokine linking obesity and insulin resistance. In humans, resistin has been characterized as a hormone expressed and secreted by Immune cells especially by macrophages, and was linked to many inflammatory responses including inflammation of adipose tissue due to macrophages' infiltration. Human and mouse resistin display sequence and structural similarities and also dissimilarities that could explain their different expression pattern. In mice, strong pieces of evidence clearly associated high resistin plasma levels to obesity and insulin resistance suggesting that resistin could play an important role in the onset and progression of obesity and insulin resistance via resistin-induced inflammation. In humans, the link between resistin and obesity/insulin resistance is still a matter of debate and needs more epidemiological studies. Also, resistin has been linked to other chronic diseases such as cardiovascular diseases and cancers where resistin has been proposed in many studies as a biological marker.
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Affiliation(s)
- Mohammed Taouis
- Molecular Neuroendocrinology of Food Intake (NMPA), UMR 9197, University of Paris-Saclay, Orsay, France; NMPA, Dept. Development, Evolution and Cell Signaling, Paris-Saclay Institute of Neurosciences (NeuroPSI) CNRS UMR 9197, Orsay, France.
| | - Yacir Benomar
- Molecular Neuroendocrinology of Food Intake (NMPA), UMR 9197, University of Paris-Saclay, Orsay, France; NMPA, Dept. Development, Evolution and Cell Signaling, Paris-Saclay Institute of Neurosciences (NeuroPSI) CNRS UMR 9197, Orsay, France
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24
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Nikanfar S, Oghbaei H, Rastgar Rezaei Y, Zarezadeh R, Jafari-Gharabaghlou D, Nejabati HR, Bahrami Z, Bleisinger N, Samadi N, Fattahi A, Nouri M, Dittrich R. Role of adipokines in the ovarian function: Oogenesis and steroidogenesis. J Steroid Biochem Mol Biol 2021; 209:105852. [PMID: 33610800 DOI: 10.1016/j.jsbmb.2021.105852] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2020] [Revised: 12/28/2020] [Accepted: 01/30/2021] [Indexed: 01/02/2023]
Abstract
Adipokines are mainly produced by adipose tissue; however, their expression has been reported in other organs including female reproductive tissues. Therefore, adipokines have opened new avenues of research in female fertility. In this regard, studies reported different roles for certain adipokines in ovarian function, although the role of other recently identified adipokines is still controversial. It seems that adipokines are essential for normal ovarian function and their abnormal levels could be associated with ovarian-related disorders. The objective of this study is to review the available information regarding the role of adipokines in ovarian functions including follicular development, oogenesis and steroidogenesis and also their involvement in ovary-related disorders.
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Affiliation(s)
- Saba Nikanfar
- Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Biochemistry and Clinical Laboratories, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Hajar Oghbaei
- Department of Physiology, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Yeganeh Rastgar Rezaei
- Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran; Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Reza Zarezadeh
- Department of Biochemistry and Clinical Laboratories, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Davoud Jafari-Gharabaghlou
- Department of Biochemistry and Clinical Laboratories, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Hamid Reza Nejabati
- Department of Biochemistry and Clinical Laboratories, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Zahra Bahrami
- Department of Reproductive Biology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Nathalie Bleisinger
- Department of Obstetrics and Gynecology, Erlangen University Hospital, Friedrich-Alexander University of Erlangen, Nürnberg, Erlangen, Germany
| | - Naser Samadi
- Department of Biochemistry and Clinical Laboratories, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Amir Fattahi
- Department of Reproductive Biology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Obstetrics and Gynecology, Erlangen University Hospital, Friedrich-Alexander University of Erlangen, Nürnberg, Erlangen, Germany; Women's Reproductive Health Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
| | - Mohammad Nouri
- Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Reproductive Biology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
| | - Ralf Dittrich
- Department of Obstetrics and Gynecology, Erlangen University Hospital, Friedrich-Alexander University of Erlangen, Nürnberg, Erlangen, Germany
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25
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Wu O, Leng JH, Yang FF, Zhang H, Zhang XY, Li JJ, Lu X. The paradox of the role of resistin in early-onset obesity hypertension: A comparative study among four Chinese adult subgroups. Clin Exp Hypertens 2021; 43:385-391. [PMID: 33749466 DOI: 10.1080/10641963.2021.1883049] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Objective: To explore the role of resistin in the onset and development of obesity-related hypertension.Methods: Resistin serum levels were tested by ELISA in 153 adult subjects among four characteristic Chinese adult physical examination groups. Waist circumference (WC), body mass index (BMI), systolic blood pressure (SB), diastolic blood pressure (DB), and other clinical laboratory data were collected. Following, correlations between research index and differences between groups were analyzed using SPSS.Results: Serum resistin levels statistically significantly negatively correlated with SB, DB and BMI, but statistically significantly positively correlated with serum creatinine (SCR) and serum albumin (ALB), even after adjustment for age and/or gender. The serum level of resistin in the normal healthy subject group (NH) was higher than in other groups.Conclusions: Resistin's role in the onset of obesity-related hypertension may be more important than what has been previously assumed. More pathway substances in the early onset of obesity-related hypertension should be tested.Abbreviations: WC, waist circumference; GGT, Gamma-glutamyltransferase; ALB, Albumin; ALT, Alanine aminotransferase; LDL, Low density lipoprotein cholesterol; TG, Triglyceride; HDLC, High density lipoprotein cholesterol; FA Fructosamine; SCR, serum creatinine; IB, Indirect bilirubin; ALP, Alkaline phosphatase; CB, Conjugated bilirubin; UREA, Urea; Ua, Uric acid; FBG, fasting blood glucose; TC, Total cholesterol; TB, Total bilirubin; TP, Total protein; TC/HDLC, TC/HDLC ratio; SB, systolic blood pressure; DB, diastolic blood pressure.
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Affiliation(s)
- Ou Wu
- Shulan International Medical College, Zhejiang Shuren University, Zhejiang, P.R. China.,Hangzhou Center for Disease Control and Prevention, Zhejiang, P.R. China
| | - Jian Hang Leng
- Department of Central Laboratory/Medical Examination Center of Hangzhou, The Frist People's Hospital of Hangzhou, Zhejiang, P.R. China
| | - Fen Fang Yang
- Department of Central Laboratory/Medical Examination Center of Hangzhou, The Frist People's Hospital of Hangzhou, Zhejiang, P.R. China
| | - Hu Zhang
- Department of Thoracic Surgery, Sir Run Run Shaw Hospital Affiliated with Medical College of Zhejiang University, Zhejiang, P.R. China
| | - Xing Yu Zhang
- Applied Biostatistics Laboratory, University of Michigan School of Nursing, Ann Arbor, USA
| | - Jia Jia Li
- Department of Central Laboratory, The First Affiliated Hospital of Anhui Medical University, Anhui, P.R. China
| | - Xi Lu
- Hangzhou Vocational and Technical College, Zhejiang, P.R. China
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26
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Rajesh Y, Sarkar D. Association of Adipose Tissue and Adipokines with Development of Obesity-Induced Liver Cancer. Int J Mol Sci 2021; 22:ijms22042163. [PMID: 33671547 PMCID: PMC7926723 DOI: 10.3390/ijms22042163] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2020] [Revised: 02/01/2021] [Accepted: 02/02/2021] [Indexed: 12/20/2022] Open
Abstract
Obesity is rapidly dispersing all around the world and is closely associated with a high risk of metabolic diseases such as insulin resistance, dyslipidemia, and nonalcoholic fatty liver disease (NAFLD), leading to carcinogenesis, especially hepatocellular carcinoma (HCC). It results from an imbalance between food intake and energy expenditure, leading to an excessive accumulation of adipose tissue (AT). Adipocytes play a substantial role in the tumor microenvironment through the secretion of several adipokines, affecting cancer progression, metastasis, and chemoresistance via diverse signaling pathways. AT is considered an endocrine organ owing to its ability to secrete adipokines, such as leptin, adiponectin, resistin, and a plethora of inflammatory cytokines, which modulate insulin sensitivity and trigger chronic low-grade inflammation in different organs. Even though the precise mechanisms are still unfolding, it is now established that the dysregulated secretion of adipokines by AT contributes to the development of obesity-related metabolic disorders. This review focuses on several obesity-associated adipokines and their impact on obesity-related metabolic diseases, subsequent metabolic complications, and progression to HCC, as well as their role as potential therapeutic targets. The field is rapidly developing, and further research is still required to fully understand the underlying mechanisms for the metabolic actions of adipokines and their role in obesity-associated HCC.
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Affiliation(s)
- Yetirajam Rajesh
- Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, VA 23298, USA;
| | - Devanand Sarkar
- Massey Cancer Center, Department of Human and Molecular Genetics, VCU Institute of Molecular Medicine (VIMM), Virginia Commonwealth University, Richmond, VA 23298, USA
- Correspondence: ; Tel.: +1-804-827-2339
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27
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Sato H, Funaki A, Kimura Y, Sumitomo M, Yoshida H, Okumura A, Fukata H, Hosoyama H, Kuroda M, Okawa T, Hisaka A, Ueno K. [Anti-diabetic effect of ethanol extract of Cyclolepis genistoides D. Don (Palo azul), made in Paraguay]. Nihon Yakurigaku Zasshi 2020; 155:202-208. [PMID: 32612029 DOI: 10.1254/fpj.20023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
Abstract
Extract of Cyclolepis genistoides D. Don (vernacular name Palo azul; Palo) are traditionally consumed in the Republic of Paraguay in South America for the treatment of diabetes and kidney disease, and is sold in Japan as dietary supplement. This study aimed to elucidate the mechanism of anti-diabetes activity of Palo, especially focused on insulin resistance. Palo promoted adipocytes differentiation and regulated adipokine profiles in 3T3-L1 adipocytes by modulation of PPARγ, a major regulator of adipose differentiation. Human adipocyte showed almost similar profile with 3T3-L1 against Palo treatment. Furthermore, Palo treatment (250 or 1000 mg/kg) was performed with C57BL/6J mice for 14 weeks, being fed high-fat-diet (HFD60) simultaneously. Palo 250 mg/kg exhibited a tendency to decrease subcutaneous adipose volume along with increase of PPARγ and its target, adiponectin mRNA expression. In addition, as the other insulin targeted cell, effect on muscle differentiation was examined. Palo increased differentiation of C2C12 mouse muscle myoblasts by increase of IGF-1, myogenin, and myosine heavy chain (MHC) as well as 5'-AMP-activated protein kinase (AMPK) activation. Palo subsequently promoted myotube formation under differentiation condition. From the above, it was clarified that Palo acts variously on the differentiation and maturation of both adipocytes and muscle cells, and from the viewpoint of the regulatory mechanism for adipocytes, PPARγ-inducing action was shown to be a mechanism that acts across species.
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Affiliation(s)
- Hiromi Sato
- Clinical Pharmacology and Pharmacometrics, Graduate School of Pharmaceutical Sciences, Chiba University
| | - Asami Funaki
- Clinical Pharmacology and Pharmacometrics, Graduate School of Pharmaceutical Sciences, Chiba University
| | - Yuki Kimura
- Clinical Pharmacology and Pharmacometrics, Graduate School of Pharmaceutical Sciences, Chiba University
| | - Mai Sumitomo
- Clinical Pharmacology and Pharmacometrics, Graduate School of Pharmaceutical Sciences, Chiba University
| | | | | | | | | | | | - Toya Okawa
- Clinical Pharmacology and Pharmacometrics, Graduate School of Pharmaceutical Sciences, Chiba University
| | - Akihiro Hisaka
- Clinical Pharmacology and Pharmacometrics, Graduate School of Pharmaceutical Sciences, Chiba University
| | - Koichi Ueno
- Center for Preventive Medical Science, Chiba University
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28
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Zorena K, Jachimowicz-Duda O, Ślęzak D, Robakowska M, Mrugacz M. Adipokines and Obesity. Potential Link to Metabolic Disorders and Chronic Complications. Int J Mol Sci 2020; 21:E3570. [PMID: 32443588 PMCID: PMC7278967 DOI: 10.3390/ijms21103570] [Citation(s) in RCA: 240] [Impact Index Per Article: 48.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2020] [Revised: 05/14/2020] [Accepted: 05/15/2020] [Indexed: 12/19/2022] Open
Abstract
The World Health Organization (WHO) has recognized obesity as one of the top ten threats to human health. It is estimated that the number of obese and overweight people worldwide exceeds the number of those who are undernourished. Obesity is not only a state of abnormally increased adipose tissue in the body, but also of increased release of biologically active adipokines. Adipokines released into the circulating blood, due to their specific receptors on the surface of target cells, act as classic hormones affecting the metabolism of tissues and organs. What is more, adipokines and cytokines may decrease the insulin sensitivity of tissues and induce inflammation and development of chronic complications. Certainly, it can be stated that in an era of a global obesity pandemic, adipokines may gain more and more importance as regards their use in the diagnostic evaluation and treatment of diseases. An extensive search for materials on the role of white, brown and perivascular fatty tissue and obesity-related metabolic and chronic complications was conducted online using PubMed, the Cochrane database and Embase.
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Affiliation(s)
- Katarzyna Zorena
- Department of Immunobiology and Environment Microbiology, Medical University of Gdańsk, Dębinki 7, 80-211 Gdańsk, Poland
| | - Olga Jachimowicz-Duda
- Independent Public Specialized Health Care Center in Lębork, Department of Internal Diseases, Węgrzynowicza 13, 84-300 Lębork, Poland;
| | - Daniel Ślęzak
- Department of Emergency Medicine, Faculty of Health Sciences, Medical University of Gdańsk, Smoluchowskiego 17, 80-214 Gdańsk, Poland;
| | - Marlena Robakowska
- Department of Public Health & Social Medicine, Faculty of Health Sciences, Medical University of Gdańsk, Al. Zwycięctwa 42a, 80-210 Gdańsk, Poland;
| | - Małgorzata Mrugacz
- Department of Ophthalmology and Eye Rehabilitation, Medical University of Bialystok, Kilinskiego 1, 15-089 Białystok, Poland;
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29
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Psoriasis and Psoriatic Arthritis Cardiovascular Disease Endotypes Identified by Red Blood Cell Distribution Width and Mean Platelet Volume. J Clin Med 2020; 9:jcm9010186. [PMID: 31936662 PMCID: PMC7019311 DOI: 10.3390/jcm9010186] [Citation(s) in RCA: 47] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2019] [Revised: 12/27/2019] [Accepted: 01/03/2020] [Indexed: 12/12/2022] Open
Abstract
In a subset of psoriasis (PsO) and psoriatic arthritis (PsA) patients, the skin and/or joint lesions appear to generate biologically significant systemic inflammation. Red cell distribution width (RDW) and mean platelet volume (MPV) are readily available clinical tests that reflect responses of the bone marrow and/or plasma thrombogenicity (e.g., inflammation), and can be markers for major adverse cardiac events (MACE). We aimed to evaluate if RDW and MPV may be employed as inexpensive, routinely obtained biomarkers in predicting myocardial infarction (MI), atrial fibrillation (AF), and chronic heart failure (CHF) in psoriatic and psoriatic arthritis patients. The study was divided into two parts: (a) case control study employing big data (Explorys) to assess MPV and RDW in psoriasis, psoriatic arthritis and control cohorts; (b) a clinical observational study to validate the predictive value of RDW and to evaluate RDW response to anti-psoriatic therapies. We used Explorys, an aggregate electronic database, to identify psoriatic patients with available MPV and RDW data and compared them to gender and age matched controls. The incidence of myocardial infarction (MI), atrial fibrillation (AF), and chronic heart failure (CHF) was highest among patients with both elevated RDW and MPV, followed by patients with high RDW and normal MPV. RDW elevation among PsA patients was associated with an increased risk of MI, AF, and CHF. In a local clinical cohort, high RDWs were concentrated in a subset of patients who also had elevated circulating resistin levels. Among a small subset of participants who were treated with various systemic and biologic therapies, and observed over a year, and in whom RDW was elevated at baseline, a sustained response to therapy was associated with a decrease in RDW. RDW and MPV, tests commonly contained within routine complete blood count (CBC), may be a cost-effective manner to identify PsO and PsA patients at increased risk of MACE.
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30
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Chiang H, Lee J, Huang H, Huang H, Liu H, Huang C. Delayed intervention with a novel SGLT2 inhibitor NGI001 suppresses diet-induced metabolic dysfunction and non-alcoholic fatty liver disease in mice. Br J Pharmacol 2020; 177:239-253. [PMID: 31497874 PMCID: PMC6989948 DOI: 10.1111/bph.14859] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2019] [Revised: 08/26/2019] [Accepted: 08/29/2019] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND AND PURPOSE Non-alcoholic fatty liver disease (NAFLD), including non-alcoholic steatohepatitis, is closely related to metabolic diseases such as obesity and diabetes. Despite an accumulating number of studies, no pharmacotherapy that targets NAFLD has received general approval for clinical use. EXPERIMENTAL APPROACH Inhibition of the sodium-glucose cotransporter 2 (SGLT2) is a promising approach to treat diabetes, obesity, and associated metabolic disorders. In this study, we investigated the effect of a novel SGLT2 inhibitor, NGI001, on NAFLD and obesity-associated metabolic symptoms in high-fat diet (HFD)-induced obese mice. KEY RESULTS Delayed intervention with NGI001 protected against body weight gain, hyperglycaemia, hyperlipidaemia, and hyperinsulinaemia, compared with HFD alone. Adipocyte hypertrophy was prevented by administering NGI001. NGI001 inhibited impaired glucose metabolism and regulated the secretion of adipokines associated with insulin resistance. In addition, NGI001 supplementation suppressed hepatic lipid accumulation and inflammation but had little effect on kidney function. In-depth investigations showed that NGI001 ameliorated fat deposition and increased AMPK phosphorylation, resulting in phosphorylation of its major downstream target, acetyl-CoA carboxylase, in human hepatocyte HuS-E/2 cells. This cascade ultimately led to the down-regulation of downstream fatty acid synthesis-related molecules and the up-regulation of downstream β oxidation-associated molecules. Surprisingly, NGI001 decreased gene and protein expression of SGLT1 and SGLT2 and glucose uptake in oleic acid-treated HuS-E/2 cells. CONCLUSION AND IMPLICATIONS Our findings suggest the novel SGLT2 inhibitor, NGI001 has therapeutic potential to attenuate or delay the onset of diet-induced metabolic diseases and NAFLD.
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Affiliation(s)
- Hao Chiang
- Department of Biotechnology and Laboratory Science in MedicineNational Yang‐Ming UniversityTaipeiTaiwan
| | - Jinq‐Chyi Lee
- Institute of Biotechnology and Pharmaceutical ResearchNational Health Research InstitutesMiaoli CountyTaiwan
| | - Hsiu‐Chen Huang
- Department of Applied ScienceNational Tsing Hua University, South CampusHsinchuTaiwan
| | - Hsing Huang
- Department of Biotechnology and Laboratory Science in MedicineNational Yang‐Ming UniversityTaipeiTaiwan
| | - Hui‐Kang Liu
- National Research Institute of Chinese MedicineMinistry of Health and WelfareTaipeiTaiwan
- Ph.D. Program in Clinical Drug Development of Chinese Herbal MedicineTaipei Medical UniversityTaipeiTaiwan
| | - Cheng Huang
- Department of Biotechnology and Laboratory Science in MedicineNational Yang‐Ming UniversityTaipeiTaiwan
- Department of Earth and Life SciencesUniversity of TaipeiTaipeiTaiwan
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31
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de Gennaro G, Palla G, Battini L, Simoncini T, Del Prato S, Bertolotto A, Bianchi C. The role of adipokines in the pathogenesis of gestational diabetes mellitus. Gynecol Endocrinol 2019; 35:737-751. [PMID: 30990092 DOI: 10.1080/09513590.2019.1597346] [Citation(s) in RCA: 38] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/13/2023] Open
Abstract
Gestational diabetes mellitus (GDM) is a complex condition whose physiopathology to date has not been completely clarified. Two major metabolic disorders, insulin resistance and β-cells dysfunction, play currently major role in pathogenesis of GDM. These elements are influenced by the amount of adipose tissue present before and/or during the pregnancy. Consequently, adipokines (adiponectin (APN), leptin (LPT), adipocyte fatty acid-binding protein, resistin, visfatin, omentin, vaspin, apelin, chemerin) secreted by adipose tissue, may contribute directly and/or indirectly, through the enhancement of chronic inflammation, aggravating insulin resistance and promoting GDM onset. This review aims to outline the potential physiopathological and prognostic role in GDM of adipokines, mainly APN and LPT.
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Affiliation(s)
- G de Gennaro
- a Department of Clinical and Experimental Medicine, University of Pisa , Pisa , Italy
| | - G Palla
- a Department of Clinical and Experimental Medicine, University of Pisa , Pisa , Italy
| | - L Battini
- b Maternal-Infant Department, University Hospital of Pisa , Pisa , Italy
| | - T Simoncini
- a Department of Clinical and Experimental Medicine, University of Pisa , Pisa , Italy
| | - S Del Prato
- a Department of Clinical and Experimental Medicine, University of Pisa , Pisa , Italy
| | - A Bertolotto
- c Department of Medicine, University Hospital of Pisa , Pisa , Italy
| | - C Bianchi
- c Department of Medicine, University Hospital of Pisa , Pisa , Italy
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32
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Takashima S, Nishii N, Kobatake Y, Kiyosue M, Kimura S, Kitagawa H. Concentrations of leptin, adiponectin, and resistin in the serum of obese cats during weight loss. J Vet Med Sci 2019; 81:1294-1300. [PMID: 31366817 PMCID: PMC6785622 DOI: 10.1292/jvms.19-0091] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023] Open
Abstract
We monitored changes in serum leptin, adiponectin, and resistin concentrations in obese cats during weight loss. Six naturally developed obese cats were fed low-fat, high-fiber dry food
during a 9-week experimental period. Serum leptin, adiponectin, and resistin concentrations were measured at week 0, 4, 8, and 9. Body weight became significantly lower week 4 onward than
that at week 0 (P<0.05 or 0.01). At week 9, serum leptin concentrations were significantly lower than those at week 0 (P<0.05). Contrarily, serum
adiponectin and resistin concentrations did not significantly differ within the 9 weeks. While serum leptin levels were strongly positively correlated with body weight
(r=0.923, P<0.001), serum adiponectin levels were moderately negatively correlated with it (r=−0.529, P<0.01), with
serum resistin having a no correlation with body weight. Serum leptin levels might be more closely related with pathogenesis of adiposity than serum adiponectin or resistin in cats.
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Affiliation(s)
- Satoshi Takashima
- Joint Department of Veterinary Medicine, Faculty of Applied Biological Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan
| | - Naohito Nishii
- Joint Department of Veterinary Medicine, Faculty of Applied Biological Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan
| | - Yui Kobatake
- Joint Department of Veterinary Medicine, Faculty of Applied Biological Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan
| | - Masaharu Kiyosue
- Nisshin Pet Food Inc., 1-25 Kanda Nishiki-cho, Chiyoda-ku, Tokyo 101-8441, Japan
| | - Seiji Kimura
- Nisshin Pet Food Inc., 1-25 Kanda Nishiki-cho, Chiyoda-ku, Tokyo 101-8441, Japan
| | - Hitoshi Kitagawa
- Department of Veterinary Medicine, Faculty of Veterinary Medicine, Okayama University of Science, 1-3 Ikoi-no-oka, Imabari, Ehime 794-8555, Japan
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Emamalipour M, Seidi K, Jahanban‐Esfahlan A, Jahanban‐Esfahlan R. Implications of resistin in type 2 diabetes mellitus and coronary artery disease: Impairing insulin function and inducing pro‐inflammatory cytokines. J Cell Physiol 2019; 234:21758-21769. [DOI: 10.1002/jcp.28913] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2019] [Revised: 05/13/2019] [Accepted: 05/20/2019] [Indexed: 12/20/2022]
Affiliation(s)
- Melissa Emamalipour
- Department of Medical Biotechnology Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences Tabriz Iran
- Student Research Committee, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences Tabriz Iran
| | - Khaled Seidi
- Department of Medical Biotechnology Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences Tabriz Iran
- Student Research Committee, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences Tabriz Iran
| | - Ali Jahanban‐Esfahlan
- Department of Medical Biotechnology Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences Tabriz Iran
- Student Research Committee, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences Tabriz Iran
| | - Rana Jahanban‐Esfahlan
- Department of Medical Biotechnology Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences Tabriz Iran
- Student Research Committee, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences Tabriz Iran
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Luo J, Liu H, Zheng X, Lin B, Ye Q, Deng Y, Wu L. Inhibitory Effect of Apelin on Cardiomyocyte Hypertrophy induced by Resistin in H9c2 Cells. INT J PHARMACOL 2019. [DOI: 10.3923/ijp.2019.311.317] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
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Justice AE, Chittoor G, Blanco E, Graff M, Wang Y, Albala C, Santos JL, Angel B, Lozoff B, Voruganti VS, North KE, Gahagan S. Genetic determinants of BMI from early childhood to adolescence: the Santiago Longitudinal Study. Pediatr Obes 2019; 14:e12479. [PMID: 30515969 PMCID: PMC6696926 DOI: 10.1111/ijpo.12479] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2018] [Revised: 08/24/2018] [Accepted: 09/13/2018] [Indexed: 01/05/2023]
Abstract
BACKGROUND While the genetic contribution to obesity is well established, few studies have examined how genetic variants influence standardized body mass index Z-score (BMIz) in Hispanics/Latinos, especially across childhood and adolescence. OBJECTIVES We estimated the effect of established BMIz loci in Chilean children of the Santiago Longitudinal Study (SLS). METHODS We examined associations with BMIz at age 10 for 15 loci previously identified in European children. For significant loci, we performed association analyses at ages 5 and 16 years, for which we have smaller sample sizes. We tested associations of unweighted genetic risk scores (GRSs) for previously identified tag variants (GRS_EUR) and from the most significant variants in SLS at each locus (GRS_SLS). RESULTS We generalized five variants at age 10 (P < 0.05 and directionally consistent), including rs543874 that reached Bonferroni-corrected significance. The effect on BMIz was greatest at age 10 for all significant loci, except FTO, which exhibited an increase in effect from ages 5 to 16. Both GRSs were associated with BMIz (P < 0.0001), but GRS_SLS explained a much greater proportion of the variation (13.63%). CONCLUSION Our results underscore the importance of conducting genetic investigations across life stages and selecting ancestry appropriate tag variants in future studies for disease prediction and clinical evaluation.
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Affiliation(s)
- Anne E. Justice
- Biomedical and Translational Informatics, Geisinger, Danville, PA, USA,Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel
Hill, Chapel Hill, NC, USA
| | - Geetha Chittoor
- Biomedical and Translational Informatics, Geisinger, Danville, PA, USA,Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel
Hill, Chapel Hill, NC, USA
| | - Estela Blanco
- Division of Academic General Pediatrics, Child Development and Community Health at the Center for Community
Health, University of California at San Diego, San Diego, CA, USA
| | - Mariaelisa Graff
- Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel
Hill, Chapel Hill, NC, USA
| | - Yujie Wang
- Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel
Hill, Chapel Hill, NC, USA
| | - Cecilia Albala
- Department of Public Health Nutrition, Institute of Nutrition and Food Technology (INTA), University of
Chile, Santiago, Chile
| | - José L. Santos
- Department of Nutrition, Diabetes and Metabolism, School of Medicine, Pontificia Universidad Católica
de Chile, Santiago, Chile
| | - Bárbara Angel
- Department of Public Health Nutrition, Institute of Nutrition and Food Technology (INTA), University of
Chile, Santiago, Chile
| | - Betsy Lozoff
- Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, MI, USA
| | - V. Saroja Voruganti
- Department of Nutrition and Nutrition Research Institute, University of North Carolina at Chapel Hill,
Kannapolis NC 28081, USA
| | - Kari E. North
- Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel
Hill, Chapel Hill, NC, USA
| | - Sheila Gahagan
- Division of Academic General Pediatrics, Child Development and Community Health at the Center for Community
Health, University of California at San Diego, San Diego, CA, USA
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Acquarone E, Monacelli F, Borghi R, Nencioni A, Odetti P. Resistin: A reappraisal. Mech Ageing Dev 2019; 178:46-63. [DOI: 10.1016/j.mad.2019.01.004] [Citation(s) in RCA: 122] [Impact Index Per Article: 20.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2018] [Revised: 12/28/2018] [Accepted: 01/11/2019] [Indexed: 02/07/2023]
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Contreras-Duarte S, Carvajal L, Fuenzalida B, Cantin C, Sobrevia L, Leiva A. Maternal Dyslipidaemia in Pregnancy with Gestational Diabetes Mellitus: Possible Impact on Foetoplacental Vascular Function and Lipoproteins in the Neonatal Circulation. Curr Vasc Pharmacol 2018; 17:52-71. [DOI: 10.2174/1570161115666171116154247] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2017] [Revised: 10/30/2017] [Accepted: 11/04/2017] [Indexed: 01/06/2023]
Abstract
Dyslipidaemia occurs in pregnancy to secure foetal development. The mother shows a physiological
increase in plasma total cholesterol and Triglycerides (TG) as pregnancy progresses (i.e. maternal
physiological dyslipidaemia in pregnancy). However, in some women pregnancy-associated dyslipidaemia
exceeds this physiological adaptation. The consequences of this condition on the developing
fetus include endothelial dysfunction of the foetoplacental vasculature and development of foetal aortic
atherosclerosis. Gestational Diabetes Mellitus (GDM) associates with abnormal function of the foetoplacental
vasculature due to foetal hyperglycaemia and hyperinsulinaemia, and associates with development
of cardiovascular disease in adulthood. Supraphysiological dyslipidaemia is also detected in
GDM pregnancies. Although there are several studies showing the alteration in the maternal and neonatal
lipid profile in GDM pregnancies, there are no studies addressing the effect of dyslipidaemia in the
maternal and foetal vasculature. The literature reviewed suggests that dyslipidaemia in GDM pregnancy
should be an additional factor contributing to worsen GDM-associated endothelial dysfunction by altering
signalling pathways involving nitric oxide bioavailability and neonatal lipoproteins.
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Affiliation(s)
- Susana Contreras-Duarte
- Cellular and Molecular Physiology Laboratory (CMPL), Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontifical Catholic University of Chile, Santiago 8330024, Chile
| | - Lorena Carvajal
- Cellular and Molecular Physiology Laboratory (CMPL), Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontifical Catholic University of Chile, Santiago 8330024, Chile
| | - Bárbara Fuenzalida
- Cellular and Molecular Physiology Laboratory (CMPL), Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontifical Catholic University of Chile, Santiago 8330024, Chile
| | - Claudette Cantin
- Cellular and Molecular Physiology Laboratory (CMPL), Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontifical Catholic University of Chile, Santiago 8330024, Chile
| | - Luis Sobrevia
- Cellular and Molecular Physiology Laboratory (CMPL), Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontifical Catholic University of Chile, Santiago 8330024, Chile
| | - Andrea Leiva
- Cellular and Molecular Physiology Laboratory (CMPL), Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontifical Catholic University of Chile, Santiago 8330024, Chile
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Alipoor E, Mohammad Hosseinzadeh F, Hosseinzadeh-Attar MJ. Adipokines in critical illness: A review of the evidence and knowledge gaps. Biomed Pharmacother 2018; 108:1739-1750. [PMID: 30372877 DOI: 10.1016/j.biopha.2018.09.165] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2018] [Revised: 09/27/2018] [Accepted: 09/28/2018] [Indexed: 12/28/2022] Open
Abstract
Adipose tissue products or adipokines play a major role in chronic endocrine and metabolic disorders; however, little is known about critical conditions. In this article, the experimental and clinical evidence of alterations of adipokines, adiponectin, leptin, resistin, visfatin, asymmetric dimethylarginine (ADMA), and ghrelin in critical illness, their potential metabolic, diagnostic, and prognostic value, and the gaps in the field have been reviewed. The results showed considerable changes in the concentration of the adipokines; while the impact of adipokines on metabolic disorders such as insulin resistance and inflammation has not been well documented in critically ill patients. There is no consensus about the circulatory and functional changes of leptin and adiponectin. However, it seems that lower concentrations of adiponectin at admission with gradual consequent increase might be a useful pattern in determining better outcomes of critical illness. Some evidence has suggested the adverse effects of elevated resistin concentration, potential prognostic importance of visfatin, and therapeutic value of ghrelin. High ADMA levels and low arginine:ADMA ratio were also proposed as predictors of ICU mortality and morbidities. However, there is no consensus on these findings. Although primary data indicated the role of adipokines in critical illness, further studies are required to clarify whether the reason of these changes is pathophysiological or compensatory. The relationship of pathophysiological background, disease severity, baseline nutritional status and nutrition support during hospitalization, and variations in body fat percentage and distribution with adipokines, as well as the potential prognostic or therapeutic role of these peptides should be further investigated in critically ill patients.
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Affiliation(s)
- Elham Alipoor
- Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran, Iran; Department of Clinical Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
| | - Fatemeh Mohammad Hosseinzadeh
- Department of Clinical Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Javad Hosseinzadeh-Attar
- Department of Clinical Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran; Centre of Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide, Adelaide, Australia.
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Liu X, Zheng X, Su X, Tian W, Hu Y, Zhang Z. Plasma Resistin Levels in Patients with Acute Aortic Dissection: A Propensity Score-Matched Observational Case-Control Study. Med Sci Monit 2018; 24:6431-6437. [PMID: 30212440 PMCID: PMC6149239 DOI: 10.12659/msm.909469] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023] Open
Abstract
Background The aim of this observational case-control study was to compare the levels of plasma resistin between patients with acute aortic dissection and matched controls, and to use propensity score matching (PSM) to reduce case selection bias and clinical confounders. Material/Methods With the use of PSM, this study included 43 pairs of patients with acute aortic dissection (type-A and type-B dissection) and matched controls. Plasma resistin levels and other laboratory parameters were compared between the two groups, including white blood cell (WBC) count, glucose, high sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and D-dimer. The correlations between resistin and other laboratory parameters were evaluated in patients with acute aortic dissection. Results Following PSM adjustment for clinical variables, including age, sex, body mass index, smoking, alcohol drinking, hypertension, diabetes mellitus, coronary heart disease and stroke, plasma resistin levels were significantly increased in patients with acute aortic dissection when compared with controls (35.2±13.8 vs. 18.4±9.1 ng/ml) (p<0.001). WBC counts, and levels of glucose, hs-CRP, IL-6, TNF-α and D-dimer were also significantly increased in the patients with aortic dissection compared with the control group. After adjustment for these variables, the association between plasma resistin levels and acute aortic dissection remained significant (OR, 1.114; 95% CI, 1.036–1.224) (p<0.001). Plasma resistin levels was positively correlated with WBC count (r=0.368, p=0.015), hs-CRP (r=0.359, p=0.022), IL-6 (r=0.306, p=0.046) and TNF-α levels (r=0.315, p=0.040) in patients with acute aortic dissection. Conclusions Acute aortic dissection is associated with elevated levels of plasma resistin and other pro-inflammatory cytokines. Plasma resistin levels is positively associated with other pro-inflammatory cytokines in acute aortic dissection.
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Affiliation(s)
- Xintian Liu
- Department of Cardiology, Wuhan Asia Heart Hospital, Wuhan University of Science and Technology, Wuhan, Hubei, China (mainland)
| | - Xuan Zheng
- Laboratory of Molecular Cardiology, Wuhan Asia Heart Hospital, Wuhan University of Science and Technology, Wuhan, Hubei, China (mainland)
| | - Xi Su
- Department of Cardiology, Wuhan Asia Heart Hospital, Wuhan University of Science and Technology, Wuhan, Hubei, China (mainland)
| | - Wei Tian
- Department of Cardiology, Wuhan Asia Heart Hospital, Wuhan University of Science and Technology, Wuhan, Hubei, China (mainland)
| | - Yuanping Hu
- Laboratory of Molecular Cardiology, Wuhan Asia Heart Hospital, Wuhan University of Science and Technology, Wuhan, Hubei, China (mainland)
| | - Zhiping Zhang
- Department of Cardiology, Wuhan Asia Heart Hospital, Wuhan University of Science and Technology, Wuhan, Hubei, China (mainland)
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Modulation of Glucose Metabolism in Hippocampal Neurons by Adiponectin and Resistin. Mol Neurobiol 2018; 56:3024-3037. [PMID: 30076527 DOI: 10.1007/s12035-018-1271-x] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2018] [Accepted: 07/19/2018] [Indexed: 12/20/2022]
Abstract
Obese individuals exhibit altered circulating levels of adipokines, the proteins secreted by adipose tissue to mediate tissue cross-talk and regulate appetite and energy expenditure. The effect of adipokines on neuronal glucose metabolism, however, remains largely unknown. Two adipokines produced in adipose tissue, adiponectin and resistin, can gain access to the central nervous system (CNS), and their levels in the cerebrospinal fluid (CSF) are altered in obesity. We hypothesized that dysregulated adipokines in the CNS may underlie the reported link between obesity and higher risk of neurological disorders like Alzheimer's disease (AD), by affecting glucose metabolism in hippocampal neurons. Using cultured primary rat hippocampal neurons and mouse hippocampus slices, we show that recombinant adiponectin and resistin, at a concentration found in the CSF, have opposing effects on glucose metabolism. Adiponectin enhanced glucose uptake, glycolytic rate, and ATP production through an AMP-activated protein kinase (AMPK)-dependent mechanism; inhibiting AMPK abrogated the effects of adiponectin on glucose uptake and utilization. In contrast, resistin reduced glucose uptake, glycolytic rate, and ATP production, in part, by inhibiting hexokinase (HK) activity in hippocampal neurons. These data suggest that altered CNS levels of adipokines in the context of obesity may impact glucose metabolism in hippocampal neurons, brain region involved in learning and memory functions.
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Stine JG, Wang J, Cornella SL, Behm BW, Henry Z, Shah NL, Caldwell SH, Northup PG. Treatment of Type-1 Hepatorenal Syndrome with Pentoxifylline: A Randomized Placebo Controlled Clinical Trial. Ann Hepatol 2018; 17:300-306. [PMID: 29469046 PMCID: PMC7485043 DOI: 10.5604/01.3001.0010.8660] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
INTRODUCTION Type-1 hepatorenal syndrome (HRS-1) portends a poor prognosis in patients with cirrhosis. Currently available medical therapies are largely ineffective, save for liver transplantation. We aimed to determine if pentoxifylline (PTX) therapy in addition to the standard of care of volume expansion with albumin and vasoconstriction with midodrine and octreotide (AMO) is safe and efficacious compared to AMO in HRS-1 treatment. MATERIAL AND METHODS Hospitalized subjects with decompensated cirrhosis and HRS-1 were enrolled. PTX or placebo was administered with AMO therapy for up to 14 days. The primary endpoint was HRS-1 resolution (serum creatinine ≤ 1.5 g/dL for > 24 h). Secondary endpoints were change in creatinine and MELD score, partial treatment response, 30-and 180-day overall and transplant free survival. RESULTS Twelve subjects with mean age 58.9 ± 6.2 years were enrolled and randomized. Mean MELD score was 26.5 ± 7.4 and 58.3% were male. Overall cohort 30- and 180-day survival was 58.3% and 33.3% respectively. Two subjects underwent liver transplantation. HRS-1 resolution (16.7% vs. 16.7%, p = 1.000), partial treatment response (33.3% vs. 16.7%, p = 0.505), change in creatinine (+0.48 g/dL, 95% CI -0.49-1.46 vs. +0.03 g/dL, 95% CI -0.64- 0.70, p = 0.427), 30-day survival (66.6% vs. 50.0%, p = 0.558) and 180-day survival (50.0% vs. 16.7%, p = 0.221) were similar between the two groups. Serious adverse events necessitating treatment discontinuation were rare (n = 1, PTX). DISCUSSION The addition of PTX to AMO in the treatment of HRS-1 is safe when compared to the current standard of care. Future large-scale prospective study to validate the efficacy of this treatment seems warranted.
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Affiliation(s)
- Jonathan G. Stine
- Division of Gastroenterology & Hepatology, Department of Medicine, University of Virginia, Charlottesville, VA, United States
| | - Jennifer Wang
- Department of Medicine, University of Virginia, Charlottesville, VA, United States
| | - Scott L. Cornella
- Division of Gastroenterology & Hepatology, Department of Medicine, University of Virginia, Charlottesville, VA, United States
| | - Brian W. Behm
- Division of Gastroenterology & Hepatology, Department of Medicine, University of Virginia, Charlottesville, VA, United States
| | - Zachary Henry
- Division of Gastroenterology & Hepatology, Department of Medicine, University of Virginia, Charlottesville, VA, United States
| | - Neeral L. Shah
- Division of Gastroenterology & Hepatology, Department of Medicine, University of Virginia, Charlottesville, VA, United States
| | - Stephen H. Caldwell
- Division of Gastroenterology & Hepatology, Department of Medicine, University of Virginia, Charlottesville, VA, United States
| | - Patrick G. Northup
- Division of Gastroenterology & Hepatology, Department of Medicine, University of Virginia, Charlottesville, VA, United States
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Sarmento-Cabral A, L-López F, Luque RM. Adipokines and Their Receptors Are Widely Expressed and Distinctly Regulated by the Metabolic Environment in the Prostate of Male Mice: Direct Role Under Normal and Tumoral Conditions. Endocrinology 2017; 158:3540-3552. [PMID: 28938461 DOI: 10.1210/en.2017-00370] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2017] [Accepted: 08/03/2017] [Indexed: 12/15/2022]
Abstract
Adipose tissue-derived adipokines (i.e., leptin/adiponectin/resistin) play important roles in the regulation of several pathophysiologic processes through the activation of specific receptors. However, although adipokines and their receptors are widely distributed in many tissues and exhibit a clear modulation according to particular metabolic conditions (e.g., obesity and/or fasting), their expression, regulation, and putative action on normal prostate glands (PGs; a hormone-dependent organ tightly regulated by the endocrine-metabolic milieu) are still to be defined. Different in vivo/in vitro models were used to comprehensively characterize the expression pattern and actions of different adipokine systems (i.e., leptin/adiponectin/resistin/receptors) in mouse PGs. Adiponectin, resistin, and adiponectin receptors (1 and 2) and leptin receptor are coexpressed at different levels in PG cells, wherein they are finely regulated under fasting and/or obesity conditions. Furthermore, treatment with different adipokines exerted both homologous and heterologous regulation of specific adipokines/receptor-synthesis and altered the expression of key proliferation and oncogenesis markers (i.e., Ki67/c-Myc/p53) in mouse PG cell cultures, wherein some of these actions might be elicited through extracellular signal-regulated kinase (ERK) activation. Moreover, treatment with leptin, adiponectin, and resistin differentially regulated key functional parameters [i.e., proliferation and migration capacity and/or prostate-specific antigen (PSA) secretion] in human normal and/or tumoral prostate cell lines. Altogether, our data show that various adipokine and receptor systems are differentially expressed in normal PG cells; that their expression is under a complex ligand- and receptor-selective regulation under extreme metabolic conditions; and that they mediate distinctive and common direct actions in normal and tumoral PG cells (i.e., homologous and heterologous regulation of ligand and receptor synthesis, ERK signaling activation, modulation of proliferation markers, proliferation and migration capacity, and PSA secretion), suggesting a relevant role of these systems in the regulation of PG pathophysiology.
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Affiliation(s)
- André Sarmento-Cabral
- Maimonides Institute of Biomedical Research of Cordoba, 14004 Cordoba, Spain
- Reina Sofía University Hospital, 14004 Cordoba, Spain
- Department of Cell Biology, Physiology and Immunology, University of Cordoba, 14004 Cordoba, Spain
- CIBER Physiopathology of Obesity and Nutrition, 14004 Cordoba, Spain
- Internacional Campus of Excellence on Agrifood, 14004 Cordoba, Spain
| | - Fernando L-López
- Maimonides Institute of Biomedical Research of Cordoba, 14004 Cordoba, Spain
- Reina Sofía University Hospital, 14004 Cordoba, Spain
- Department of Cell Biology, Physiology and Immunology, University of Cordoba, 14004 Cordoba, Spain
- CIBER Physiopathology of Obesity and Nutrition, 14004 Cordoba, Spain
- Internacional Campus of Excellence on Agrifood, 14004 Cordoba, Spain
| | - Raúl M Luque
- Maimonides Institute of Biomedical Research of Cordoba, 14004 Cordoba, Spain
- Reina Sofía University Hospital, 14004 Cordoba, Spain
- Department of Cell Biology, Physiology and Immunology, University of Cordoba, 14004 Cordoba, Spain
- CIBER Physiopathology of Obesity and Nutrition, 14004 Cordoba, Spain
- Internacional Campus of Excellence on Agrifood, 14004 Cordoba, Spain
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Hajavi J, Momtazi AA, Johnston TP, Banach M, Majeed M, Sahebkar A. Curcumin: A Naturally Occurring Modulator of Adipokines in Diabetes. J Cell Biochem 2017; 118:4170-4182. [DOI: 10.1002/jcb.26121] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2017] [Accepted: 05/08/2017] [Indexed: 01/30/2023]
Affiliation(s)
- Jafar Hajavi
- Immunology Research CenterMashhad University of Medical SciencesMashhadIran
| | - Amir Abbas Momtazi
- Student Research Committee, Nanotechnology Research CenterDepartment of Medical Biotechnology, School of Medicine, Mashhad University of Medical SciencesMashhadIran
| | - Thomas P. Johnston
- Division of Pharmaceutical Sciences, School of PharmacyUniversity of Missouri‐Kansas CityKansas CityMissouri
| | - Maciej Banach
- Department of Hypertension, WAM University Hospital in LodzMedical University of LodzZeromskiego 113LodzPoland
| | | | - Amirhossein Sahebkar
- Biotechnology Research CenterMashhad University of Medical SciencesMashhad9177948564Iran
- Neurogenic Inflammation Research CenterMashhad University of Medical SciencesMashhadIran
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Kwon EY, Lee J, Kim YJ, Do A, Choi JY, Cho SJ, Jung UJ, Lee MK, Park YB, Choi MS. Seabuckthorn Leaves Extract and Flavonoid Glycosides Extract from Seabuckthorn Leaves Ameliorates Adiposity, Hepatic Steatosis, Insulin Resistance, and Inflammation in Diet-Induced Obesity. Nutrients 2017; 9:569. [PMID: 28574484 PMCID: PMC5490548 DOI: 10.3390/nu9060569] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2017] [Revised: 05/26/2017] [Accepted: 05/31/2017] [Indexed: 12/31/2022] Open
Abstract
The aim of the current study was to elucidate the effect of seabuckthorn leaves (SL) extract and flavonoid glycosides extract from seabuckthorn leaves (SLG) on diet-induced obesity and related metabolic disturbances, and additionally, to identify whether flavonoid glycosides and other components in SL can exert a possible interaction for the prevention of metabolic diseases by comparing the effect of SL and SLG. C57BL/6J mice were fed a normal diet (ND, AIN-93G purified diet), high-fat diet (HFD, 60 kcal% fat), HFD + 1.8% (w/w) SL (SL), and HFD + 0.04% (w/w) SLG (SLG) for 12 weeks. In high fat-fed mice, SL and SLG decreased the adiposity by suppressing lipogenesis in adipose tissue, while increasing the energy expenditure. SL and SLG also improved hepatic steatosis by suppressing hepatic lipogenesis and lipid absorption, whilst also enhancing hepatic fatty acid oxidation, which may be linked to the improvement in dyslipidemia. Moreover, SL and SLG improved insulin sensitivity by suppressing the levels of plasma GIP that were modulated by secreted resistin and pro-inflammatory cytokine, and hepatic glucogenic enzyme activities. SL, especially its flavonoid glycosides (SLG), can protect against the deleterious effects of diet-induced obesity (DIO) and its metabolic complications such as adiposity, dyslipidemia, inflammation, hepatic steatosis, and insulin resistance.
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Affiliation(s)
- Eun-Young Kwon
- Department of Food Science and Nutrition, Kyungpook National University, 1370 San-Kyuk Dong Puk-Ku, Daegu 41566, Korea.
- Center for Food and Nutritional Genomics Research, Kyungpook National University, 1370 San-Kyuk Dong Puk-Ku, Daegu 41566, Korea.
| | - Jeonghyeon Lee
- Department of Food Science and Nutrition, Kyungpook National University, 1370 San-Kyuk Dong Puk-Ku, Daegu 41566, Korea.
| | - Ye Jin Kim
- Department of Food Science and Nutrition, Kyungpook National University, 1370 San-Kyuk Dong Puk-Ku, Daegu 41566, Korea.
| | - Ara Do
- Department of Food Science and Nutrition, Kyungpook National University, 1370 San-Kyuk Dong Puk-Ku, Daegu 41566, Korea.
| | - Ji-Young Choi
- Department of Food Science and Nutrition, Kyungpook National University, 1370 San-Kyuk Dong Puk-Ku, Daegu 41566, Korea.
- Center for Food and Nutritional Genomics Research, Kyungpook National University, 1370 San-Kyuk Dong Puk-Ku, Daegu 41566, Korea.
| | - Su-Jung Cho
- Department of Food Science and Nutrition, Kyungpook National University, 1370 San-Kyuk Dong Puk-Ku, Daegu 41566, Korea.
- Center for Food and Nutritional Genomics Research, Kyungpook National University, 1370 San-Kyuk Dong Puk-Ku, Daegu 41566, Korea.
| | - Un Ju Jung
- Department of Food Science and Nutrition, Pukyong National University, Busan 608-737, Korea.
| | - Mi-Kyung Lee
- Department of Food and Nutrition, Sunchon National University, Suncheon 540-950, Korea.
| | - Yong Bok Park
- School of Life Sciences and Biotechnology, Kyungpook National University, 1370 San-Kyuk Dong Puk-Ku, Daegu 41566, Korea.
| | - Myung-Sook Choi
- Department of Food Science and Nutrition, Kyungpook National University, 1370 San-Kyuk Dong Puk-Ku, Daegu 41566, Korea.
- Center for Food and Nutritional Genomics Research, Kyungpook National University, 1370 San-Kyuk Dong Puk-Ku, Daegu 41566, Korea.
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Lausten-Thomsen U, Christiansen M, Hedley PL, Nielsen TRH, Fonvig CE, Pedersen O, Hansen T, Holm JC. Reference values for fasting serum resistin in healthy children and adolescents. Clin Chim Acta 2017; 469:161-165. [DOI: 10.1016/j.cca.2017.04.002] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2017] [Revised: 04/04/2017] [Accepted: 04/05/2017] [Indexed: 10/19/2022]
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Tortosa-Caparrós E, Navas-Carrillo D, Marín F, Orenes-Piñero E. Anti-inflammatory effects of omega 3 and omega 6 polyunsaturated fatty acids in cardiovascular disease and metabolic syndrome. Crit Rev Food Sci Nutr 2017; 57:3421-3429. [DOI: 10.1080/10408398.2015.1126549] [Citation(s) in RCA: 162] [Impact Index Per Article: 20.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Affiliation(s)
- Esther Tortosa-Caparrós
- Department of Cardiology, Hospital Clínico Universitario Virgen de la Arrixaca, Instituto Murciano de Investigación Biosanitaria Virgen de la Arrixaca (IMIB-Arrixaca), Universidad de Murcia, Murcia, Spain
| | - Diana Navas-Carrillo
- Department of Surgery, Hospital de la Vega Lorenzo Guirao, University of Murcia, Murcia, Spain
| | - Francisco Marín
- Department of Cardiology, Hospital Clínico Universitario Virgen de la Arrixaca, Instituto Murciano de Investigación Biosanitaria Virgen de la Arrixaca (IMIB-Arrixaca), Universidad de Murcia, Murcia, Spain
| | - Esteban Orenes-Piñero
- Department of Cardiology, Hospital Clínico Universitario Virgen de la Arrixaca, Instituto Murciano de Investigación Biosanitaria Virgen de la Arrixaca (IMIB-Arrixaca), Universidad de Murcia, Murcia, Spain
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Antonio de Luis D, Aller R, Izaola O, Primo D, Bachiller R. The rs10401670 variant in resistin gene improved insulin resistance response and metabolic parameters secondaries to weight loss after a hypocaloric diet. Clin Nutr ESPEN 2017; 14:14-18. [PMID: 28531393 DOI: 10.1016/j.clnesp.2016.04.028] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2015] [Revised: 04/20/2016] [Accepted: 04/20/2016] [Indexed: 11/17/2022]
Abstract
BACKGROUND The SNP 3'UTR C/T (rs10401670), it is a polymorphism that has been associated with diabetes mellitus and it has been scarcely studied before. As far as we know, no studies on interaction among diet intervention, rs10401670 variant of RETN and metabolic response has been realized. OBJECTIVE Our aim was to analyze the effects of the rs10401670 RETN gene polymorphism on insulin resistance response and metabolic changes secondary to weight loss after 3 months of a hypocaloric diet in adults obese patients without diabetes mellitus. DESIGN A Caucasian population of 135 obese patients without diabetes mellitus was analyzed. Before and after 3 months on a low fat hypocaloric diet, an anthropometric evaluation, an assessment of nutritional intake and a biochemical analysis were performed. The statistical analysis was performed for the combined CT and TT as a group (minor allele group) and wild type CC as second group (major allele group) (dominant model). RESULTS Forty nine patients (36.3%) had the genotype CC (major allele group) and 86 (63.7%) patients had the next genotypes; CT (67 patients, 49.6%) or TT (19 patients, 14.1%) (minor allele group). After dietary treatment and in major allele group, weight, BMI, fat mass, systolic blood pressure and waist circumference decreases were similar than minor allele group. In T allele carriers, fasting plasma glucose, insulin, HOMA-IR, total cholesterol and LDL cholesterol levels decreased significantly. In non T allele carriers and after dietary treatment, only LDL cholesterol and total cholesterol decreased. In non T Allele carriers, the decrease in total cholesterol was -15.1 ± 18.3 mg/dl (decrease in T Allele carriers -18.3 ± 15.7 mg/dl: p > 0.05), LDL-cholesterol was -14.3 ± 18.5 mg/dl (decrease in T Allele carriers -17.3 ± 10.1 mg/dl:p > 0.05), fasting glucose plasma -2.2 ± 1.5 mg/dL (decrease in T Allele carriers -4.8 ± 1.2 mg/dL: p = 0.02), insulin -1.1 ± 2.0 mUI/L (decrease in T Allele carriers -6.3 ± 1.9 mUI/L: p = 0.001) and HOMA-IR -0.2 ± 1.0 (decrease in T Allele carriers -1.8 ± 1.4: p = 0.005). Leptin levels decrease in both genotypes after dietary treatment (-21.1 ± 8.5 ng/dL in nonT Allele carriers vs -16.2 ± 10.2 ng/dL in T Allele carriers:p > 0.05). Resistin remained unchanged in both groups. CONCLUSION In our study in non-diabetic obese subjects, we describe an association of rs10401670T allele with a better metabolic response (glucose, insulin and HOMA-IR) secondary to weight loss with a hypocaloric diet.
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Affiliation(s)
- Daniel Antonio de Luis
- Center of Investigation of Endocrinology and Nutrition, Medicine School and Dept Endocrinology and Nutrition, Hospital Clinico Universitario, University of Valladolid, Valladolid Spain.
| | - Rocío Aller
- Center of Investigation of Endocrinology and Nutrition, Medicine School and Dept Endocrinology and Nutrition, Hospital Clinico Universitario, University of Valladolid, Valladolid Spain
| | - Olatz Izaola
- Center of Investigation of Endocrinology and Nutrition, Medicine School and Dept Endocrinology and Nutrition, Hospital Clinico Universitario, University of Valladolid, Valladolid Spain
| | - David Primo
- Center of Investigation of Endocrinology and Nutrition, Medicine School and Dept Endocrinology and Nutrition, Hospital Clinico Universitario, University of Valladolid, Valladolid Spain
| | - R Bachiller
- Center of Investigation of Endocrinology and Nutrition, Medicine School and Dept Endocrinology and Nutrition, Hospital Clinico Universitario, University of Valladolid, Valladolid Spain
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de Luis DA, Izaola O, Primo D, de la Fuente B, Mulero I, Aller R. The rs1862513 Variant in Resistin Gene-Modified Insulin Resistance and Insulin Levels after Weight Loss Secondary to Hypocaloric Diet. ANNALS OF NUTRITION AND METABOLISM 2017; 69:256-262. [PMID: 28064279 DOI: 10.1159/000453676] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/27/2016] [Accepted: 11/21/2016] [Indexed: 11/19/2022]
Abstract
BACKGROUND/AIMS Polymorphisms of a single nucleotide in RETN have been associated with indexes of insulin resistance. Our aim was to analyze the effects of the rs1862513 RETN gene polymorphism on insulin resistance, insulin levels, and resistin levels changes after 3 months of a low-fat hypocaloric diet. DESIGN A Caucasian population of 133 obese patients was analyzed before and after 3 months on a low-fat hypocaloric diet. RESULTS Fifty-six patients (42.1%) had the genotype GG (wild group) and 77 (57.9%) patients had the other genotypes; GC (59 patients, 44.4%) or CC (18 patients, 13.5%; mutant group). In wild and mutant genotype groups, weight, body mass index, fat mass, waist circumference, and systolic blood pressure decreased. In the wild genotype group, the decrease in total cholesterol was -13.1 ± 25.3 mg/dL (vs. -4.4 ± 13.7 mg/dL in mutant group: p = 0.004 for group deltas), low density lipoprotein (LDL)-cholesterol was -13.0 ± 21.5 mg/dL (-4.3 ± 10.5 mg/dL: p = 0.007), glucose -7.2 ± 3.5 mg/dL (-0.8 ± 0.2 mg/dL: p = 0.01), insulin -5.6 ± 2.5 mUI/L (-2.9 ± 1.2 mUI/L: p = 0.03) and homeostasis model assessment-insulin resistance (HOMA-IR) -2.5 ± 1.1 (-0.6 ± 1.4: p = 0.02). Leptin levels decreased in both genotypes (-10.1 ± 9.5 ng/dL in wild type group vs. -13.1 ± 0.2 ng/dL in mutant type group: p > 0.05). CONCLUSION The present study suggests that the G/G genotype of RETN rs1862513 could be a predictor of the reduction of HOMA-IR, insulin, fasting glucose and LDL cholesterol secondary to a hypocaloric diet in obese subjects.
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Affiliation(s)
- Daniel Antonio de Luis
- Center of Investigation of Endocrinology and Nutrition, Medicine School and Department of Endocrinology and Nutrition Hospital Clinico Universitario, University of Valladolid, Valladolid, Spain
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Luo JW, Zheng X, Cheng GC, Ye QH, Deng YZ, Wu L. Resistin-induced cardiomyocyte hypertrophy is inhibited by apelin through the inactivation of extracellular signal-regulated kinase signaling pathway in H9c2 embryonic rat cardiomyocytes. Biomed Rep 2016; 5:473-478. [PMID: 27699016 DOI: 10.3892/br.2016.749] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2016] [Accepted: 08/18/2016] [Indexed: 11/06/2022] Open
Abstract
It has been reported that resistin induces, whereas apelin inhibits cardiac hypertrophy. However, the underlying molecular mechanisms of apelin inhibiting resistin-induced cardiac hypertrophy remain unclear. The aim of the current study is to investigate the effects of apelin on resistin-induced cardiomyocyte hypertrophy and elucidate the underlying molecular mechanism. H9c2 cells were used in the present study, and cell surface area and protein synthesis were evaluated. Reverse transcription-quantitative polymerase chain reaction was performed to analyze the expression levels of hypertrophic markers, brain natriuretic peptide (BNP) and β-myosin heavy chain (β-MHC). In addition, western blotting was conducted to examine phosphorylation of extracellular signal-regulated kinase (ERK)1/2. Following treatment of H9c2 cells with resistin, cell surface area, protein synthesis, and BNP and β-MHC mRNA expression levels were increased. Subsequent to co-treatment of H9c2 cells with apelin and resistin, lead to the inhibition of resistin-induced hypertrophic effects by apelin. In addition, treatment with resistin increased phosphorylation of ERK1/2, whereas pretreatment with apelin decreased phosphorylation of ERK1/2, which was increased by resistin. These results indicate that resistin-induced cardiac hypertrophy is inhibited by apelin via inactivation of ERK1/2 cell signaling.
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Affiliation(s)
- Jian-Wei Luo
- Department of Cardiovascular Surgery, The Affiliated Cardiovascular Hospital of Shanxi Medical University, Shanxi Cardiovascular Hospital (Institute), Taiyuan, Shanxi 030024, P.R. China
| | - Xian Zheng
- Department of Cardiovascular Surgery, The Affiliated Cardiovascular Hospital of Shanxi Medical University, Shanxi Cardiovascular Hospital (Institute), Taiyuan, Shanxi 030024, P.R. China
| | - Guan-Chang Cheng
- Department of Cardiology, Huaihe Hospital of Henan University, Kaifeng, Henan 475000, P.R. China
| | - Qun-Hui Ye
- Department of Cardiology, Huaihe Hospital of Henan University, Kaifeng, Henan 475000, P.R. China
| | - Yong-Zhi Deng
- Department of Cardiovascular Surgery, The Affiliated Cardiovascular Hospital of Shanxi Medical University, Shanxi Cardiovascular Hospital (Institute), Taiyuan, Shanxi 030024, P.R. China
| | - Lin Wu
- Department of Cardiology, Huaihe Hospital of Henan University, Kaifeng, Henan 475000, P.R. China
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Tucureanu MM, Butoi E, Gan AM, Stan D, Constantinescu CA, Calin M, Simionescu M, Manduteanu I. Amendment of the cytokine profile in macrophages subsequent to their interaction with smooth muscle cells: Differential modulation by fractalkine and resistin. Cytokine 2016; 83:250-261. [DOI: 10.1016/j.cyto.2016.04.019] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2015] [Revised: 04/28/2016] [Accepted: 04/28/2016] [Indexed: 11/26/2022]
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