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Martinez P, Grant WB. Vitamin D: What role in obesity-related cancer? Semin Cancer Biol 2025; 112:135-149. [PMID: 40194750 DOI: 10.1016/j.semcancer.2025.03.007] [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: 12/06/2024] [Revised: 03/16/2025] [Accepted: 03/29/2025] [Indexed: 04/09/2025]
Abstract
Obesity is an important risk factor for incidence and death for many types of cancer. Vitamin D reduces risk of incidence and death for many types of cancer. This review outlines the mechanisms by which obesity increases risk of cancer, how vitamin D reduces risk of cancer, and the extent to which vitamin D counters the effects of obesity in cancer. Vitamin D is a partial ally against some of obesity's pro-carcinogenic effects, notably by reducing inflammation and regulating sex hormone receptors, leptin resistance, cellular energy metabolism, the microbiome, and hypoxia. However, it can act stronger in against the renin-angiotensin system, insulin resistance, and oxidative stress in cancer. Additionally, excess fat tissue sequesters vitamin D and, along with its dilution in increased body volume, further reduces its bioavailability and serum concentration, limiting its protective effects against cancer. In conclusion, while vitamin D cannot reverse obesity, it plays a significant role in mitigating its pro-carcinogenic effects by targeting several mechanisms.
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Affiliation(s)
| | - William B Grant
- Sunlight, Nutrition, and Health Research Center, 1745 Pacific Ave., Ste. 504, San Francisco, CA 94109, USA.
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Morita S, Mochizuki Y, Kondo T, Matsuda Y, Ohmori T, Yoshimura A, Fukushima R. Amlodipine improves symmetric dimethylarginine in dogs with chronic kidney disease. Front Vet Sci 2025; 12:1570349. [PMID: 40370820 PMCID: PMC12075874 DOI: 10.3389/fvets.2025.1570349] [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: 02/03/2025] [Accepted: 04/11/2025] [Indexed: 05/16/2025] Open
Abstract
Introduction In canines, chronic kidney disease (CKD) is frequently associated with high blood pressure. Amlodipine is used to treat hypertension in dogs, and we anticipated that amlodipine administration might improve renal function in dogs. However, the effect of amlodipine on canine renal function is unknown. Therefore, this study evaluated changes in symmetric dimethylarginine (SDMA) levels before and after amlodipine administration in pet dogs that had been diagnosed with CKD based on persistently elevated SDMA levels and were being treated with amlodipine alone for any reason. We also conducted a comparative investigation of whether there were any differences in SDMA changes depending on whether these dogs with CKD had hypertension. Methods This study employed a retrospective design. The study subjects were pet dogs that exhibited persistently elevated SDMA (≥14 μg/dL), were diagnosed with CKD, and were treated with amlodipine. Profile data such as breed, sex, and age, as well as data on blood chemistry tests, blood pressure, heart rate, and echocardiograms before and after amlodipine administration, were collected. Forty-five dogs were included in the study, of which 20 were hypertensive (HT: systolic arterial pressure ≥160 mmHg) and 25 were non-hypertensive (Non-HT: systolic arterial pressure <160 mmHg). Results Mean SDMA was significantly lower after drug administration compared with before administration in both the HT and Non-HT groups. Moreover, we found that cardiac output (CO) increased in all dogs with CKD treated with amlodipine. Blood pressure measurements showed that the blood pressure decreased in both the HT and Non-HT groups. Discussion It is believed that the increase in CO due to amlodipine administration increases glomerular filtration rate, which may have led to a decrease in SDMA levels. Based on the rate of decrease in systolic arterial pressure, we considered that amlodipine might decrease blood pressure by a greater amount in patients with higher levels of hypertension. In this study, we showed that amlodipine administration improved SDMA in dogs with CKD regardless of whether they were hypertension. We also showed that amlodipine could be safely used to treat normotensive dogs.
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Affiliation(s)
- Shohei Morita
- Koganei Animal Medical Emergency Center, Tokyo University of Agriculture and Technology, Tokyo, Japan
| | - Youhei Mochizuki
- Faculty of Veterinary Medicine, Okayama University of Science, Okayama, Japan
| | - Takahiro Kondo
- Koganei Animal Medical Emergency Center, Tokyo University of Agriculture and Technology, Tokyo, Japan
| | - Yasuyoshi Matsuda
- Koganei Animal Medical Emergency Center, Tokyo University of Agriculture and Technology, Tokyo, Japan
| | - Takahiro Ohmori
- Koganei Animal Medical Emergency Center, Tokyo University of Agriculture and Technology, Tokyo, Japan
| | - Aritada Yoshimura
- Animal Medical Center, Tokyo University of Agriculture and Technology, Tokyo, Japan
| | - Ryuji Fukushima
- Koganei Animal Medical Emergency Center, Tokyo University of Agriculture and Technology, Tokyo, Japan
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Byeon H. Impact of night sentry duties on cardiometabolic health in military personnel. World J Cardiol 2025; 17:102133. [PMID: 40308619 PMCID: PMC12038707 DOI: 10.4330/wjc.v17.i4.102133] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2024] [Revised: 02/14/2025] [Accepted: 02/27/2025] [Indexed: 04/21/2025] Open
Abstract
This article examines the study by Lin et al, which explores the effects of night sentry duties on cardiometabolic health in military personnel. The research identifies significant correlations between the frequency of night shifts and negative cardiometabolic outcomes, such as elevated resting pulse rates and lowered levels of high-density lipoprotein cholesterol. These outcomes underscore the health risks linked to partial sleep deprivation, a common challenge in military environments. The editorial highlights the clinical significance of these findings, advocating for the implementation of targeted health interventions to mitigate these risks. Strategies such as structured sleep recovery programs and lifestyle modifications are recommended to improve the health management of military personnel engaged in nocturnal duties. By addressing these issues, military health management can better safeguard the well-being and operational readiness of its personnel.
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Affiliation(s)
- Haewon Byeon
- Department of Future Technology, Worker's Care and Digital Health Lab, Korea University of Technology and Education, Cheonan 31253, South Korea.
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Xi Y, Bao Z, Guo Q, Wang J, Jing Z, Di J, Yang K. Reproductive Toxicity Induced by Serotonin-Norepinephrine Reuptake Inhibitors: A Pharmacovigilance Analysis From 2004 to 2023 Based on the FAERS Database. CNS Neurosci Ther 2024; 30:e70176. [PMID: 39670536 PMCID: PMC11638886 DOI: 10.1111/cns.70176] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2024] [Revised: 11/28/2024] [Accepted: 11/30/2024] [Indexed: 12/14/2024] Open
Abstract
AIM Serotonin-norepinephrine reuptake inhibitors (SNRIs) have been extensively utilized for the treatment of depression and anxiety disorders. Clinical trials and real-world data suggest that SNRIs may cause reproductive toxicity. To comprehensively assess this association, we conducted a pharmacovigilance study. METHODS We utilized various disproportionality analysis algorithms, including reporting odds ratio (ROR), proportional reporting ratio (PRR), bayesian confidence propagation neural network (BCPNN), and multi-item gamma poisson shrinker (MGPS), to assess the significance of reproductive toxicity-related adverse events (AEs) reported to FDA Adverse Event Reporting System (FAERS) from January 2004 to December 2023, with subgroup analysis conducted by sex and age. RESULTS Duloxetine and venlafaxine were associated with 14 and 25 AE signals related to reproductive toxicity, respectively, with erectile dysfunction (ED) and retrograde ejaculation identified as shared important medical events (IMEs). ED had the highest reporting frequency, strongest in venlafaxine-treated patients under 45 years (ROR 4.34, PRR 4.33, IC 2.09, EBGM 4.25). Retrograde ejaculation was newly identified. With decreasing incidence, venlafaxine's median ED onset was 122.5 days and duloxetine's 38 days. CONCLUSION Our study provides evidence through an extensive analysis of the large-scale real-world FAERS database, aiding healthcare professionals in mitigating, and prioritizing SNRI-related reproductive toxicity AEs.
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Affiliation(s)
- Yujia Xi
- Department of UrologySecond Hospital of Shanxi Medical UniversityTaiyuanChina
- Male Reproductive Medicine CenterShanxi Medical UniversityJinzhongChina
| | - Zhuocheng Bao
- Male Reproductive Medicine CenterShanxi Medical UniversityJinzhongChina
| | - Qiang Guo
- Department of UrologySecond Hospital of Shanxi Medical UniversityTaiyuanChina
- Male Reproductive Medicine CenterShanxi Medical UniversityJinzhongChina
| | - Jingqi Wang
- Department of UrologySecond Hospital of Shanxi Medical UniversityTaiyuanChina
- Male Reproductive Medicine CenterShanxi Medical UniversityJinzhongChina
| | - Zhinan Jing
- Male Reproductive Medicine CenterShanxi Medical UniversityJinzhongChina
| | - Jingkai Di
- Department of OrthopedicsSecond Hospital of Shanxi Medical UniversityTaiyuanChina
| | - Ke Yang
- Department of UrologySecond Hospital of Shanxi Medical UniversityTaiyuanChina
- Male Reproductive Medicine CenterShanxi Medical UniversityJinzhongChina
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Li A, Wang Y, Li R, Lin Y, Li Y, Wang Y, Liu W, Yan X. Neuron-derived neurotrophic factor promotes the differentiation of intramuscular and subcutaneous adipocytes in goat. Anim Biotechnol 2024; 35:2346223. [PMID: 38739480 DOI: 10.1080/10495398.2024.2346223] [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] [Indexed: 05/16/2024]
Abstract
Adipocyte play an important role in human health and meat quality by influencing the tenderness, flavor, and juiciness of mutton It has been shown that neuron-derived neurotrophic factor (NENF) is closely related to energy metabolism and adipocyte differentiation in bovine. However, the role of NENF in the goats remains unclear. The aim of this study was to detect the expression of NENF in goat subcutaneous and intramuscular adipocytes, temporal expression profiles of the NENF, and overexpressed NENF on the differentiation of different adipocytes. In this study, PCR amplification successfully cloned the goat NENF gene with a fragment length of 521 bp. In addition, the time point of highest expression of NENF differed between these two adipocytes differentiation processes. Overexpression of NENF in intramuscular and subcutaneous adipocytes promoted the expression levels of differentiation markers CEBPβ and SREBP, which in turn promoted the differentiation of intramuscular and subcutaneous adipocytes. This study will provide basic data for further study of the role of goats in goat adipocyte differentiation and for the final elucidation of its molecular mechanisms in regulating goat adipocyte deposition.
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Affiliation(s)
- An Li
- College of Animal and Veterinary Sciences, Southwest Minzu University, Chengdu, China
- Key Laboratory of Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Utilization, Ministry of Education, Southwest Minzu University, Chengdu, China
- Key Laboratory of Sichuan Province for Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Exploitation, Southwest Minzu University, Chengdu, China
| | - Youli Wang
- College of Animal and Veterinary Sciences, Southwest Minzu University, Chengdu, China
- Key Laboratory of Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Utilization, Ministry of Education, Southwest Minzu University, Chengdu, China
- Key Laboratory of Sichuan Province for Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Exploitation, Southwest Minzu University, Chengdu, China
| | - Ruiwen Li
- Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Yaqiu Lin
- College of Animal and Veterinary Sciences, Southwest Minzu University, Chengdu, China
- Key Laboratory of Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Utilization, Ministry of Education, Southwest Minzu University, Chengdu, China
| | - Yanyan Li
- College of Animal and Veterinary Sciences, Southwest Minzu University, Chengdu, China
- Key Laboratory of Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Utilization, Ministry of Education, Southwest Minzu University, Chengdu, China
- Key Laboratory of Sichuan Province for Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Exploitation, Southwest Minzu University, Chengdu, China
| | - Yong Wang
- College of Animal and Veterinary Sciences, Southwest Minzu University, Chengdu, China
- Key Laboratory of Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Utilization, Ministry of Education, Southwest Minzu University, Chengdu, China
- Key Laboratory of Sichuan Province for Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Exploitation, Southwest Minzu University, Chengdu, China
| | - Wei Liu
- College of Animal and Veterinary Sciences, Southwest Minzu University, Chengdu, China
- Key Laboratory of Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Utilization, Ministry of Education, Southwest Minzu University, Chengdu, China
- Key Laboratory of Sichuan Province for Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Exploitation, Southwest Minzu University, Chengdu, China
| | - Xiong Yan
- College of Animal and Veterinary Sciences, Southwest Minzu University, Chengdu, China
- Key Laboratory of Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Utilization, Ministry of Education, Southwest Minzu University, Chengdu, China
- Key Laboratory of Sichuan Province for Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Exploitation, Southwest Minzu University, Chengdu, China
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Rajan PK, Udoh UAS, Finley R, Pierre SV, Sanabria J. The Biological Clock of Liver Metabolism in Metabolic Dysfunction-Associated Steatohepatitis Progression to Hepatocellular Carcinoma. Biomedicines 2024; 12:1961. [PMID: 39335475 PMCID: PMC11428469 DOI: 10.3390/biomedicines12091961] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2024] [Revised: 08/12/2024] [Accepted: 08/19/2024] [Indexed: 09/30/2024] Open
Abstract
Circadian rhythms are endogenous behavioral or physiological cycles that are driven by a daily biological clock that persists in the absence of geophysical or environmental temporal cues. Circadian rhythm-related genes code for clock proteins that rise and fall in rhythmic patterns driving biochemical signals of biological processes from metabolism to physiology and behavior. Clock proteins have a pivotal role in liver metabolism and homeostasis, and their disturbances are implicated in various liver disease processes. Encoded genes play critical roles in the initiation and progression of metabolic dysfunction-associated steatohepatitis (MASH) to hepatocellular carcinoma (HCC) and their proteins may become diagnostic markers as well as therapeutic targets. Understanding molecular and metabolic mechanisms underlying circadian rhythms will aid in therapeutic interventions and may have broader clinical applications. The present review provides an overview of the role of the liver's circadian rhythm in metabolic processes in health and disease, emphasizing MASH progression and the oncogenic associations that lead to HCC.
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Affiliation(s)
- Pradeep Kumar Rajan
- Marshall Institute for Interdisciplinary Research, Huntington, WV 25703, USA
- Department of Surgery, School of Medicine, Marshall University, Huntington, WV 25701, USA
| | - Utibe-Abasi S Udoh
- Marshall Institute for Interdisciplinary Research, Huntington, WV 25703, USA
- Department of Surgery, School of Medicine, Marshall University, Huntington, WV 25701, USA
| | - Robert Finley
- Department of Surgery, School of Medicine, Marshall University, Huntington, WV 25701, USA
| | - Sandrine V Pierre
- Marshall Institute for Interdisciplinary Research, Huntington, WV 25703, USA
| | - Juan Sanabria
- Marshall Institute for Interdisciplinary Research, Huntington, WV 25703, USA
- Department of Surgery, School of Medicine, Marshall University, Huntington, WV 25701, USA
- Department of Nutrition and Metabolomic Core Facility, School of Medicine, Case Western Reserve University, Cleveland, OH 44100, USA
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Chen N, Guo L, Wang L, Dai S, Zhu X, Wang E. Sleep fragmentation exacerbates myocardial ischemia‒reperfusion injury by promoting copper overload in cardiomyocytes. Nat Commun 2024; 15:3834. [PMID: 38714741 PMCID: PMC11076509 DOI: 10.1038/s41467-024-48227-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2023] [Accepted: 04/23/2024] [Indexed: 05/10/2024] Open
Abstract
Sleep disorders increase the risk and mortality of heart disease, but the brain-heart interaction has not yet been fully elucidated. Cuproptosis is a copper-dependent type of cell death activated by the excessive accumulation of intracellular copper. Here, we showed that 16 weeks of sleep fragmentation (SF) resulted in elevated copper levels in the male mouse heart and exacerbated myocardial ischemia-reperfusion injury with increased myocardial cuproptosis and apoptosis. Mechanistically, we found that SF promotes sympathetic overactivity, increases the germination of myocardial sympathetic nerve terminals, and increases the level of norepinephrine in cardiac tissue, thereby inhibits VPS35 expression and leads to impaired ATP7A related copper transport and copper overload in cardiomyocytes. Copper overload further leads to exacerbated cuproptosis and apoptosis, and these effects can be rescued by excision of the sympathetic nerve or administration of copper chelating agent. Our study elucidates one of the molecular mechanisms by which sleep disorders aggravate myocardial injury and suggests possible targets for intervention.
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Affiliation(s)
- Na Chen
- Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha, China
| | - Lizhe Guo
- Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha, China
| | - Lu Wang
- Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha, China
| | - Sisi Dai
- Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha, China
| | - Xiaocheng Zhu
- Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha, China
| | - E Wang
- Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha, China.
- National Clinical Research Center for Geriatric Disorders (Xiangya Hospital), Changsha, China.
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Osakabe N, Shimizu T, Fujii Y, Fushimi T, Calabrese V. Sensory Nutrition and Bitterness and Astringency of Polyphenols. Biomolecules 2024; 14:234. [PMID: 38397471 PMCID: PMC10887135 DOI: 10.3390/biom14020234] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2024] [Revised: 02/05/2024] [Accepted: 02/05/2024] [Indexed: 02/25/2024] Open
Abstract
Recent studies have demonstrated that the interaction of dietary constituents with taste and olfactory receptors and nociceptors expressed in the oral cavity, nasal cavity and gastrointestinal tract regulate homeostasis through activation of the neuroendocrine system. Polyphenols, of which 8000 have been identified to date, represent the greatest diversity of secondary metabolites in plants, most of which are bitter and some of them astringent. Epidemiological studies have shown that polyphenol intake contributes to maintaining and improving cardiovascular, cognitive and sensory health. However, because polyphenols have very low bioavailability, the mechanisms of their beneficial effects are unknown. In this review, we focused on the taste of polyphenols from the perspective of sensory nutrition, summarized the results of previous studies on their relationship with bioregulation and discussed their future potential.
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Affiliation(s)
- Naomi Osakabe
- Functional Control Systems, Graduate School of Engineering and Science, Shibaura Institute of Technology, Tokyo 135-8548, Japan
- Systems Engineering and Science, Graduate School of Engineering and Science, Shibaura Institute of Technology, Tokyo 135-8548, Japan;
- Department of Bio-Science and Engineering, Faculty of System Science and Engineering, Shibaura Institute of Technology, Tokyo 135-8548, Japan; (T.S.); (Y.F.)
| | - Takafumi Shimizu
- Department of Bio-Science and Engineering, Faculty of System Science and Engineering, Shibaura Institute of Technology, Tokyo 135-8548, Japan; (T.S.); (Y.F.)
| | - Yasuyuki Fujii
- Department of Bio-Science and Engineering, Faculty of System Science and Engineering, Shibaura Institute of Technology, Tokyo 135-8548, Japan; (T.S.); (Y.F.)
| | - Taiki Fushimi
- Systems Engineering and Science, Graduate School of Engineering and Science, Shibaura Institute of Technology, Tokyo 135-8548, Japan;
| | - Vittorio Calabrese
- Department of Biomedical and Biotechnological Sciences, University of Catania, 95125 Catania, Italy;
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Abbas A, Hammad AS, Al-Shafai M. The role of genetic and epigenetic GNAS alterations in the development of early-onset obesity. MUTATION RESEARCH. REVIEWS IN MUTATION RESEARCH 2024; 793:108487. [PMID: 38103632 DOI: 10.1016/j.mrrev.2023.108487] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/09/2023] [Revised: 12/06/2023] [Accepted: 12/11/2023] [Indexed: 12/19/2023]
Abstract
BACKGROUND GNAS (guanine nucleotide-binding protein, alpha stimulating) is an imprinted gene that encodes Gsα, the α subunit of the heterotrimeric stimulatory G protein. This subunit mediates the signalling of a diverse array of G protein-coupled receptors (GPCRs), including the melanocortin 4 receptor (MC4R) that serves a pivotal role in regulating food intake, energy homoeostasis, and body weight. Genetic or epigenetic alterations in GNAS are known to cause pseudohypoparathyroidism in its different subtypes and have been recently associated with isolated, early-onset, severe obesity. Given the diverse biological functions that Gsα serves, multiple molecular mechanisms involving various GPCRs, such as MC4R, β2- and β3-adrenoceptors, and corticotropin-releasing hormone receptor, have been implicated in the pathophysiology of severe, early-onset obesity that results from genetic or epigenetic GNAS changes. SCOPE OF REVIEW This review examines the structure and function of GNAS and provides an overview of the disorders that are caused by defects in this gene and may feature early-onset obesity. Moreover, it elucidates the potential molecular mechanisms underlying Gsα deficiency-induced early-onset obesity, highlighting some of their implications for the diagnosis, management, and treatment of this complex condition. MAJOR CONCLUSIONS Gsα deficiency is an underappreciated cause of early-onset, severe obesity. Therefore, screening children with unexplained, severe obesity for GNAS defects is recommended, to enhance the molecular diagnosis and management of this condition.
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Affiliation(s)
- Alaa Abbas
- Department of Biomedical Sciences, College of Health Sciences, QU Health, Qatar University, P.O. Box 2713, Doha, Qatar
| | - Ayat S Hammad
- Department of Biomedical Sciences, College of Health Sciences, QU Health, Qatar University, P.O. Box 2713, Doha, Qatar; Biomedical Research Center, Qatar University, P.O. Box 2713, Doha, Qatar
| | - Mashael Al-Shafai
- Department of Biomedical Sciences, College of Health Sciences, QU Health, Qatar University, P.O. Box 2713, Doha, Qatar; Biomedical Research Center, Qatar University, P.O. Box 2713, Doha, Qatar.
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Muta O, Oyama S, Odaka M, Shimizu K, Katsuragawa S, Suzuki K, Fushimi T, Fujii Y, Akagi R, Osakabe N. Cinnamtannin A2, (-)-epicatechin tetramer, attenuates skeletal muscle wasting in disuse atrophy model mice induced by hindlimb suspension. J Clin Biochem Nutr 2023; 73:124-130. [PMID: 37700845 PMCID: PMC10493217 DOI: 10.3164/jcbn.23-12] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2023] [Accepted: 04/08/2023] [Indexed: 09/14/2023] Open
Abstract
The impact of repeated administration of cinntamtannin A2 (A2, 25 μg/kg) on skeletal muscle disuse atrophy model mice induced by hindlimb suspension for 14 days was examined. In soleus, weight loss and a reduction in the average myofibre size with shifting to the smaller side of the peak were observed in the suspension-vehicle group, but A2 reduced these changes. Average myofibre size significantly increased in ground-A2 compared to ground-vehicle. A marked increase in the dephosphorylation of forkhead box O (FoxO) 3a by the suspension was reduced by A2. The phosphorylation of protein kinase B (Akt) and eukaryotic translation initiation factor 4E-binding protein (4EBP)-1 were significantly increased by the treatment of A2. In addition, a single dose of A2 increased dramatically in the 24-h excretion of catecholamines in urine. These results suggest that A2 administration results in sympathetic nerve activation and promotes hypertrophy while inhibiting the progress of disuse muscle atrophy.
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Affiliation(s)
- Orie Muta
- Functional Control Systems, Graduate School of Engineering and Science, Shibaura Institute of Technology, 307 Fukasaku, Minumaku, Saitama 337-8570, Japan
| | - Shiori Oyama
- Functional Control Systems, Graduate School of Engineering and Science, Shibaura Institute of Technology, 307 Fukasaku, Minumaku, Saitama 337-8570, Japan
| | - Minayu Odaka
- Department of Bio-science and Engineering, Faculty of System Science and Engineering, Shibaura Institute of Technology, 307 Fukasaku, Minumaku, Saitama 337-8570, Japan
| | - Kenta Shimizu
- Department of Bio-science and Engineering, Faculty of System Science and Engineering, Shibaura Institute of Technology, 307 Fukasaku, Minumaku, Saitama 337-8570, Japan
| | - Sae Katsuragawa
- Department of Bio-science and Engineering, Faculty of System Science and Engineering, Shibaura Institute of Technology, 307 Fukasaku, Minumaku, Saitama 337-8570, Japan
| | - Kenta Suzuki
- Department of Bio-science and Engineering, Faculty of System Science and Engineering, Shibaura Institute of Technology, 307 Fukasaku, Minumaku, Saitama 337-8570, Japan
| | - Taiki Fushimi
- Functional Control Systems, Graduate School of Engineering and Science, Shibaura Institute of Technology, 307 Fukasaku, Minumaku, Saitama 337-8570, Japan
| | - Yasuyuki Fujii
- Functional Control Systems, Graduate School of Engineering and Science, Shibaura Institute of Technology, 307 Fukasaku, Minumaku, Saitama 337-8570, Japan
| | - Ryota Akagi
- Functional Control Systems, Graduate School of Engineering and Science, Shibaura Institute of Technology, 307 Fukasaku, Minumaku, Saitama 337-8570, Japan
- Department of Bio-science and Engineering, Faculty of System Science and Engineering, Shibaura Institute of Technology, 307 Fukasaku, Minumaku, Saitama 337-8570, Japan
| | - Naomi Osakabe
- Functional Control Systems, Graduate School of Engineering and Science, Shibaura Institute of Technology, 307 Fukasaku, Minumaku, Saitama 337-8570, Japan
- Department of Bio-science and Engineering, Faculty of System Science and Engineering, Shibaura Institute of Technology, 307 Fukasaku, Minumaku, Saitama 337-8570, Japan
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Cincotta AH. Brain Dopamine-Clock Interactions Regulate Cardiometabolic Physiology: Mechanisms of the Observed Cardioprotective Effects of Circadian-Timed Bromocriptine-QR Therapy in Type 2 Diabetes Subjects. Int J Mol Sci 2023; 24:13255. [PMID: 37686060 PMCID: PMC10487918 DOI: 10.3390/ijms241713255] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2023] [Revised: 07/19/2023] [Accepted: 07/27/2023] [Indexed: 09/10/2023] Open
Abstract
Despite enormous global efforts within clinical research and medical practice to reduce cardiovascular disease(s) (CVD), it still remains the leading cause of death worldwide. While genetic factors clearly contribute to CVD etiology, the preponderance of epidemiological data indicate that a major common denominator among diverse ethnic populations from around the world contributing to CVD is the composite of Western lifestyle cofactors, particularly Western diets (high saturated fat/simple sugar [particularly high fructose and sucrose and to a lesser extent glucose] diets), psychosocial stress, depression, and altered sleep/wake architecture. Such Western lifestyle cofactors are potent drivers for the increased risk of metabolic syndrome and its attendant downstream CVD. The central nervous system (CNS) evolved to respond to and anticipate changes in the external (and internal) environment to adapt survival mechanisms to perceived stresses (challenges to normal biological function), including the aforementioned Western lifestyle cofactors. Within the CNS of vertebrates in the wild, the biological clock circuitry surveils the environment and has evolved mechanisms for the induction of the obese, insulin-resistant state as a survival mechanism against an anticipated ensuing season of low/no food availability. The peripheral tissues utilize fat as an energy source under muscle insulin resistance, while increased hepatic insulin resistance more readily supplies glucose to the brain. This neural clock function also orchestrates the reversal of the obese, insulin-resistant condition when the low food availability season ends. The circadian neural network that produces these seasonal shifts in metabolism is also responsive to Western lifestyle stressors that drive the CNS clock into survival mode. A major component of this natural or Western lifestyle stressor-induced CNS clock neurophysiological shift potentiating the obese, insulin-resistant state is a diminution of the circadian peak of dopaminergic input activity to the pacemaker clock center, suprachiasmatic nucleus. Pharmacologically preventing this loss of circadian peak dopaminergic activity both prevents and reverses existing metabolic syndrome in a wide variety of animal models of the disorder, including high fat-fed animals. Clinically, across a variety of different study designs, circadian-timed bromocriptine-QR (quick release) (a unique formulation of micronized bromocriptine-a dopamine D2 receptor agonist) therapy of type 2 diabetes subjects improved hyperglycemia, hyperlipidemia, hypertension, immune sterile inflammation, and/or adverse cardiovascular event rate. The present review details the seminal circadian science investigations delineating important roles for CNS circadian peak dopaminergic activity in the regulation of peripheral fuel metabolism and cardiovascular biology and also summarizes the clinical study findings of bromocriptine-QR therapy on cardiometabolic outcomes in type 2 diabetes subjects.
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Thakkar P, Pauza AG, Murphy D, Paton JFR. Carotid body: an emerging target for cardiometabolic co-morbidities. Exp Physiol 2023; 108:661-671. [PMID: 36999224 PMCID: PMC10988524 DOI: 10.1113/ep090090] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2021] [Accepted: 03/03/2023] [Indexed: 04/01/2023]
Abstract
NEW FINDINGS What is the topic of this review? Regarding the global metabolic syndrome crisis, this review focuses on common mechanisms for high blood sugar and high blood pressure. Connections are made between the homeostatic regulation of blood pressure and blood sugar and their dysregulation to reveal signalling mechanisms converging on the carotid body. What advances does it highlight? The carotid body plays a major part in the generation of excessive sympathetic activity in diabetes and also underpins diabetic hypertension. As treatment of diabetic hypertension is notoriously difficult, we propose that novel receptors within the carotid body may provide a novel treatment strategy. ABSTRACT The maintenance of glucose homeostasis is obligatory for health and survival. It relies on peripheral glucose sensing and signalling between the brain and peripheral organs via hormonal and neural responses that restore euglycaemia. Failure of these mechanisms causes hyperglycaemia or diabetes. Current anti-diabetic medications control blood glucose but many patients remain with hyperglycemic condition. Diabetes is often associated with hypertension; the latter is more difficult to control in hyperglycaemic conditions. We ask whether a better understanding of the regulatory mechanisms of glucose control could improve treatment of both diabetes and hypertension when they co-exist. With the involvement of the carotid body (CB) in glucose sensing, metabolic regulation and control of sympathetic nerve activity, we consider the CB as a potential treatment target for both diabetes and hypertension. We provide an update on the role of the CB in glucose sensing and glucose homeostasis. Physiologically, hypoglycaemia stimulates the release of hormones such as glucagon and adrenaline, which mobilize or synthesize glucose; however, these counter-regulatory responses were markedly attenuated after denervation of the CBs in animals. Also, CB denervation prevents and reverses insulin resistance and glucose intolerance. We discuss the CB as a metabolic regulator (not just a sensor of blood gases) and consider recent evidence of novel 'metabolic' receptors within the CB and putative signalling peptides that may control glucose homeostasis via modulation of the sympathetic nervous system. The evidence presented may inform future clinical strategies in the treatment of patients with both diabetes and hypertension, which may include the CB.
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Affiliation(s)
- Pratik Thakkar
- Manaaki Manawa – the Centre for Heart Research, Department of Physiology, Faculty of Medical and Health SciencesUniversity of AucklandAucklandNew Zealand
| | - Audrys G. Pauza
- Manaaki Manawa – the Centre for Heart Research, Department of Physiology, Faculty of Medical and Health SciencesUniversity of AucklandAucklandNew Zealand
| | - David Murphy
- Molecular Neuroendocrinology Research Group, Bristol Medical School: Translational Health SciencesUniversity of BristolBristolUK
| | - Julian F. R. Paton
- Manaaki Manawa – the Centre for Heart Research, Department of Physiology, Faculty of Medical and Health SciencesUniversity of AucklandAucklandNew Zealand
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Zhao J, Zhang Y, Yin Z, Zhu Y, Xin F, Zhang H, Po SS, Wang H. Impact of proinflammatory epicardial adipose tissue and differentially enhanced autonomic remodeling on human atrial fibrillation. J Thorac Cardiovasc Surg 2023; 165:e158-e174. [PMID: 35461705 DOI: 10.1016/j.jtcvs.2022.03.013] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2022] [Revised: 02/24/2022] [Accepted: 03/04/2022] [Indexed: 11/25/2022]
Abstract
OBJECTIVES The mechanisms underlying atrial fibrillation are yet to be elucidated. We sought to investigate the interactions among autonomic remodeling, epicardial adipose tissue, inflammation, and atrial fibrillation. METHODS Myocardium and adjacent epicardial adipose tissue of the left atrial appendage, right atrial appendage, and pulmonary vein muscle sleeves were obtained from 61 consecutive patients (35 with atrial fibrillation, 26 with no atrial fibrillation) during mitral valve surgeries. Patients were divided into the atrial fibrillation group and no atrial fibrillation group according to the history and Holter monitoring before surgery. Sympathetic and parasympathetic innervation were evaluated by tyrosine hydroxylase and choline acetyltransferase staining, respectively. Atrial fibrosis as well as cytokines/adipokines and related inflammatory proteins and signaling pathways in the epicardial adipose tissue were examined. RESULTS Immunohistochemical studies revealed significantly increased tyrosine hydroxylase (+) and choline acetyltransferase (+) neural elements in the left atrial appendage and pulmonary vein muscle sleeve myocardium, as well as adjacent epicardial adipose tissue in the atrial fibrillation group, particularly the pulmonary vein muscle sleeve sites. The receiver operating curve identified a threshold ratio (tyrosine hydroxylase/choline acetyltransferase) of 0.8986 in the epicardial adipose tissue (sensitivity = 82.86%; specificity = 80.77%; area under the curve = 0.85, 95% confidence interval = 0.76-0.95, P < .0001). More patients with a higher tyrosine hydroxylase/choline acetyltransferase ratio (≥0.8986) had atrial fibrillation. Expression levels of the genes and related proteins of the β1 adrenergic, mitogen-activated protein kinase, and nuclear factor kappa B signaling pathways were higher in patients with a higher tyrosine hydroxylase/choline acetyltransferase ratio. The tyrosine hydroxylase/choline acetyltransferase ratio also correlated with fibrosis. CONCLUSIONS Differentially enhanced autonomic remodeling and proinflammatory and profibrotic cytokines/adipokines in the epicardial adipose tissue adjacent to the pulmonary vein muscle sleeve site may work synergistically to promote atrial fibrillation.
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Affiliation(s)
- Jikai Zhao
- Department of Cardiovascular Surgery, General Hospital of Northern Theater Command, Shenyang, PR China
| | - Yuji Zhang
- Department of Cardiovascular Surgery, General Hospital of Northern Theater Command, Shenyang, PR China
| | - Zongtao Yin
- Department of Cardiovascular Surgery, General Hospital of Northern Theater Command, Shenyang, PR China
| | - Yan Zhu
- Department of Cardiovascular Surgery, General Hospital of Northern Theater Command, Shenyang, PR China
| | - Fangran Xin
- Department of Cardiovascular Surgery, General Hospital of Northern Theater Command, Shenyang, PR China
| | - Huidan Zhang
- John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, Mass; Suzhou Geno-truth Biotech Co, Ltd, Suzhou Industrial Park, Suzhou City, PR China
| | - Sunny S Po
- Section of Cardiovascular Diseases and Heart Rhythm Institute, University of Oklahoma Health Sciences Center, Oklahoma City, Okla.
| | - Huishan Wang
- Department of Cardiovascular Surgery, General Hospital of Northern Theater Command, Shenyang, PR China.
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Herhaus B, Ghassabei S, Petrowski K. Obesity: Heart Rate Variability during standardized psychosocial stress induction. Biol Psychol 2023; 178:108509. [PMID: 36736572 DOI: 10.1016/j.biopsycho.2023.108509] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2021] [Revised: 01/25/2023] [Accepted: 01/26/2023] [Indexed: 02/05/2023]
Abstract
Obesity is related to a higher risk of cardiovascular diseases (CVD). An altered stress reactivity of the parasympathetic nervous system (PNS) is a promising predictor of CVD and other negative health outcomes. Therefore, the aim of this study was to compare heart rate (HR) and heart rate variability parameters, root mean square successive differences (RMSSD) and power in the high frequency range 0.15-0.4 Hz (HF-HRV), of individuals with obesity and healthy weight controls during psychosocial stress induction. Thirty-four obese men and women (BMI: 33.80 ± 4.62 kg/m²), and thirty-four age- and gender-matched healthy weight controls (BMI: 22.29 ± 1.81 kg/m²) underwent the Trier Social Stress Test (TSST). Before, during, and after the TSST, their HR, RMSSD, and HF-HRV were measured. The individuals with obesity showed a lower stress reactivity in HR, and less stress recovery in RMSSD, compared to healthy weight controls. Obesity appears related to blunted HR reactivity, which is associated with CVD. In addition, impaired recovery of RMSSD also found in individuals with obesity may reflect health-damaging processes as well.
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Affiliation(s)
- Benedict Herhaus
- Medical Psychology and Medical Sociology, University Medical Center of the Johannes Gutenberg University of Mainz, Mainz, Germany.
| | - Shiwa Ghassabei
- Medical Psychology and Medical Sociology, University Medical Center of the Johannes Gutenberg University of Mainz, Mainz, Germany
| | - Katja Petrowski
- Medical Psychology and Medical Sociology, University Medical Center of the Johannes Gutenberg University of Mainz, Mainz, Germany
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15
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Preda A, Liberale L, Montecucco F. Imaging techniques for the assessment of adverse cardiac remodeling in metabolic syndrome. Heart Fail Rev 2022; 27:1883-1897. [PMID: 34796433 DOI: 10.1007/s10741-021-10195-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/11/2021] [Indexed: 12/23/2022]
Abstract
Metabolic syndrome (MetS) includes different metabolic conditions (i.e. abdominal obesity, impaired glucose tolerance, hypertriglyceridemia, decreased HDL cholesterol, and/or hypertension) that concour in the development of cardiovascular disease and diabetes. MetS individuals often show adverse cardiac remodeling and myocardial dysfunction even in the absence of overt coronary artery disease or valvular affliction. Diastolic impairment and hypertrophy are hallmarks of MetS-related cardiac remodeling and represent the leading cause of heart failure with preserved ejection fraction (HFpEF). Altered cardiomyocyte function, increased neurohormonal tone, interstitial fibrosis, coronary microvascular dysfunction, and a myriad of metabolic abnormalities have all been implicated in the development and progression of adverse cardiac remodeling related to MetS. However, despite the enormous amount of literature produced on this argument, HF remains a leading cause of morbidity and mortality in such population. The early detection of initial adverse cardiac remodeling would enable the optimal implementation of effective therapies aiming at preventing the progression of the disease to the symptomatic phase. Beyond conventional imaging techniques, such as echocardiography, cardiac tomography, and magnetic resonance, novel post-processing tools and techniques provide information on the biological processes that underlie metabolic heart disease. In this review, we summarize the pathophysiology of MetS-related cardiac remodeling and illustrate the relevance of state-of-the-art multimodality cardiac imaging to identify and quantify the degree of myocardial involvement, prognosticate long-term clinical outcome, and potentially guide therapeutic strategies.
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Affiliation(s)
| | - Luca Liberale
- First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, 6 viale Benedetto XV, 16132, Genoa, Italy
- Center for Molecular Cardiology, University of Zürich, Schlieren, Switzerland
- IRCCS Ospedale Policlinico San Martino Genoa-Italian Cardiovascular Network, Genoa, Italy
| | - Fabrizio Montecucco
- First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, 6 viale Benedetto XV, 16132, Genoa, Italy.
- IRCCS Ospedale Policlinico San Martino Genoa-Italian Cardiovascular Network, Genoa, Italy.
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16
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Musovic S, Komai AM, Said MK, Shrestha MM, Wu Y, Wernstedt Asterholm I, Olofsson CS. Noradrenaline and ATP regulate adiponectin exocytosis in white adipocytes: Disturbed adrenergic and purinergic signalling in obese and insulin-resistant mice. Mol Cell Endocrinol 2022; 549:111619. [PMID: 35337901 DOI: 10.1016/j.mce.2022.111619] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2021] [Revised: 02/26/2022] [Accepted: 03/10/2022] [Indexed: 01/19/2023]
Abstract
White adipocyte adiponectin exocytosis is triggered by cAMP and a concomitant increase of cytosolic Ca2+ potentiates its release. White adipose tissue is richly innervated by sympathetic nerves co-releasing noradrenaline (NA) and ATP, which may act on receptors in the adipocyte plasma membrane to increase cAMP via adrenergic receptors and Ca2+ via purinergic receptors. Here we determine the importance of NA and ATP for the regulation of white adipocyte adiponectin exocytosis, at the cellular and molecular level, and we specifically detail the ATP signalling pathway. We demonstrate that tyrosine hydroxylase (enzyme involved in catecholamine synthesis) is dramatically reduced in inguinal white adipose tissue (IWAT) isolated from mice with diet-induced obesity; this is associated with diminished levels of NA in IWAT and with a reduced ratio of high-molecular-weight (HMW) to total adiponectin in serum. Adiponectin exocytosis (measured as an increase in plasma membrane capacitance and as secreted product) is triggered by NA or ATP alone in cultured and primary mouse IWAT adipocytes, and enhanced by a combination of the two secretagogues. The ATP-induced adiponectin exocytosis is largely Ca2+-dependent and activated via purinergic P2Y2 receptors (P2Y2Rs) and the Gq11/PLC pathway. Adiponectin release induced by the nucleotide is abrogated in adipocytes isolated from obese and insulin-resistant mice, and this is associated with ∼70% reduced abundance of P2Y2Rs. The NA-triggered adiponectin exocytosis is likewise abolished in "obese adipocytes", concomitant with a 50% lower gene expression of beta 3 adrenergic receptors (β3ARs). An increase in intracellular Ca2+ is not required for the NA-stimulated adiponectin secretion. Collectively, our data suggest that sympathetic innervation is a principal regulator of adiponectin exocytosis and that disruptions of this control are associated with the obesity-associated reduction of circulating levels of HMW/total adiponectin.
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Affiliation(s)
- Saliha Musovic
- Department of Physiology/Metabolic Physiology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Medicinaregatan 11, SE-405 30, Göteborg, Sweden
| | - Ali M Komai
- Department of Physiology/Metabolic Physiology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Medicinaregatan 11, SE-405 30, Göteborg, Sweden
| | - Marina Kalds Said
- Department of Physiology/Metabolic Physiology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Medicinaregatan 11, SE-405 30, Göteborg, Sweden
| | - Man Mohan Shrestha
- Department of Physiology/Metabolic Physiology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Medicinaregatan 11, SE-405 30, Göteborg, Sweden
| | - Yanling Wu
- Department of Physiology/Metabolic Physiology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Medicinaregatan 11, SE-405 30, Göteborg, Sweden
| | - Ingrid Wernstedt Asterholm
- Department of Physiology/Metabolic Physiology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Medicinaregatan 11, SE-405 30, Göteborg, Sweden
| | - Charlotta S Olofsson
- Department of Physiology/Metabolic Physiology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Medicinaregatan 11, SE-405 30, Göteborg, Sweden.
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17
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Singh U, Jiang J, Saito K, Toth BA, Dickey JE, Rodeghiero SR, Deng Y, Deng G, Xue B, Zhu Z, Zingman LV, Geerling JC, Cui H. Neuroanatomical organization and functional roles of PVN MC4R pathways in physiological and behavioral regulations. Mol Metab 2022; 55:101401. [PMID: 34823066 PMCID: PMC8689242 DOI: 10.1016/j.molmet.2021.101401] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Revised: 11/04/2021] [Accepted: 11/17/2021] [Indexed: 11/23/2022] Open
Abstract
OBJECTIVE The paraventricular nucleus of hypothalamus (PVN), an integrative center in the brain, orchestrates a wide range of physiological and behavioral responses. While the PVN melanocortin 4 receptor (MC4R) signaling (PVNMC4R+) is involved in feeding regulation, the neuroanatomical organization of PVNMC4R+ connectivity and its role in other physiological regulations are incompletely understood. Here we aimed to better characterize the input-output organization of PVNMC4R+ neurons and test their physiological functions beyond feeding. METHODS Using a combination of viral tools, we mapped PVNMC4R+ circuits and tested the effects of chemogenetic activation of PVNMC4R+ neurons on thermoregulation, cardiovascular control, and other behavioral responses beyond feeding. RESULTS We found that PVNMC4R+ neurons innervate many different brain regions that are known to be important not only for feeding but also for neuroendocrine and autonomic control of thermoregulation and cardiovascular function, including but not limited to the preoptic area, median eminence, parabrachial nucleus, pre-locus coeruleus, nucleus of solitary tract, ventrolateral medulla, and thoracic spinal cord. Contrary to these broad efferent projections, PVNMC4R+ neurons receive monosynaptic inputs mainly from other hypothalamic nuclei (preoptic area, arcuate and dorsomedial hypothalamic nuclei, supraoptic nucleus, and premammillary nucleus), the circumventricular organs (subfornical organ and vascular organ of lamina terminalis), the bed nucleus of stria terminalis, and the parabrachial nucleus. Consistent with their broad efferent projections, chemogenetic activation of PVNMC4R+ neurons not only suppressed feeding but also led to an apparent increase in heart rate, blood pressure, and brown adipose tissue temperature. These physiological changes accompanied acute transient hyperactivity followed by hypoactivity and resting-like behavior. CONCLUSIONS Our results elucidate the neuroanatomical organization of PVNMC4R+ circuits and shed new light on the roles of PVNMC4R+ pathways in autonomic control of thermoregulation, cardiovascular function, and biphasic behavioral activation.
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Affiliation(s)
- Uday Singh
- Department of Neuroscience and Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IA, United States
| | - Jingwei Jiang
- Department of Neuroscience and Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IA, United States
| | - Kenji Saito
- Department of Neuroscience and Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IA, United States
| | - Brandon A Toth
- Department of Neuroscience and Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IA, United States
| | - Jacob E Dickey
- Department of Neuroscience and Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IA, United States
| | - Samuel R Rodeghiero
- Department of Neuroscience and Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IA, United States
| | - Yue Deng
- Department of Neuroscience and Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IA, United States
| | - Guorui Deng
- Department of Neuroscience and Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IA, United States
| | - Baojian Xue
- Department of Psychological and Brain Sciences, University of Iowa, Iowa City, IA, United States
| | - Zhiyong Zhu
- Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA, United States
| | - Leonid V Zingman
- Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA, United States
| | - Joel C Geerling
- Department of Neurology, University of Iowa Carver College of Medicine, Iowa City, IA, United States; Iowa Neuroscience Institute, University of Iowa Carver College of Medicine, Iowa City, IA, United States
| | - Huxing Cui
- Department of Neuroscience and Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IA, United States; F.O.E. Diabetes Research Center, University of Iowa Carver College of Medicine, Iowa City, IA, United States; Iowa Neuroscience Institute, University of Iowa Carver College of Medicine, Iowa City, IA, United States; Obesity Research and Educational Initiative, University of Iowa Carver College of Medicine, Iowa City, IA, United States.
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18
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Repeated Oral Administration of Flavan-3-ols Induces Browning in Mice Adipose Tissues through Sympathetic Nerve Activation. Nutrients 2021; 13:nu13124214. [PMID: 34959764 PMCID: PMC8707158 DOI: 10.3390/nu13124214] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2021] [Revised: 11/19/2021] [Accepted: 11/22/2021] [Indexed: 12/13/2022] Open
Abstract
We previously found increases in uncoupling protein (Ucp)-1 transcription in brown adipose tissue (BAT) of mice following a single oral dose of flavan 3-ol (FL)s, a fraction of catechins and procyanidins. It was confirmed that these changes were totally reduced by co-treatment of adrenaline blockers. According to these previous results, FLs possibly activate sympathetic nervous system (SNS). In this study, we confirmed the marked increase in urinary catecholamine (CA) s projecting SNS activity following a single dose of 50 mg/kg FLs. In addition, we examined the impact of the repeated administration of 50 mg/kg FLs for 14 days on adipose tissues in mice. In BAT, FLs tended to increase the level of Ucp-1 along with significant increase of thermogenic transcriptome factors expressions, such as peroxisome proliferator-activated receptor γ coactivator (PGC)-1α and PR domain-containing (PRDM)1. Expression of browning markers, CD137 and transmembrane protein (TMEM) 26, in addition to PGC-1α were increased in epididymal adipose (eWAT) by FLs. A multilocular morphology with cell size reduction was shown in the inguinal adipose (iWAT), together with increasing the level of Ucp-1 by FLs. These results exert that FLs induce browning in adipose, and this change is possibly produced by the activation of the SNS.
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19
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Evaluation of Normal Adrenal Gland Volume and Morphometry and Relationship with Waist Circumference in an Adult Population Using Multidetector Computed Tomography. SISLI ETFAL HASTANESI TIP BULTENI 2021; 55:333-338. [PMID: 34712074 PMCID: PMC8526233 DOI: 10.14744/semb.2021.96462] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/21/2021] [Accepted: 06/27/2021] [Indexed: 12/15/2022]
Abstract
Objectives: This study aims to determine the normal range of values of the right, left, and total volume and shape of the adrenal gland (AG) and to evaluate its relationship with gender, age, height, weight, body mass index (BMI), and waist circumference (WC) in multidetector computed tomography (MDCT) images. Methods: The study included 115 MDCT scans, of which 56 were men and 59 were women. For volume measurement, the outlines of the AG were drawn semi-automatically for all patients. Then, collecting the area in each slice, the volumes were automatically measured. The intraclass correlation coefficient (ICC) test was used to analyze intraobserver reliability for repeated measurements with a 95% confidence interval. Participant’s age, gender, weight, height, BMI, and WC were obtained. p<0.05 was considered statistically significant. Results: The mean age of participants was 49.5±17.7 (19–81). The average right AGV (RAGV), left AGV (LAGV), and total AGV were 3.47±1.33, 4.77±1.33, and 8.25±2.74, respectively. The ICC values for all measurements were >0.80–0.90, indicating good and excellent agreement. LAGV was measured as higher than the RAGV. A positive moderate correlation of the AGVs with BMI and WC was observed. Conclusion: The increase in BMI and WC, which are indicators of obesity, correlates with the increase in AGV, we think that the findings will be valuable in evaluating the pathophysiology of the hypothalamic-pituitary-adrenal axis.
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Macut D, Ognjanović S, Ašanin M, Krljanac G, Milenković T. Metabolic syndrome and myocardial infarction in women. Curr Pharm Des 2021; 27:3786-3794. [PMID: 34115582 DOI: 10.2174/1381612827666210610114029] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2021] [Accepted: 04/29/2021] [Indexed: 11/22/2022]
Abstract
Metabolic syndrome (MetS) represents a cluster of metabolic disorders that arise from insulin resistance (IR) and adipose tissue dysfunction. As a consequence, there is an increased risk for type 2 diabetes mellitus and atherosclerotic cardiovascular disease (CVD). MetS is associated with a 2-fold increase in cardiovascular outcomes. Earlier population analyses showed a lower prevalence of MetS in women (23.9%) in comparison to men (27.8%), while later analyses suggested significantly reduced difference due to an increase in prevalence in women aged between 20 and 39. However, the prevalence of MetS in specific populations of women, such as in women with polycystic ovary syndrome, ranges from 16% to almost 50% in some geographic regions. Abdominal fat accumulation and IR syndrome are recognized as the most important factors in the pathogenesis of MetS. After menopause, a decline in insulin sensitivity corresponds to an increase in fat mass, circulating fatty acids, low-density lipoproteins, and triglycerides. Prevalence of MetS in acute coronary syndrome (ACS) is significantly more present in women (55.9%-66.3%) than in men (40.2%-47.3%) in different cohorts. Younger women with ACS had a higher mortality rate than younger men. Acute myocardial infarction (AMI) remains a leading cause of death in aging women. Women with AMI have significantly higher rates of prior congestive heart failure, hypertension history, and diabetes. The role of androgens in CVD pathogenesis in women has not yet been clarified. The current review aims to give an insight into the role of MetS components and inflammation for the development of atherosclerosis, CVD, and AMI in women.
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Affiliation(s)
- Djuro Macut
- Clinic for Endocrinology, Diabetes, and Diseases of Metabolism, University Clinical Center of Serbia, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
| | - Sanja Ognjanović
- Clinic for Endocrinology, Diabetes, and Diseases of Metabolism, University Clinical Center of Serbia, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
| | - Milika Ašanin
- Clinic for Cardiology, University Clinical Center of Serbia, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
| | - Gordana Krljanac
- Clinic for Cardiology, University Clinical Center of Serbia, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
| | - Tatjana Milenković
- University Clinic of Endocrinology, Diabetes and Metabolic Disorders, Medical Faculty, University of Skopje, Skopje, Macedonia
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21
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Zhong B, Ma S, Wang DH. Ablation of TRPV1 Abolishes Salicylate-Induced Sympathetic Activity Suppression and Exacerbates Salicylate-Induced Renal Dysfunction in Diet-Induced Obesity. Cells 2021; 10:1234. [PMID: 34069822 PMCID: PMC8157242 DOI: 10.3390/cells10051234] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2021] [Revised: 05/01/2021] [Accepted: 05/14/2021] [Indexed: 11/24/2022] Open
Abstract
Sodium salicylate (SA), a cyclooxygenase inhibitor, has been shown to increase insulin sensitivity and to suppress inflammation in obese patients and animal models. Transient receptor potential vanilloid 1 (TRPV1) is a nonselective cation channel expressed in afferent nerve fibers. Cyclooxygenase-derived prostaglandins are involved in the activation and sensitization of TRPV1. This study tested whether the metabolic and renal effects of SA were mediated by the TRPV1 channel. Wild-type (WT) and TRPV1-/- mice were fed a Western diet (WD) for 4 months and received SA infusion (120mg/kg/day) or vehicle for the last 4 weeks of WD feeding. SA treatment significantly increased blood pressure in WD-fed TRPV1-/- mice (p < 0.05) but not in WD-fed WT mice. Similarly, SA impaired renal blood flow in TRPV1-/- mice (p < 0.05) but not in WT mice. SA improved insulin and glucose tolerance in both WT and TRPV1-/- mice on WD (all p < 0.05). In addition, SA reduced renal p65 and urinary prostaglandin E2, prostaglandin F1α, and interleukin-6 in both WT and TRPV1-/- mice (all p < 0.05). SA decreased urine noradrenaline levels, increased afferent renal nerve activity, and improved baroreflex sensitivity in WT mice (all p < 0.05) but not in TRPV1-/- mice. Importantly, SA increased serum creatinine and urine kidney injury molecule-1 levels and decreased the glomerular filtration rate in obese WT mice (all p < 0.05), and these detrimental effects were significantly exacerbated in obese TRPV1-/- mice (all p < 0.05). Lastly, SA treatment increased urine albumin levels in TRPV1-/- mice (p < 0.05) but not in WT mice. Taken together, SA-elicited metabolic benefits and anti-inflammatory effects are independent of TRPV1, while SA-induced sympathetic suppression is dependent on TRPV1 channels. SA-induced renal dysfunction is dependent on intact TRPV1 channels. These findings suggest that SA needs to be cautiously used in patients with obesity or diabetes, as SA-induced renal dysfunction may be exacerbated due to impaired TRPV1 in obese and diabetic patients.
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Affiliation(s)
- Beihua Zhong
- Division of Nanomedicine and Molecular Intervention, Department of Medicine, Michigan State University, East Lansing, MI 48824, USA; (B.Z.); (S.M.)
| | - Shuangtao Ma
- Division of Nanomedicine and Molecular Intervention, Department of Medicine, Michigan State University, East Lansing, MI 48824, USA; (B.Z.); (S.M.)
| | - Donna H. Wang
- Division of Nanomedicine and Molecular Intervention, Department of Medicine, Michigan State University, East Lansing, MI 48824, USA; (B.Z.); (S.M.)
- Neuroscience Program, Michigan State University, East Lansing, MI 48824, USA
- Cell and Molecular Biology Program, Michigan State University, East Lansing, MI 48824, USA
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Ajibewa TA, Adams TA, Gill AK, Mazin LE, Gerras JE, Hasson RE. Stress coping strategies and stress reactivity in adolescents with overweight/obesity. Stress Health 2021; 37:243-254. [PMID: 32978994 DOI: 10.1002/smi.2987] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2019] [Revised: 07/11/2020] [Accepted: 09/14/2020] [Indexed: 11/07/2022]
Abstract
This study explored the associations between the frequency and effectiveness of habitual stress coping strategies on physiological and psychological stress responses to an acute laboratory stressor in adolescents with overweight/obesity (51 adolescents; 47% female; ages 14-19 years). Coping strategies were assessed using the Schoolager's Coping Strategies Inventory. Acute physiological stress responses were measured as salivary cortisol and α-amylase output during the Trier Social Stress Test and during a control condition. Acute psychological stress was measured using a Likert-type scale, and systolic blood pressure (SBP) and heart rate were measured at baseline. Results revealed that higher coping effectiveness was associated with lower log-based α-amylase during the stress (β = -0.025, p = 0.018) and control (β = -0.030, p = 0.005) conditions, but not with cortisol across either condition (all ps > 0.05). SBP moderated the association between coping effectiveness and α-amylase during the stress condition, with higher coping effectiveness associated with lower α-amylase only among individuals with lower SBP (β = 0.002, p = 0.027). Coping frequency was not associated with cortisol responses, neither was habitual stress coping strategies associated with psychological stress (all ps > 0.05). These findings provide preliminary evidence that effective use of stress coping strategies may provide a dampening effect on sympathetic activity in an at-risk adolescent population.
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Affiliation(s)
- Tiwaloluwa A Ajibewa
- School of Kinesiology, University of Michigan, Ann Arbor, Michigan, USA.,Childhood Disparities Research Laboratory, University of Michigan, Ann Arbor, Michigan, USA
| | - Tessa A Adams
- Childhood Disparities Research Laboratory, University of Michigan, Ann Arbor, Michigan, USA
| | - Amaanat K Gill
- Childhood Disparities Research Laboratory, University of Michigan, Ann Arbor, Michigan, USA
| | - Lauren E Mazin
- Childhood Disparities Research Laboratory, University of Michigan, Ann Arbor, Michigan, USA
| | - Julia E Gerras
- Childhood Disparities Research Laboratory, University of Michigan, Ann Arbor, Michigan, USA
| | - Rebecca E Hasson
- School of Kinesiology, University of Michigan, Ann Arbor, Michigan, USA.,Childhood Disparities Research Laboratory, University of Michigan, Ann Arbor, Michigan, USA.,School of Public Health, University of Michigan, Ann Arbor, Michigan, USA
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23
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Sangaleti CT, Katayama KY, De Angelis K, Lemos de Moraes T, Araújo AA, Lopes HF, Camacho C, Bortolotto LA, Michelini LC, Irigoyen MC, Olofsson PS, Barnaby DP, Tracey KJ, Pavlov VA, Consolim Colombo FM. The Cholinergic Drug Galantamine Alleviates Oxidative Stress Alongside Anti-inflammatory and Cardio-Metabolic Effects in Subjects With the Metabolic Syndrome in a Randomized Trial. Front Immunol 2021; 12:613979. [PMID: 33776997 PMCID: PMC7991724 DOI: 10.3389/fimmu.2021.613979] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2020] [Accepted: 02/08/2021] [Indexed: 12/13/2022] Open
Abstract
Background: The metabolic syndrome (MetS) is an obesity-associated disorder of pandemic proportions and limited treatment options. Oxidative stress, low-grade inflammation and altered neural autonomic regulation, are important components and drivers of pathogenesis. Galantamine, an acetylcholinesterase inhibitor and a cholinergic drug that is clinically-approved (for Alzheimer's disease) has been implicated in neural cholinergic regulation of inflammation in several conditions characterized with immune and metabolic derangements. Here we examined the effects of galantamine on oxidative stress in parallel with inflammatory and cardio-metabolic parameters in subjects with MetS. Trial Design and Methods: The effects of galantamine treatment, 8 mg daily for 4 weeks or placebo, followed by 16 mg daily for 8 weeks or placebo were studied in randomly assigned subjects with MetS (n = 22 per group) of both genders. Oxidative stress, including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase activities, lipid and protein peroxidation, and nitrite levels were analyzed before and at the end of the treatment. In addition, plasma cytokine and adipokine levels, insulin resistance (HOMA-IR) and other relevant cardio-metabolic indices were analyzed. Autonomic regulation was also examined by heart rate variability (HRV) before treatment, and at every 4 weeks of treatment. Results: Galantamine treatment significantly increased antioxidant enzyme activities, including SOD [+1.65 USOD/mg protein, [95% CI 0.39-2.92], P = 0.004] and CAT [+0.93 nmol/mg, [95% CI 0.34-1.51], P = 0.01], decreased lipid peroxidation [thiobarbituric acid reactive substances [log scale 0.72 pmol/mg, [95% CI 0.46-1.07], P = 0.05], and systemic nitrite levels [log scale 0.83 μmol/mg protein, [95% CI 0.57-1.20], P = 0.04] compared with placebo. In addition, galantamine significantly alleviated the inflammatory state and insulin resistance, and decreased the low frequency/high frequency ratio of HRV, following 8 and 12 weeks of drug treatment. Conclusion: Low-dose galantamine alleviates oxidative stress, alongside beneficial anti-inflammatory, and metabolic effects, and modulates neural autonomic regulation in subjects with MetS. These findings are of considerable interest for further studies with the cholinergic drug galantamine to ameliorate MetS.
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Affiliation(s)
- Carine Teles Sangaleti
- Hypertension Unit, University of São Paulo (USP), São Paulo, Brazil
- Postgraduate Program in Health Science, Midwestern State University (UNICENTRO), Paraná, Brazil
| | - Keyla Yukari Katayama
- Nursing Department Graduate Program in Nanosciences and Biosciences, Nove de Julho University (UNINOVE), São Paulo, Brazil
| | - Kátia De Angelis
- Nursing Department Graduate Program in Nanosciences and Biosciences, Nove de Julho University (UNINOVE), São Paulo, Brazil
- Department of Physiology, Federal University of São Paulo (UNIFESP), São Paulo, Brazil
| | - Tércio Lemos de Moraes
- Nursing Department Graduate Program in Nanosciences and Biosciences, Nove de Julho University (UNINOVE), São Paulo, Brazil
| | | | - Heno F. Lopes
- Hypertension Unit, University of São Paulo (USP), São Paulo, Brazil
- Nursing Department Graduate Program in Nanosciences and Biosciences, Nove de Julho University (UNINOVE), São Paulo, Brazil
| | - Cleber Camacho
- Nursing Department Graduate Program in Nanosciences and Biosciences, Nove de Julho University (UNINOVE), São Paulo, Brazil
| | | | - Lisete Compagno Michelini
- Biomedical Sciences Institute Department of Physiology and Biophysics, University of São Paulo (USP), São Paulo, Brazil
| | | | - Peder S. Olofsson
- Laboratory of Immunobiology, Department of Medicine, Center for Bioelectronic Medicine, Karolinska Institutet, Stockholm, Sweden
- The Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY, United States
| | - Douglas P. Barnaby
- The Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY, United States
| | - Kevin J. Tracey
- The Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY, United States
| | - Valentin A. Pavlov
- The Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY, United States
| | - Fernanda Marciano Consolim Colombo
- Hypertension Unit, University of São Paulo (USP), São Paulo, Brazil
- Nursing Department Graduate Program in Nanosciences and Biosciences, Nove de Julho University (UNINOVE), São Paulo, Brazil
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24
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Oxidative Stress, Plant Natural Antioxidants, and Obesity. Int J Mol Sci 2021; 22:ijms22041786. [PMID: 33670130 PMCID: PMC7916866 DOI: 10.3390/ijms22041786] [Citation(s) in RCA: 217] [Impact Index Per Article: 54.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Revised: 02/07/2021] [Accepted: 02/08/2021] [Indexed: 02/07/2023] Open
Abstract
Oxidative stress is important in the pathophysiology of obesity, altering regulatory factors of mitochondrial activity, modifying the concentration of inflammation mediators associated with a large number and size of adipocytes, promoting lipogenesis, stimulating differentiation of preadipocytes to mature adipocytes, and regulating the energy balance in hypothalamic neurons that control appetite. This review discusses the participation of oxidative stress in obesity and the important groups of compounds found in plants with antioxidant properties, which include (a) polyphenols such as phenolic acids, stilbenes, flavonoids (flavonols, flavanols, anthocyanins, flavanones, flavones, flavanonols, and isoflavones), and curcuminoids (b) carotenoids, (c) capsaicinoids and casinoids, (d) isothiocyanates, (e) catechins, and (f) vitamins. Examples are analyzed, such as resveratrol, quercetin, curcumin, ferulic acid, phloretin, green tea, Hibiscus Sabdariffa, and garlic. The antioxidant activities of these compounds depend on their activities as reactive oxygen species (ROS) scavengers and on their capacity to prevent the activation of NF-κB (nuclear factor κ-light-chain-enhancer of activated B cells), and reduce the expression of target genes, including those participating in inflammation. We conclude that natural compounds have therapeutic potential for diseases mediated by oxidative stress, particularly obesity. Controlled and well-designed clinical trials are still necessary to better know the effects of these compounds.
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25
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Gao L, Gaba A, Cui L, Yang HW, Saxena R, Scheer FAJL, Akeju O, Rutter MK, Lo MT, Hu K, Li P. Resting Heartbeat Complexity Predicts All-Cause and Cardiorespiratory Mortality in Middle- to Older-Aged Adults From the UK Biobank. J Am Heart Assoc 2021; 10:e018483. [PMID: 33461311 PMCID: PMC7955428 DOI: 10.1161/jaha.120.018483] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
Background Spontaneous heart rate fluctuations contain rich information related to health and illness in terms of physiological complexity, an accepted indicator of plasticity and adaptability. However, it is challenging to make inferences on complexity from shorter, more practical epochs of data. Distribution entropy (DistEn) is a recently introduced complexity measure that is designed specifically for shorter duration heartbeat recordings. We hypothesized that reduced DistEn predicted increased mortality in a large population cohort. Method and Results The prognostic value of DistEn was examined in 7631 middle‐older–aged UK Biobank participants who had 2‐minute resting ECGs conducted (mean age, 59.5 years; 60.4% women). During a median follow‐up period of 7.8 years, 451 (5.9%) participants died. In Cox proportional hazards models with adjustment for demographics, lifestyle factors, physical activity, cardiovascular risks, and comorbidities, for each 1‐SD decrease in DistEn, the risk increased by 36%, 56%, and 73% for all‐cause, cardiovascular, and respiratory disease–related mortality, respectively. These effect sizes were equivalent to the risk of death from being >5 years older, having been a former smoker, or having diabetes mellitus. Lower DistEn was most predictive of death in those <55 years with a prior myocardial infarction, representing an additional 56% risk for mortality compared with older participants without prior myocardial infarction. These observations remained after controlling for traditional mortality predictors, resting heart rate, and heart rate variability. Conclusions Resting heartbeat complexity from short, resting ECGs was independently associated with mortality in middle‐ to older‐aged adults. These risks appear most pronounced in middle‐aged participants with prior MI, and may uniquely contribute to mortality risk screening.
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Affiliation(s)
- Lei Gao
- Department of Anesthesia Critical Care and Pain Medicine Massachusetts General HospitalHarvard Medical School Boston MA.,Medical Biodynamics Program Brigham and Women's Hospital Boston MA
| | - Arlen Gaba
- Medical Biodynamics Program Brigham and Women's Hospital Boston MA
| | - Longchang Cui
- Medical Biodynamics Program Brigham and Women's Hospital Boston MA
| | - Hui-Wen Yang
- Medical Biodynamics Program Brigham and Women's Hospital Boston MA
| | - Richa Saxena
- Department of Anesthesia Critical Care and Pain Medicine Massachusetts General HospitalHarvard Medical School Boston MA.,Broad Institute of MIT and Harvard Cambridge MA.,Center for Genomic Medicine Massachusetts General Hospital Boston MA
| | - Frank A J L Scheer
- Broad Institute of MIT and Harvard Cambridge MA.,Division of Sleep Medicine Harvard Medical School Boston MA
| | - Oluwaseun Akeju
- Department of Anesthesia Critical Care and Pain Medicine Massachusetts General HospitalHarvard Medical School Boston MA
| | - Martin K Rutter
- Division of Diabetes Endocrinology & Gastroenterology The University of Manchester Manchester UK
| | - Men-Tzung Lo
- Institute of Translational and Interdisciplinary Medicine and Department of Biomedical Sciences and Engineering National Central University Taoyuan Taiwan
| | - Kun Hu
- Medical Biodynamics Program Brigham and Women's Hospital Boston MA.,Division of Sleep Medicine Harvard Medical School Boston MA
| | - Peng Li
- Medical Biodynamics Program Brigham and Women's Hospital Boston MA.,Division of Sleep Medicine Harvard Medical School Boston MA
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26
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Lopes H, Egan B. Visceral adiposity syndrome and cardiometabolism. SCRIPTA MEDICA 2021. [DOI: 10.5937/scriptamed52-32717] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/02/2022] Open
Abstract
The distribution of fat in the human body is related to hemodynamic and metabolic homeostasis. Brown fat is inversely related to body mass index and is associated with a lower probability of developing diabetes. Beige adipose tissue shares some functional characteristics with brown adipose tissue. White adipose tissue constitutes the majority of the fatty tissue and is mainly distributed in the subcutaneous and abdominal cavity. Intra-abdominal white fat has gained prominence in recent years for its association with cardiovascular risk factors and higher cardiovascular mortality. This review article discusses the human adaptation in the environment, a sympathovagal and hypothalamic-pituitary-adrenal imbalance as a possible cause of increased visceral adiposity and its consequences on cardiometabolism.
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27
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Safaryan AS, Sargsyan VD. Sympathetic hyperactivity in patients with hypertension: pathogenesis and treatment. Part I. КАРДИОВАСКУЛЯРНАЯ ТЕРАПИЯ И ПРОФИЛАКТИКА 2020. [DOI: 10.15829/1728-8800-2020-2693] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023] Open
Abstract
The article is devoted to the influence of sympathetic nervous system (SNS) on the cardiovascular system. Influence of SNS activity on the blood pressure level and the pathogenesis of hypertension development, as well as the effect of SNS on many biochemical and metabolic parameters playing a key role in the development of metabolic syndrome and hypertension are considered. Possible mechanisms of action of various methods that reduce the SNS activity, restore the function of autonomic nervous system and normalize the cardiovascular system and blood pressure are considered.
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Affiliation(s)
- A. S. Safaryan
- National Research Center for Therapy and Preventive Medicine
| | - V. D. Sargsyan
- National Research Center for Therapy and Preventive Medicine
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28
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Effect of Neudesin Neurotrophic Factor on Differentiation of Bovine Preadipocytes and Myoblasts in a Co-Culture System. Animals (Basel) 2020; 11:ani11010034. [PMID: 33375362 PMCID: PMC7823575 DOI: 10.3390/ani11010034] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2020] [Revised: 12/17/2020] [Accepted: 12/23/2020] [Indexed: 11/17/2022] Open
Abstract
Simple Summary Marbling beef refers to the red and white beef formed by depositing fat between muscle fibers, and “marbling” is an important factor affecting beef quality. Therefore, we established a co-culture system of adipocytes and myocytes to mimic the microenvironment of marbling beef in vivo. However, Neudesin neurotrophic factor (NENF) was not detected in the co-culture system, but was detected in both adipocytes and myoblasts cultured separately. Further studies revealed that NENF knockdown inhibits adipogenesis and promotes myogenesis in separately cultured preadipocytes and myoblasts. However, because the monoculture system does not include the interaction of bovine adipocytes and myoblasts in the formation of marbling beef, in this study we investigated the effect of recombinant protein NENF on the differentiation of adipocytes and myoblasts in the co-culture system. The addition of NENF inhibited the formation of lipid droplets in co-cultured adipocytes but had no significant effect on myotube formation. These results were different from, and even conflicted with, those in the monocultures, which suggested that regulation of NENF expression in the same cell type changed along with the cell microenvironment and the molecular mechanism of marbling beef formation cannot be fully revealed through studies on the monoculture system. Abstract In this study, we successfully established a co-culture system of bovine preadipocytes and myoblasts to explore the effect of exogenous addition of Neudesin neurotrophic factor (NENF) recombinant protein on the differentiation of adipocytes and myoblasts in co-culture. The optimal concentration of NENF recombinant protein was 100 pg/mL. NENF promoted the differentiation of bovine preadipocytes and inhibited the differentiation of bovine myoblasts when the cells were cultured separately. After adding NENF recombinant protein to the co-culture system, the accumulation of lipid droplets in bovine preadipocytes decreased, but the differentiation of bovine myoblasts did not change significantly. The results of real-time quantitative PCR (RT-qPCR) and Western blot showed that the expression levels of adipogenesis-related factors such as PPARγ, FABP4 and FASN were significantly down-regulated at the mRNA and protein levels in adipocytes, while myogenic marker genes such as MYOD1, MYOG and MYHC had no significant changes at the mRNA or protein levels in myoblasts. This differs from, and potentially conflicts with, the monoculture system, where NENF expression in each cell type changed with the cell microenvironment. Consequently, the molecular mechanism of marbling beef formation cannot be fully revealed using monocultures of adipocytes or myocytes.
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29
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Diabesity: the combined burden of obesity and diabetes on heart disease and the role of imaging. Nat Rev Cardiol 2020; 18:291-304. [PMID: 33188304 DOI: 10.1038/s41569-020-00465-5] [Citation(s) in RCA: 169] [Impact Index Per Article: 33.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/05/2020] [Indexed: 02/06/2023]
Abstract
Diabesity is a term used to describe the combined adverse health effects of obesity and diabetes mellitus. The worldwide dual epidemic of obesity and type 2 diabetes is an important public health issue. Projections estimate a sixfold increase in the number of adults with obesity in 40 years and an increase in the number of individuals with diabetes to 642 million by 2040. Increased adiposity is the strongest risk factor for developing diabetes. Early detection of the effects of diabesity on the cardiovascular system would enable the optimal implementation of effective therapies that prevent atherosclerosis progression, cardiac remodelling, and the resulting ischaemic heart disease and heart failure. Beyond conventional imaging techniques, such as echocardiography, CT and cardiac magnetic resonance, novel post-processing tools and techniques provide information on the biological processes that underlie metabolic heart disease. In this Review, we summarize the effects of obesity and diabetes on myocardial structure and function and illustrate the use of state-of-the-art multimodality cardiac imaging to elucidate the pathophysiology of myocardial dysfunction, prognosticate long-term clinical outcomes and potentially guide treatment strategies.
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30
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Abstract
Environmental optimization of both the home and the veterinary clinic not only is important for promoting good emotional and cognitive health for domestic cats but also contributes to the promotion of good physical health. All 3 aspects of the feline health triad are interconnected. Inappropriate learning can occur resulting in perpetuation of behavioral responses and confirmation of emotional associations. In addition, the physiologic responses to compromised emotions and sustained negative emotional motivation can be involved in the triggering, maintenance, and increased significance of a range of physical health issues, including urinary tract, gastrointestinal, and dermatologic disease and chronic pain.
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Affiliation(s)
- Sarah Heath
- University of Liverpool School of Veterinary Science, Liverpool, UK; Behavioural Referrals Veterinary Practice, 10 Rushton Drive, Upton CH2 1RE, Chester, UK.
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31
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Cross A, Naughton F, Sheffield D. What is the role of stress cardiovascular reactivity in health behaviour change? A systematic review, meta-analysis and research agenda. Psychol Health 2020; 36:1021-1040. [PMID: 32998581 DOI: 10.1080/08870446.2020.1825714] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
OBJECTIVE The stress reactivity hypothesis posits that the extremes of exaggerated and low or blunted cardiovascular reactivity (CVR) to stress may lead to adverse health outcomes via psychophysiological pathways. A potential indirect pathway between CVR and disease outcomes is through health-related behaviour and behaviour change. However, this is a less well understood pathway. Design: A registered systematic review was undertaken to determine the association between cardiovascular reactivity (CVR) and health behaviour change, as well as identify mediators and moderators. Eight papers that met the inclusion criteria, focused on smoking cessation and weight loss, were identified. Results: Pooling data from studies exploring the prospective relationship between CVR (as systolic blood pressure) and smoking cessation found that exaggerated CVR was associated with smoking relapse (Hedges' g = 0.39, SE = 0.00, 95% CI 0.38 - 0.40, p < .001; I2 = 0%; N = 257) but did not find evidence that CVR responses were associated with changes in weight. In order to advance our understanding of reactivity as a modifiable determinant of health behaviour change, our review recommends exploring the association between CVR and other health behaviours, to determine the influence of blunted reactivity versus low motivational effort identify mediators and moderators and determine the focus of interventions.
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Affiliation(s)
- Ainslea Cross
- School of Psychology, University of Derby, Derby, UK
| | - Felix Naughton
- School of Health Sciences, University of East Anglia, Norwich, UK
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32
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Kim LJ, Polotsky VY. Carotid Body and Metabolic Syndrome: Mechanisms and Potential Therapeutic Targets. Int J Mol Sci 2020; 21:E5117. [PMID: 32698380 PMCID: PMC7404212 DOI: 10.3390/ijms21145117] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2020] [Revised: 07/11/2020] [Accepted: 07/16/2020] [Indexed: 12/19/2022] Open
Abstract
The carotid body (CB) is responsible for the peripheral chemoreflex by sensing blood gases and pH. The CB also appears to act as a peripheral sensor of metabolites and hormones, regulating the metabolism. CB malfunction induces aberrant chemosensory responses that culminate in the tonic overactivation of the sympathetic nervous system. The sympatho-excitation evoked by CB may contribute to the pathogenesis of metabolic syndrome, inducing systemic hypertension, insulin resistance and sleep-disordered breathing. Several molecular pathways are involved in the modulation of CB activity, and their pharmacological manipulation may lead to overall benefits for cardiometabolic diseases. In this review, we will discuss the role of the CB in the regulation of metabolism and in the pathogenesis of the metabolic dysfunction induced by CB overactivity. We will also explore the potential pharmacological targets in the CB for the treatment of metabolic syndrome.
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Affiliation(s)
- Lenise J. Kim
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD 21224, USA;
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33
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Drouin JS, Pfalzer L, Shim JM, Kim SJ. Comparisons between Manual Lymph Drainage, Abdominal Massage, and Electrical Stimulation on Functional Constipation Outcomes: A Randomized, Controlled Trial. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2020; 17:ijerph17113924. [PMID: 32492920 PMCID: PMC7313091 DOI: 10.3390/ijerph17113924] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/19/2020] [Revised: 05/28/2020] [Accepted: 05/29/2020] [Indexed: 12/21/2022]
Abstract
BACKGROUND Evidence supports abdominal massage (AM) or electrical stimulation (ES) as effective in treating functional constipation (FC). Manual lymph drainage (MLD) may also be beneficial, however, it was not previously investigated or compared to ES and AM. METHODS Sixteen college-aged males and 36 females were recruited. Participants were randomly assigned to MLD, AM or ES. Heart rate variability (HRV) measures for total power (TP), high frequency (HF), low frequency and LF/HF ratio assessed ANS outcomes. state-trait anxiety inventory (STAI) and stress response inventory (SRI) assessed psychological factors and bowel movement frequency (BMF) and duration (BMD) were recorded daily. RESULTS MLD significantly improved all ANS measures (p≤0.01); AM significantly improved LF, HF and LF/HF ratios (p = 0.04); and ES significantly improved LF (p = 0.1). STAI measures improved, but not significantly in all groups. SRI improved significantly from MLD (p < 0.01), AM (p = 0.04) and ES (p < 0.01), but changes were not significant between groups. BMD improved significantly in all groups (p≤ 0.02). BMF improved significantly only following MLD and AM (p < 0.1), but differences between groups were not significant (p = 0.39). CONCLUSIONS MLD significantly reduced FC symptoms and MLD had greater improvements than AM or ES.
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Affiliation(s)
- Jacqueline S. Drouin
- School of Health Sciences, Oakland University, 433 Meadow Brook Road, Rochester, MI 48309-4451, USA;
| | - Lucinda Pfalzer
- Physical Therapy Department, University of Michigan-Flint, 2157 WSW Bldg., Flint, MI 48502-195, USA;
| | - Jung Myo Shim
- Department of Skin and Health Care, Suseong University, 15 Dalgubeol-daero 528-gil, Suseong-gu, Daegu 13557, Korea;
| | - Seong Jung Kim
- Department of Physical Therapy, College of Health and Science, Kangwon National University, 346, Hwangjo-gil, Dogye-eup, Samcheok-si, Gangwon-do 24341, Korea
- Correspondence: ; Tel.: +82-33-540-3371
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34
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Zhong B, Ma S, Wang DH. Ablation of TRPV1 Elevates Nocturnal Blood Pressure in Western Diet-fed Mice. Curr Hypertens Rev 2020; 15:144-153. [PMID: 30381083 PMCID: PMC6635649 DOI: 10.2174/1573402114666181031141840] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2018] [Revised: 09/24/2018] [Accepted: 10/24/2018] [Indexed: 12/28/2022]
Abstract
Background: This study tested the hypothesis that genetically ablation of transient receptor potential vanilloid type 1 (TRPV1) exacerbates impairment of baroreflex in mice fed a western diet (WD) and leads to distinct diurnal and nocturnal blood pressure patterns. Methods: TRPV1 gene knockout (TRPV1-/-) and wild-type (WT) mice were given a WD or normal diet (CON) for 4 months. Results: Capsaicin, a selective TRPV1 agonist, increased ipsilateral afferent renal nerve activity in WT but not TRPV1-/- mice. The sensitivity of renal sympathetic nerve activity and heart rate responses to baroreflex were reduced in TRPV1-/--CON and WT-WD and further decreased in TRPV1-/--WD compared to the WT-CON group. Urinary norepinephrine and serum insulin and leptin at day and night were increased in WT-WD and TRPV1-/--WD, with further elevation at night in TRPV1-/--WD. WD intake increased leptin, IL-6, and TNF-α in adipose tissue, and TNF-α antagonist III, R-7050, decreased leptin in TRPV1-/--WD. The urinary albumin level was higher in TRPV1-/--WD than WT-WD. Blood pressure was not dif-ferent during daytime among all groups, but increased at night in the TRPV1-/--WD group compared with other groups. Conclusions: TRPV1 ablation leads to elevated nocturnal but not diurnal blood pressure, which is probably attributed to fur-ther enhancement of sympathetic drives at night.
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Affiliation(s)
- Beihua Zhong
- Division of Nanomedicine and Molecular Intervention, Department of Medicine, Michigan State University, East Lansing, Michigan MI 48824, United States
| | - Shuangtao Ma
- Division of Nanomedicine and Molecular Intervention, Department of Medicine, Michigan State University, East Lansing, Michigan MI 48824, United States
| | - Donna H Wang
- Division of Nanomedicine and Molecular Intervention, Department of Medicine, Michigan State University, East Lansing, Michigan MI 48824, United States.,Neuroscience Program, Michigan State University, East Lansing, Michigan MI 48824, United States.,Cell & Molecular Biology Program, Michigan State University, East Lansing, Michigan MI 48824, United States
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35
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El Hajj MC, Litwin SE. Echocardiography in the Era of Obesity. J Am Soc Echocardiogr 2020; 33:779-787. [PMID: 32359803 DOI: 10.1016/j.echo.2020.03.009] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/24/2019] [Revised: 03/12/2020] [Accepted: 03/12/2020] [Indexed: 12/29/2022]
Abstract
Patients with obesity are at increased risk for coronary artery disease and heart failure and often present with symptoms of dyspnea, fatigue, edema, or chest pain. Echocardiography is frequently used to help distinguish whether these symptoms are due to cardiac disease. Unfortunately, obesity has a significant impact on image quality because of signal attenuation. Ultrasound-enhancing agents may improve the detection of structural remodeling and subclinical left ventricular dysfunction in patients with obesity. Assessment of chamber sizes and cardiac remodeling in severely obese subjects must be interpreted with caution, however, as the current recommendations for indexing cardiac chamber sizes to body size may lead to false conclusions about chamber volumes or mass, particularly in settings in which weight is changing. As a result of increases in stroke volume and cardiac output, obesity may exacerbate hemodynamic compromise in obstructive structural or valvular disease. With regard to assessment of ischemic heart disease, stress echocardiography can effectively risk-stratify patients with obesity and may have advantages over other noninvasive modalities. In general, transesophageal echocardiography is safe in patients with obesity, although some precautions should be observed. Stress echocardiography using the transesophageal approach is an alternative for preoperative or ischemia evaluation in patients with suboptimal transthoracic views.
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Affiliation(s)
- Milad C El Hajj
- Department of Internal Medicine, Medical University of South Carolina, Charleston, South Carolina
| | - Sheldon E Litwin
- Division of Cardiology, Department of Medicine, Medical University of South Carolina, Charleston, South Carolina; Division of Cardiology, Ralph H. Johnson Veterans Affairs Medical Center, Charleston, South Carolina.
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Kumar M, Maqbool S. Memory improvement by modafinil at cost of metabolic hazards? A study to decipher the benefits and risks of modafinil in rats. Neurotoxicology 2020; 78:106-115. [PMID: 32126242 DOI: 10.1016/j.neuro.2020.02.014] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2019] [Revised: 02/27/2020] [Accepted: 02/28/2020] [Indexed: 11/18/2022]
Abstract
BACKGROUND Modafinil is approved for narcolepsy and achieved high success in off-label indications in memory-related disorders. However, chronic indiscriminate use of modafinil imposes several health hazards like hyperglycaemia, obesity and metabolic syndrome, owing to impairment of sleep-wake cycle, circadian-rhythm, and neurotransmission. The present protocol elucidates the effects of modafinil per se and diabetic complications apropos. METHODS Modafinil (100 and 200 mg/kg) was administered in rats from day 5-26. To induce type-2 diabetes, streptozotocin (STZ) was given on day 1, and blood glucose assessed on day 5. CPP (combination propranolol and phentolamine) was administered to antagonize sympathetic activity. After evaluation of cognitive functions, serum lipid profile, and biomarkers of oxidative stress and acetylcholinesterase (AChE) activity were assessed. RESULTS Subacute dosing of modafinil significantly elevated blood glucose levels, albeit considerably less than diabetic group, and attenuated brain oxidative stress and AChE activity. Modafinil caused significant dyslipidaemia, increased body weight, whereas modestly altered abdominal circumference (AC) and thoracic circumference (TC) in rats. Significant hyperglycaemia, derangement of serum lipid-profile, brain lipid peroxidation, cholinergic hypofunction, and decrease in body weight and ACTC was noted in diabetic rats. Modafinil (100 mg/kg) significantly potentiated the hyperglycaemia and dyslipidaemia, however, attenuated oxidative stress and AChE activity in diabetic rats. Modafinil increased short-term (working) memory but not long-term spatial memory in normal and diabetic rats. CPP infusion attenuated these effects of modafinil. CONCLUSION Subacute dosing of modafinil differentially modulates long-term and short-term memory subtypes, and also predisposes towards metabolic derangements.
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Affiliation(s)
- Manish Kumar
- Department of Pharmacology, Swift School of Pharmacy, Ghaggar Sarai (Rajpura), Punjab, 140401, India.
| | - Shahnawaz Maqbool
- Department of Pharmacology, Swift School of Pharmacy, Ghaggar Sarai (Rajpura), Punjab, 140401, India
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Cohen JR, Thomsen KN, Tu KM, Thakur H, McNeil S, Menon SV. Cardiac autonomic functioning and post-traumatic stress: A preliminary study in youth at-risk for PTSD. Psychiatry Res 2020; 284:112684. [PMID: 31740215 DOI: 10.1016/j.psychres.2019.112684] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2019] [Revised: 11/06/2019] [Accepted: 11/06/2019] [Indexed: 12/14/2022]
Abstract
The identification of robust, psychophysiological markers of trauma-related distress is critical for developing comprehensive, trauma-informed, mental health assessments for youth. Thus, the present study examined the clinical utility of cardiac autonomic balance (CAB) and cardiac autonomic regulation (CAR), two composite indices of the sympathetic and parasympathetic nervous system. We hypothesized that CAB/CAR would more reliably index post-traumatic stress (PTS) responses compared to measuring the parasympathetic (i.e., respiratory sinus arrhythmia; RSA) and sympathetic (i.e., pre-ejection period; PEP) nervous systems in isolation. Our sample was comprised of 88 diverse, low-income youth (40.9% African-American and 36.4% White; 60.5% girls; Mage = 12.05 years; SDage = 1.57) who are at increased risk for adversity-exposure. RSA and PEP were measured during a 5-minute baseline period and 5-minute parent-child conflict discussion task. Adolescent-caregiver dyads completed a clinician-administered measure of the youth's lifetime trauma-exposure and current PTS. CAB represented the difference between RSA and PEP, while CAR was the summation of RSA and PEP. Analyses revealed that sympathetically-oriented CAB reactivity uniquely (a) indexed PTS, especially in the context of elevated trauma, and (b) distinguished between those with and without PTSD. Findings highlight the translational promise of using physiological markers that account for the balance between the parasympathetic and sympathetic nervous system.
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Affiliation(s)
- Joseph R Cohen
- Department of Psychology, University of Illinois Urbana-Champaign, 603 E. Daniel St., Champaign, IL 61820, United States.
| | - Kari N Thomsen
- Department of Psychology, University of Illinois Urbana-Champaign, 603 E. Daniel St., Champaign, IL 61820, United States
| | - Kelly M Tu
- Department of Human Development and Family Services, University of Illinois-Urbana-Champaign, United States
| | - Hena Thakur
- Department of Psychology, University of Illinois Urbana-Champaign, 603 E. Daniel St., Champaign, IL 61820, United States
| | - Shiesha McNeil
- Department of Psychology, University of Illinois Urbana-Champaign, 603 E. Daniel St., Champaign, IL 61820, United States
| | - Suvarna V Menon
- Department of Psychology, University of Illinois Urbana-Champaign, 603 E. Daniel St., Champaign, IL 61820, United States
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Saxton SN, Clark BJ, Withers SB, Eringa EC, Heagerty AM. Mechanistic Links Between Obesity, Diabetes, and Blood Pressure: Role of Perivascular Adipose Tissue. Physiol Rev 2019; 99:1701-1763. [PMID: 31339053 DOI: 10.1152/physrev.00034.2018] [Citation(s) in RCA: 163] [Impact Index Per Article: 27.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
Obesity is increasingly prevalent and is associated with substantial cardiovascular risk. Adipose tissue distribution and morphology play a key role in determining the degree of adverse effects, and a key factor in the disease process appears to be the inflammatory cell population in adipose tissue. Healthy adipose tissue secretes a number of vasoactive adipokines and anti-inflammatory cytokines, and changes to this secretory profile will contribute to pathogenesis in obesity. In this review, we discuss the links between adipokine dysregulation and the development of hypertension and diabetes and explore the potential for manipulating adipose tissue morphology and its immune cell population to improve cardiovascular health in obesity.
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Affiliation(s)
- Sophie N Saxton
- Division of Cardiovascular Sciences, University of Manchester, Manchester, United Kingdom; School of Environment and Life Sciences, University of Salford, Salford, United Kingdom; and Department of Physiology, VU University Medical Centre, Amsterdam, Netherlands
| | - Ben J Clark
- Division of Cardiovascular Sciences, University of Manchester, Manchester, United Kingdom; School of Environment and Life Sciences, University of Salford, Salford, United Kingdom; and Department of Physiology, VU University Medical Centre, Amsterdam, Netherlands
| | - Sarah B Withers
- Division of Cardiovascular Sciences, University of Manchester, Manchester, United Kingdom; School of Environment and Life Sciences, University of Salford, Salford, United Kingdom; and Department of Physiology, VU University Medical Centre, Amsterdam, Netherlands
| | - Etto C Eringa
- Division of Cardiovascular Sciences, University of Manchester, Manchester, United Kingdom; School of Environment and Life Sciences, University of Salford, Salford, United Kingdom; and Department of Physiology, VU University Medical Centre, Amsterdam, Netherlands
| | - Anthony M Heagerty
- Division of Cardiovascular Sciences, University of Manchester, Manchester, United Kingdom; School of Environment and Life Sciences, University of Salford, Salford, United Kingdom; and Department of Physiology, VU University Medical Centre, Amsterdam, Netherlands
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Slušnienė A, Laucevičius A, Navickas P, Ryliškytė L, Stankus V, Stankus A, Navickas R, Laucevičienė I, Kasiulevičius V. Daily Heart Rate Variability Indices in Subjects with and Without Metabolic Syndrome Before and After the Elimination of the Influence of Day-Time Physical Activity. ACTA ACUST UNITED AC 2019; 55:medicina55100700. [PMID: 31627461 PMCID: PMC6843357 DOI: 10.3390/medicina55100700] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2019] [Revised: 10/09/2019] [Accepted: 10/14/2019] [Indexed: 12/30/2022]
Abstract
Background and Objectives: The available research shows conflicting data on the heart rate variability (HRV) in metabolic syndrome (MetS) subjects. The discrepancy suggests a methodical shortcoming: due to the influence of physical activity, the standard measuring of HRV at rest is not comparable with HRV assessment based on 24 h Holter monitoring, which is preferred because of its comprehensiveness. To obtain a more reliable measure and to clarify to what extent HRV is altered in MetS, we assessed a 24 h HRV before and after the elimination of the influence of physical activity. Materials and Methods: We investigated 69 metabolic syndrome (MetS) and 37 control subjects, aged 50–55. In all subjects, 24 h monitoring of electrocardiogram, blood pressure, and actigraphy profiles were conducted. To eliminate the influence of day-time physical activity on RR intervals (RRI), a linear polynomial autoregressive model with exogenous terms (ARX) was used. Standard spectral RRI analysis was performed. Results: Subjects with MetS had blunted HRV; the diurnal SDNN index was reliably lower in the MetS group than in control subjects. The elimination of the influence of physical activity did not reveal a significant HRV change in long-term indices (SDNN, SDANN, and SD2), whilst adjacent RRI values (RMSSD, pNN50, and SD1) and SDNN index significantly increased (p < 0.001). An increase in the latter indices highlighted the HRV difference between the MetS and control groups; a significant (p < 0.001) decrease of all short-term HRV variables was found in the MetS group (p < 0.01), and low-frequency spectral components were less pronounced in the MetS group. Conclusion: The application of a polynomial autoregressive model in 24 h HRV assessment allowed for the exclusion of the influence of physical activity and revealed that MetS is associated with blunted HRV, which reflects mitigated parasympathetic tone.
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Affiliation(s)
- Anžela Slušnienė
- State Research Institute Centre for Innovative Medicine, LT-08406 Vilnius, Lithuania; (A.S.); (A.L.); (A.S.); (R.N.)
- InMedica, LT-08406 Vilnius, Lithuania
| | - Aleksandras Laucevičius
- State Research Institute Centre for Innovative Medicine, LT-08406 Vilnius, Lithuania; (A.S.); (A.L.); (A.S.); (R.N.)
- InMedica, LT-08406 Vilnius, Lithuania
- Faculty of Medicine, Vilnius University, LT-03101 Vilnius, Lithuania; (L.R.); (I.L.); (V.K.)
- Centre of Cardiology and Angiology, Vilnius University Hospital Santaros Klinikos, LT-08661 Vilnius, Lithuania
| | - Petras Navickas
- InMedica, LT-08406 Vilnius, Lithuania
- Faculty of Medicine, Vilnius University, LT-03101 Vilnius, Lithuania; (L.R.); (I.L.); (V.K.)
- Centre of Cardiology and Angiology, Vilnius University Hospital Santaros Klinikos, LT-08661 Vilnius, Lithuania
- Correspondence:
| | - Ligita Ryliškytė
- Faculty of Medicine, Vilnius University, LT-03101 Vilnius, Lithuania; (L.R.); (I.L.); (V.K.)
- Centre of Cardiology and Angiology, Vilnius University Hospital Santaros Klinikos, LT-08661 Vilnius, Lithuania
| | | | - Albinas Stankus
- State Research Institute Centre for Innovative Medicine, LT-08406 Vilnius, Lithuania; (A.S.); (A.L.); (A.S.); (R.N.)
| | - Rokas Navickas
- State Research Institute Centre for Innovative Medicine, LT-08406 Vilnius, Lithuania; (A.S.); (A.L.); (A.S.); (R.N.)
- Faculty of Medicine, Vilnius University, LT-03101 Vilnius, Lithuania; (L.R.); (I.L.); (V.K.)
| | - Ieva Laucevičienė
- Faculty of Medicine, Vilnius University, LT-03101 Vilnius, Lithuania; (L.R.); (I.L.); (V.K.)
- Centre of Rehabilitation, Vilnius University Hospital Santaros Klinikos, Physical and Sports Medicine, LT-08661 Vilnius, Lithuania
| | - Vytautas Kasiulevičius
- Faculty of Medicine, Vilnius University, LT-03101 Vilnius, Lithuania; (L.R.); (I.L.); (V.K.)
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Gorky J, Schwaber J. Conceptualization of a Parasympathetic Endocrine System. Front Neurosci 2019; 13:1008. [PMID: 31607849 PMCID: PMC6767939 DOI: 10.3389/fnins.2019.01008] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2019] [Accepted: 09/05/2019] [Indexed: 12/18/2022] Open
Abstract
We here propose a parasympathetic endocrine system (PES) comprised of circulating peptides released from secretory cells in the gut, significantly modulated by vagal projections from the dorsal motor nucleus of the vagus (DMV). While most of these gut peptides mediate well-described satiety and digestive effects that increase parasympathetic control of digestion (Lee et al., 1994; Gutzwiller et al., 1999; Klok et al., 2007), they also have actions that are far-reaching and increase parasympathetic signaling broadly throughout the body. The actions beyond satiety that peptides like somatostatin, cholecystokinin, glucagon-like peptide 1, and vasoactive intestinal peptide have been well-examined, but not in a systematic way. Consideration has been given to the idea that these and other gut-derived peptides are part of an endocrine system has been partially considered (Rehfeld, 2012; Drucker, 2016), but that it is coordinated through parasympathetic control and may act to increase the actions of parasympathetic projections has not been formalized before. Here only gut-derived hormones are included although there are potentially other parasympathetically mediated factors released from other sites like lung and liver (Drucker, 2016). The case for the existence of the PES with the DMV as its integrative controller will be made through examination of an anatomical substrate and evidence of physiological control mechanisms as well as direct examples of PES antagonism of sympathetic signaling in mammals, including humans. The implications for this conceptual understanding of a PES reframe diseases like metabolic syndrome and may help underscore the role of the autonomic nervous system in the associated symptoms.
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Affiliation(s)
- Jonathan Gorky
- Daniel Baugh Institute for Functional Genomics and Computational Biology, Thomas Jefferson University, Philadelphia, PA, United States
| | - James Schwaber
- Daniel Baugh Institute for Functional Genomics and Computational Biology, Thomas Jefferson University, Philadelphia, PA, United States
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Doom JR, Lumeng JC, Sturza J, Kaciroti N, Vazquez DM, Miller AL. Longitudinal associations between overweight/obesity and stress biology in low-income children. Int J Obes (Lond) 2019; 44:646-655. [PMID: 31477784 PMCID: PMC7050333 DOI: 10.1038/s41366-019-0447-4] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2019] [Revised: 07/01/2019] [Accepted: 07/22/2019] [Indexed: 01/22/2023]
Abstract
Background/Objectives Associations between overweight and altered stress biology have been reported cross-sectionally during childhood, but it is unclear whether overweight precedes altered stress biology or if altered stress biology predicts greater likelihood of overweight over time. The current longitudinal study investigates associations between overweight/obesity, salivary alpha amylase and cortisol morning intercept, diurnal slope, and reactivity to social stress in a cohort of low-income children during preschool and middle childhood. Subjects/Methods Children were recruited through Head Start and were observed and followed into middle childhood (N = 257; M = 8.0 years). Height and weight were measured at both time points. Saliva samples were collected across the day and in response to a social challenge at both ages for alpha amylase and cortisol determination. Results Cross-lagged panel analyses indicated that overweight/obesity at preschool predicted lower morning alpha amylase (β = −0.18, 95% CI: −0.34, −0.03; p = .023), lower morning cortisol (β = −0.22, 95% CI: −0.38, −0.06; p = .006), lower sAA diurnal slope (β = −0.18, 95% CI: −0.34, −0.03; p = .021), and lower cortisol stress reactivity (β = −0.19, 95% CI: −0.35, −0.02; p = .031) in middle childhood. Lower alpha amylase reactivity at preschool was the only biological factor that predicted higher likelihood of overweight/obesity at middle childhood (β = −0.20, 95% CI: −0.38, −0.01; p = .035). Conclusions These findings suggest that overweight/obesity may be driving changes in stress biology across early to middle childhood, particularly in down-regulation of morning levels of stress hormones, diurnal sAA slope, and cortisol reactivity to stress, rather than stress biology driving overweight/obesity.
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Affiliation(s)
- Jenalee R Doom
- Department of Psychology, University of Denver, Denver, CO, USA. .,Department of Pediatrics, University of Michigan Medical School, Ann Arbor, MI, USA. .,Center for Human Growth & Development, University of Michigan, Ann Arbor, MI, USA.
| | - Julie C Lumeng
- Department of Pediatrics, University of Michigan Medical School, Ann Arbor, MI, USA.,Center for Human Growth & Development, University of Michigan, Ann Arbor, MI, USA.,Department of Nutritional Sciences, University of Michigan School of Public Health, Ann Arbor, MI, USA
| | - Julie Sturza
- Department of Pediatrics, University of Michigan Medical School, Ann Arbor, MI, USA.,Center for Human Growth & Development, University of Michigan, Ann Arbor, MI, USA
| | - Niko Kaciroti
- Center for Human Growth & Development, University of Michigan, Ann Arbor, MI, USA.,Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, USA
| | - Delia M Vazquez
- Department of Pediatrics, University of Michigan Medical School, Ann Arbor, MI, USA.,Center for Human Growth & Development, University of Michigan, Ann Arbor, MI, USA
| | - Alison L Miller
- Center for Human Growth & Development, University of Michigan, Ann Arbor, MI, USA.,Department of Health Behavior and Health Education, University of Michigan School of Public Health, Ann Arbor, MI, USA
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Frequency of Polymorphic Options G894T Genotype of Endothelial NO-synthase in Patients with Arterial Hypertension and Surface Mass of the Type. Fam Med 2019. [DOI: 10.30841/2307-5112.3.2019.178586] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
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Abstract
Perivascular adipose tissue (PVAT) is no longer recognised as simply a structural support for the vasculature, and we now know that PVAT releases vasoactive factors which modulate vascular function. Since the discovery of this function in 1991, PVAT research is rapidly growing and the importance of PVAT function in disease is becoming increasingly clear. Obesity is associated with a plethora of vascular conditions; therefore, the study of adipocytes and their effects on the vasculature is vital. PVAT contains an adrenergic system including nerves, adrenoceptors and transporters. In obesity, the autonomic nervous system is dysfunctional; therefore, sympathetic innervation of PVAT may be the key mechanistic link between increased adiposity and vascular disease. In addition, not all obese people develop vascular disease, but a common feature amongst those that do appears to be the inflammatory cell population in PVAT. This review will discuss what is known about sympathetic innervation of PVAT, and the links between nerve activation and inflammation in obesity. In addition, we will examine the therapeutic potential of exercise in sympathetic stimulation of adipose tissue.
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Affiliation(s)
- Sophie N Saxton
- Division of Cardiovascular Sciences, Manchester Academic Health Science Centre, University of Manchester, Core Technology Facility (3rd floor), 46 Grafton Street, M13 9NT, Manchester, UK.
| | - Sarah B Withers
- Division of Cardiovascular Sciences, Manchester Academic Health Science Centre, University of Manchester, Core Technology Facility (3rd floor), 46 Grafton Street, M13 9NT, Manchester, UK
- School of Environment and Life Sciences, University of Salford, Manchester, UK
| | - Anthony M Heagerty
- Division of Cardiovascular Sciences, Manchester Academic Health Science Centre, University of Manchester, Core Technology Facility (3rd floor), 46 Grafton Street, M13 9NT, Manchester, UK
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Tófolo LP, Rinaldi W, Gôngora AB, Matiusso CCI, Pavanello A, Malta A, de Almeida DL, Ribeiro TA, Oliveira AR, Peres MNC, Armitage JA, Mathias PCDF, Palma-Rigo K. Moderate Physical Training Ameliorates Cardiovascular Dysfunction Induced by High Fat Diet After Cessation of Training in Adult Rats. Front Physiol 2019; 10:170. [PMID: 30930783 PMCID: PMC6423496 DOI: 10.3389/fphys.2019.00170] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2018] [Accepted: 02/12/2019] [Indexed: 12/11/2022] Open
Abstract
We aimed to test whether moderate physical training can induce long-lasting protection against cardiovascular risk factors induced by high fat diet (HFD) intake, even after cessation of training. 90-days-old Wistar rats were submitted to a sedentary lifestyle or moderate physical training, three times a week, for 30 days. Following this, at 120 days-of age, sedentary and trained rats received a hypercaloric diet (HFD) or a commercial diet normal fat diet (NFD) for 30 days. Body weight (BW) and food intake were evaluated weekly. At 150 days-of age, hemodynamic measures (systolic, diastolic, mean blood pressure, pulse pressure, pulse interval and heart rate) were made via an indwelling femoral artery catheter. Beat-to-beat data were analyzed to calculate power spectra of systolic blood pressure (SBP) and pulse interval. After euthanasia, mesenteric fat pads were removed and weighted and total blood was stored for later analysis of lipid profile. Consumption of a HFD increased blood pressure (BP), pulse pressure, low frequency BP variability, BW gain, fat pad stores and induced dyslipidemia. Interestingly, prior physical training was able to partially protect against this rise in BP and body fat stores. Prior physical training did not totally protect against the effects of HFD consumption but previously trained animals did demonstrate resistance to the development of cardiometabolic alterations, which illustrate that the benefits of physical training may be partially maintained even after 30 days of detraining period.
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Affiliation(s)
- Laize Peron Tófolo
- Laboratory of Secretion Cell Biology, Department of Biotechnology, Genetics and Cell Biology, State University of Maringá, Maringá, Brazil.,Department of Physical Education, Faculty of Biomedical Sciences of Cacoal, Cacoal, Brazil
| | - Wilson Rinaldi
- Department of Physical Education, State University of Maringá, Maringá, Brazil
| | - Adriane Barreto Gôngora
- Laboratory of Secretion Cell Biology, Department of Biotechnology, Genetics and Cell Biology, State University of Maringá, Maringá, Brazil
| | - Camila Cristina Ianoni Matiusso
- Laboratory of Secretion Cell Biology, Department of Biotechnology, Genetics and Cell Biology, State University of Maringá, Maringá, Brazil
| | - Audrei Pavanello
- Laboratory of Secretion Cell Biology, Department of Biotechnology, Genetics and Cell Biology, State University of Maringá, Maringá, Brazil
| | - Ananda Malta
- Laboratory of Secretion Cell Biology, Department of Biotechnology, Genetics and Cell Biology, State University of Maringá, Maringá, Brazil
| | - Douglas Lopes de Almeida
- Laboratory of Secretion Cell Biology, Department of Biotechnology, Genetics and Cell Biology, State University of Maringá, Maringá, Brazil
| | - Tatiane Aparecida Ribeiro
- Laboratory of Secretion Cell Biology, Department of Biotechnology, Genetics and Cell Biology, State University of Maringá, Maringá, Brazil
| | | | - Maria Natalia Chimirri Peres
- Laboratory of Secretion Cell Biology, Department of Biotechnology, Genetics and Cell Biology, State University of Maringá, Maringá, Brazil
| | | | - Paulo Cezar de Freitas Mathias
- Laboratory of Secretion Cell Biology, Department of Biotechnology, Genetics and Cell Biology, State University of Maringá, Maringá, Brazil
| | - Kesia Palma-Rigo
- Laboratory of Secretion Cell Biology, Department of Biotechnology, Genetics and Cell Biology, State University of Maringá, Maringá, Brazil.,Faculdade Adventista Paranaense, Ivatuba, Brazil
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Mai K, Li L, Wiegand S, Brachs M, Leupelt V, Ernert A, Kühnen P, Hübner N, Robinson P, Chen W, Krude H, Spranger J. An Integrated Understanding of the Molecular Mechanisms of How Adipose Tissue Metabolism Affects Long-term Body Weight Maintenance. Diabetes 2019; 68:57-65. [PMID: 30389745 DOI: 10.2337/db18-0440] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2018] [Accepted: 10/22/2018] [Indexed: 11/13/2022]
Abstract
Lifestyle-based weight loss interventions frequently demonstrate long-term inefficiency and weight regain. Identification of underlying mechanisms and predictors to identify subjects who will benefit from lifestyle-based weight loss strategies is urgently required. We analyzed 143 adults of the randomized Maintain trial (Maintain-Adults) after intended weight loss to identify mechanisms contributing to the regulation of body weight maintenance. Unbiased RNA sequencing of adipose and skeletal muscle biopsies revealed fatty acid metabolism as a key pathway modified by weight loss. Variability of key enzymes of this pathway, estimates of substrate oxidation, and specific serum acylcarnitine (AC) species, representing a systemic snapshot of in vivo substrate flux, predicted body weight maintenance (defined as continuous or dichotomized [< or ≥3% weight regain] variable) 18 months after intended weight loss in the entire cohort. Key results were confirmed in a similar randomized controlled trial in 137 children and adolescents (Maintain-Children), which investigated the same paradigm in a pediatric cohort. These data suggest that adaption of lipid utilization in response to negative energy balance contributes to subsequent weight maintenance. Particularly a functional role for circulating ACs, which have been suggested to reflect intracellular substrate utilization, as mediators between peripheral energy stores and control of long-term energy homeostasis was indicated.
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Affiliation(s)
- Knut Mai
- Department of Endocrinology and Metabolism, Charité-Universitätsmedizin Berlin, Berlin, Germany
- Charité-Center for Cardiovascular Research, Berlin, Germany
- Clinical Research Unit, Berlin Institute of Health, Berlin, Germany
- German Centre for Cardiovascular Research (DZHK), Partner Site Berlin, Berlin, Germany
| | - Linna Li
- Department of Endocrinology and Metabolism, Charité-Universitätsmedizin Berlin, Berlin, Germany
- Clinical Research Unit, Berlin Institute of Health, Berlin, Germany
- German Centre for Cardiovascular Research (DZHK), Partner Site Berlin, Berlin, Germany
| | - Susanna Wiegand
- Department of Pediatric Endocrinology and Diabetology, Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Maria Brachs
- Department of Endocrinology and Metabolism, Charité-Universitätsmedizin Berlin, Berlin, Germany
- Charité-Center for Cardiovascular Research, Berlin, Germany
| | - Verena Leupelt
- Department of Endocrinology and Metabolism, Charité-Universitätsmedizin Berlin, Berlin, Germany
- Charité-Center for Cardiovascular Research, Berlin, Germany
| | - Andrea Ernert
- Department of Pediatric Endocrinology and Diabetology, Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Peter Kühnen
- Department of Pediatric Endocrinology and Diabetology, Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Norbert Hübner
- German Centre for Cardiovascular Research (DZHK), Partner Site Berlin, Berlin, Germany
- Max Delbrück Center for Molecular Medicine, Berlin, Germany
| | - Peter Robinson
- Institute for Medical Genetics, Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Wei Chen
- Max Delbrück Center for Molecular Medicine, Berlin, Germany
| | - Heiko Krude
- Department of Pediatric Endocrinology and Diabetology, Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Joachim Spranger
- Department of Endocrinology and Metabolism, Charité-Universitätsmedizin Berlin, Berlin, Germany
- Charité-Center for Cardiovascular Research, Berlin, Germany
- Clinical Research Unit, Berlin Institute of Health, Berlin, Germany
- German Centre for Cardiovascular Research (DZHK), Partner Site Berlin, Berlin, Germany
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Berntson GG. Presidential Address 2011: Autonomic modes of control and health. Psychophysiology 2019; 56:e13306. [PMID: 30556212 DOI: 10.1111/psyp.13306] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2018] [Revised: 10/30/2018] [Accepted: 10/30/2018] [Indexed: 12/19/2022]
Abstract
Understanding psychosomatic relations, and their implications for heath, is importantly dependent on our conceptual and measurement models. The historical view of reciprocal control of the autonomic branches is applicable in some contexts, but not others. Control of the autonomic branches can vary reciprocally, independently, and even coactively. Assessment of sympathovagal balance, based on a reciprocal model of regulation of the autonomic branches, may have applications in orthostatic contexts and in insulin resistance in diabetes. However, it does not adequately capture the pattern of autonomic control that is relevant for myocardial infarction (MI; in humans) and experimental cardiac arrest (in mice). A measure of sympathovagal balance (cardiac autonomic balance) was predictive and informative of the autonomic contributions to diabetes but was blind to autonomic contributions to cardiac arrest and its sequelae. However, a metric designed to capture the coactivity dimension of cardiac autonomic regulation (CAR) was predictive of MI and its sequelae. Both human and animal model studies revealed that low CAR (low sympathetic and especially low parasympathetic control) predicted the occurrence of MI and the neuroinflammatory consequences of cardiac arrest. These effects were importantly modulated by social support in both humans and animals, via an apparent oxytocinergic pathway that impacts parasympathetic cardiac control and CAR, and thus neuroinflammation. Results indicate the importance of a physiologically meaningful model of autonomic control in understanding health implications of the modes of autonomic control.
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Affiliation(s)
- Gary G Berntson
- Department of Psychology, The Ohio State University, Columbus, Ohio
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Valdez JM, Johnstone AFM, Richards JE, Schmid JE, Royland JE, Kodavanti PRS. Interaction of Diet and Ozone Exposure on Oxidative Stress Parameters within Specific Brain Regions of Male Brown Norway Rats. Int J Mol Sci 2018; 20:ijms20010011. [PMID: 30577502 PMCID: PMC6337237 DOI: 10.3390/ijms20010011] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2018] [Revised: 11/29/2018] [Accepted: 12/18/2018] [Indexed: 12/18/2022] Open
Abstract
Oxidative stress (OS) contributes to the neurological and cardio/pulmonary effects caused by adverse metabolic states and air pollutants such as ozone (O3). This study explores the interactive effects of O3 and diet (high-fructose (FRUC) or high–fat (FAT)) on OS in different rat brain regions. In acute exposure, there was a decrease in markers of reactive oxygen species (ROS) production in some brain regions by diet and not by O3. Total antioxidant substances (TAS) were increased in the cerebellum (CER) and frontal cortex (FC) and decreased in the striatum (STR) by both diets irrespective of O3 exposure. Protein carbonyls (PC) and total aconitase decreased in some brain regions irrespective of exposure. Following subacute exposure, an increase in markers of ROS was observed in both diet groups. TAS was increased in the FC (FAT only) and there was a clear O3 effect where TAS was increased in the FC and STR. Diet increased PC formation within the CER in the FAT group, while the hippocampus showed a decrease in PC after O3 exposure in controls. In general, these results indicate that diet/O3 did not have a global effect on brain OS parameters, but showed some brain region- and OS parameter-specific effects by diets.
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Affiliation(s)
- Joseph M Valdez
- Neurotoxicology Branch, Toxicity Assessment Division, NHEERL/ORD, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
| | - Andrew F M Johnstone
- Neurotoxicology Branch, Toxicity Assessment Division, NHEERL/ORD, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
| | - Judy E Richards
- Environmental Public Health Division, NHEERL/ORD, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
| | - Judith E Schmid
- Neurotoxicology Branch, Toxicity Assessment Division, NHEERL/ORD, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
| | - Joyce E Royland
- Integrated Systems Toxicology Division, NHEERL/ORD, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
| | - Prasada Rao S Kodavanti
- Neurotoxicology Branch, Toxicity Assessment Division, NHEERL/ORD, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
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Alpert MA, Karthikeyan K, Abdullah O, Ghadban R. Obesity and Cardiac Remodeling in Adults: Mechanisms and Clinical Implications. Prog Cardiovasc Dis 2018; 61:114-123. [PMID: 29990533 DOI: 10.1016/j.pcad.2018.07.012] [Citation(s) in RCA: 124] [Impact Index Per Article: 17.7] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2018] [Accepted: 07/05/2018] [Indexed: 01/20/2023]
Affiliation(s)
- Martin A Alpert
- Division of Cardiovascular Medicine, University of Missouri School of Medicine, Columbia, MO, USA.
| | - Kamalesh Karthikeyan
- Division of Cardiovascular Medicine, University of Missouri School of Medicine, Columbia, MO, USA
| | - Obai Abdullah
- Division of Cardiovascular Medicine, University of Missouri School of Medicine, Columbia, MO, USA
| | - Rugheed Ghadban
- Division of Cardiovascular Medicine, University of Missouri School of Medicine, Columbia, MO, USA
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Mai K, Brachs M, Leupelt V, Jumpertz-von Schwartzenberg R, Maurer L, Grüters-Kieslich A, Ernert A, Bobbert T, Krude H, Spranger J. Effects of a combined dietary, exercise and behavioral intervention and sympathetic system on body weight maintenance after intended weight loss: Results of a randomized controlled trial. Metabolism 2018; 83:60-67. [PMID: 29360493 DOI: 10.1016/j.metabol.2018.01.003] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2017] [Revised: 12/21/2017] [Accepted: 01/11/2018] [Indexed: 12/22/2022]
Abstract
BACKGROUND Lifestyle based weight loss interventions are hampered by long-term inefficacy. Prediction of individuals successfully reducing body weight would be highly desirable. Although sympathetic activity is known to contribute to energy homeostasis, its predictive role in body weight maintenance has not yet been addressed. OBJECTIVES We investigated, whether weight regain could be modified by a weight maintenance intervention and analyzed the predictive role of weight loss-induced changes of the sympathetic system on long-term weight regain. DESIGN 156 subjects (age > 18; BMI ≥ 27 kg/m2) participated in a 12-week weight reduction program. After weight loss (T0), 143 subjects (weight loss > 8%) were randomized to a 12-month lifestyle intervention or a control group. After 12 months (T12) no further intervention was performed until month 18 (T18). Weight regain at T18 (regainBMI) was the primary outcome. Evaluation of systemic and tissue specific estimates of sympathetic system was a pre-defined secondary outcome. RESULTS BMI was reduced by 4.67 ± 1.47 kg/m2 during the initial weight loss period. BMI maintained low in subjects of the intervention group until T12 (+0.07 ± 2.98 kg/m2; p = 0.58 compared to T0), while control subjects regained +0.98 ± 1.93 kg/m2 (p < 0.001 compared to T0). The intervention group regained more weight than controls after ceasing the intervention (1.17 ± 1.34 vs. 0.57 ± 0.93 kg/m2) until T18. Consequently, BMI was not different at T18 (33.49 (32.64; 34.33) vs. 34.18 (33.61; 34.75) kg/m2; p=0.17). Weight loss-induced modification of urinary metanephrine excretion independently predicted regainBMI (R2 = 0.138; p < 0.05). The lifestyle intervention did not modify the course of urinary metanephrines after initial weight loss. CONCLUSIONS Our lifestyle intervention successfully maintained body weight during the intervention period. However, no long-term effect could be observed beyond the intervention period. Predictive sympathetic activity was not persistently modified by the intervention, which may partially explain the lack of long-term success of such interventions.
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Affiliation(s)
- Knut Mai
- Department of Endocrinology & Metabolism, Charite - Universitätsmedizin Berlin, Germany; Charité-Center for Cardiovascular Research (CCR), Berlin, Germany; Clinical Research Unit, Berlin Institute of Health (BIH); DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Germany.
| | - Maria Brachs
- Department of Endocrinology & Metabolism, Charite - Universitätsmedizin Berlin, Germany; Charité-Center for Cardiovascular Research (CCR), Berlin, Germany; Clinical Research Unit, Berlin Institute of Health (BIH); DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Germany
| | - Verena Leupelt
- Department of Endocrinology & Metabolism, Charite - Universitätsmedizin Berlin, Germany; Charité-Center for Cardiovascular Research (CCR), Berlin, Germany
| | - Reiner Jumpertz-von Schwartzenberg
- Department of Endocrinology & Metabolism, Charite - Universitätsmedizin Berlin, Germany; Charité-Center for Cardiovascular Research (CCR), Berlin, Germany; Clinical Research Unit, Berlin Institute of Health (BIH); DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Germany
| | - Lukas Maurer
- Department of Endocrinology & Metabolism, Charite - Universitätsmedizin Berlin, Germany; Charité-Center for Cardiovascular Research (CCR), Berlin, Germany; Clinical Research Unit, Berlin Institute of Health (BIH); DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Germany
| | - Annette Grüters-Kieslich
- Department of Pediatric Endocrinology and Diabetology, Charité Universitätsmedizin Berlin, Germany
| | - Andrea Ernert
- Department of Pediatric Endocrinology and Diabetology, Charité Universitätsmedizin Berlin, Germany
| | - Thomas Bobbert
- Department of Endocrinology & Metabolism, Charite - Universitätsmedizin Berlin, Germany; Charité-Center for Cardiovascular Research (CCR), Berlin, Germany
| | - Heiko Krude
- Department of Pediatric Endocrinology and Diabetology, Charité Universitätsmedizin Berlin, Germany
| | - Joachim Spranger
- Department of Endocrinology & Metabolism, Charite - Universitätsmedizin Berlin, Germany; Charité-Center for Cardiovascular Research (CCR), Berlin, Germany; Clinical Research Unit, Berlin Institute of Health (BIH); DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Germany
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50
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Endothelial dysfunction in the pathogenesis of arterial hypertension and the progression of atherosclerosis. Fam Med 2018. [DOI: 10.30841/2307-5112.2.2018.145561] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
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