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Yi Y, Qin S, Ding S, Fang J. Polysaccharides in the medicine and food homology to combat obesity via gut-liver axis: A review of possible mechanisms. Int J Biol Macromol 2025; 312:144044. [PMID: 40345304 DOI: 10.1016/j.ijbiomac.2025.144044] [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: 01/15/2025] [Revised: 04/13/2025] [Accepted: 05/06/2025] [Indexed: 05/11/2025]
Abstract
Polysaccharides, as macromolecular carbohydrates present in various medicine and food homology, have gained growing recognition for their potential in combating obesity through multiple mechanisms. Their natural origin and favorable safety profile have made polysaccharides from medicine and food homology (PMFH) an area of significant research interest, particularly in the context of developing effective, safe, and sustainable interventions for obesity management. This review summarized the classification and biological properties of PMFH and then elucidated the pathological characteristics of obesity. We primarily focused on the effects of PMFHs on obesity, with particular attention to the potential mechanisms mediated through the gut-liver axis. These mechanisms encompassed the improvement of fat metabolism imbalances, manager of appetite and energy balance, adjustment of intestinal microbial imbalances, and alleviation of oxidative stress and inflammation. The findings provided critical theoretical insights and data to support the development of anti-obesity dietary and pharmaceutical products. In brief, this review outlined future research directions regarding the potential mechanisms underlying the anti-obesity effects of PMFH, particularly those involving the gut-liver axis.
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Affiliation(s)
- Yuhang Yi
- College of Bioscience and Biotechnology, Hunan Agricultural University, Hunan Engineering Laboratory for Pollution Control and Waste Utilization in Swine Production, Changsha, Hunan 410128, China
| | - Si Qin
- Laboratory of Food Function and Nutrigenomics, College of Food Science and Technology, Hunan Agricultural University, Changsha 410128, China
| | - Sujuan Ding
- College of Bioscience and Biotechnology, Hunan Agricultural University, Hunan Engineering Laboratory for Pollution Control and Waste Utilization in Swine Production, Changsha, Hunan 410128, China.
| | - Jun Fang
- College of Bioscience and Biotechnology, Hunan Agricultural University, Hunan Engineering Laboratory for Pollution Control and Waste Utilization in Swine Production, Changsha, Hunan 410128, China.
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2
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Li J, Ma LJ, Ma XY, Gao B. Relationship between weight-to-waist index and post-stroke depression. World J Psychiatry 2025; 15:100909. [PMID: 40110002 PMCID: PMC11886329 DOI: 10.5498/wjp.v15.i3.100909] [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: 08/30/2024] [Revised: 12/12/2024] [Accepted: 01/20/2025] [Indexed: 02/26/2025] Open
Abstract
BACKGROUND The weight-to-waist index (WWI) serves as an innovative metric specifically designed to assess central obesity. However, the relationship between WWI and the prevalence of post-stroke depression (PSD) remains inadequately explored in the literature. AIM To elucidate the relationship between WWI and PSD. METHODS Data from the National Health and Nutrition Examination Survey 2005 to 2018 were analyzed. Multivariable logistic regression models and propensity score matching were utilized to investigate the association between WWI and PSD, with adjustments for potential confounders. The restricted cubic spline statistical method was applied to explore non-linear associations. RESULTS Participants with elevated WWI values had a significantly greater risk of developing PSD. Specifically, individuals in the higher WWI range exhibited more than twice the likelihood of developing PSD compared to those with lower WWI values (odds ratio = 2.21, 95% confidence interval: 1.84-2.66, P < 0.0001). After propensity score matching, the risk of PSD remained significantly elevated (odds ratio = 1.43, 95%confidence interval: 1.09-1.88, P = 0.01). Tertile analysis revealed that participants in the highest WWI tertile faced a significantly higher risk of PSD compared to those in the lowest tertile. Restricted cubic spline analysis further revealed a non-linear association, with the risk of PSD plateauing at higher WWI values. CONCLUSION There is a significant association between elevated WWI and increased risk of PSD. Thus, regular depression screening should be implemented in stroke patients with elevated WWI to enhance patient outcomes.
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Affiliation(s)
- Juan Li
- Department of Neurology, Xingyuan Hospital of Yulin/4th Hospital of Yulin, Yulin 719000, Shaanxi Province, China
| | - Li-Jun Ma
- Department of Clinical Laboratory, The Affiliated Hospital of Yan’an University, Yan’an 716000, Shaanxi Province, China
| | - Xiao-Yuan Ma
- Department of Operating Theater, The Affiliated Hospital of Yan’an University, Yan’an 716000, Shaanxi Province, China
| | - Bo Gao
- Department of Neurology, The Affiliated Hospital of Yan’an University, Yan’an 716000, Shaanxi Province, China
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3
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An J, Fu D, Chen X, Guan C, Li L, Bai J, Lv H. Revisiting the role of IL-27 in obesity-related metabolic diseases: safeguard or perturbation? Front Immunol 2025; 15:1498288. [PMID: 39906735 PMCID: PMC11792170 DOI: 10.3389/fimmu.2024.1498288] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2024] [Accepted: 12/31/2024] [Indexed: 02/06/2025] Open
Abstract
The prevalence of metabolic diseases, such as obesity, has been steadily increasing in recent years, posing a significant threat to public health. Therefore, early identification and intervention play a crucial role. With the deepening understanding of the etiology of metabolic diseases, novel therapeutic targets are emerging for the treatment of obesity, lipid metabolism disorders, cardiovascular and cerebrovascular diseases, glucose metabolism disorders, and other related metabolic conditions. IL-27, as a multi-potent cytokine, holds great promise as a potential candidate target in this regard. This article provides a comprehensive review of the latest findings on IL-27 expression and signal transduction in the regulation of immune inflammatory cells, as well as its implications in obesity and other related metabolic diseases. Furthermore, it explores the potential of IL-27 as a novel therapeutic target for the treatment of obesity and metabolic disorders. Finally, an overview is presented on both the opportunities and challenges associated with targeting IL-27 for therapeutic interventions.
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Affiliation(s)
- Jinyang An
- The First Clinical Medical College of Lanzhou University, Lanzhou, Gansu, China
| | - Donghua Fu
- Department of Endocrinology, The People’s Hospital of Yuzhong County, Lanzhou, Gansu, China
| | - Ximei Chen
- Department of General Medicine, Zhengzhou Yihe Hospital affiliated to Henan University, Zhengzhou, Henan, China
| | - Conghui Guan
- The First Clinical Medical College of Lanzhou University, Lanzhou, Gansu, China
- Department of Endocrinology, The First Hospital of Lanzhou University, Lanzhou, Gansu, China
| | - Lingling Li
- The First Clinical Medical College of Lanzhou University, Lanzhou, Gansu, China
| | - Jia Bai
- The First Clinical Medical College of Lanzhou University, Lanzhou, Gansu, China
| | - Haihong Lv
- The First Clinical Medical College of Lanzhou University, Lanzhou, Gansu, China
- Department of Endocrinology, The First Hospital of Lanzhou University, Lanzhou, Gansu, China
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Liao Y, Zhou K, Lin B, Deng S, Weng B, Pan L. Associations between systemic immune-inflammatory index and visceral adipose tissue area: results of a national survey. Front Nutr 2025; 11:1517186. [PMID: 39885869 PMCID: PMC11780491 DOI: 10.3389/fnut.2024.1517186] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2024] [Accepted: 12/30/2024] [Indexed: 02/01/2025] Open
Abstract
Background Global health issues related to obesity are growing. Visceral adipose tissue (VAT) significantly contributes to complications associated with obesity. Reducing adipose tissue accumulation can improves inflammation. However, it is still unknown how the systemic immune-inflammation index (SII) and VAT area are related. Methods With the help of multivariate linear regression and smooth curve fitting, the relationship between SII and VAT area was explored with data from the 2013 and 2014 National Health and Nutrition Examination Survey (NHANES). Analyzing subgroups and testing for interaction were used to investigate whether the relationship was accurate across demographics. Results From 20 to 59 years of age, 3,290 individuals were observed to have a positive correlation between SII and VAT area. In accordance with the fully adjusted model, the VAT area increased by 9.34 cm2 for every unit increase in log SII [β = 9.34, 95% CI (4.02, 14.67)]. In the highest quartile of SII, the VAT area was 5.46 cm2 [β = 5.46, 95% CI (2.21, 8.71)] higher than that in the lowest quartile. Additionally, the population that was overweight or obese showed a stronger positive correlation. Conclusion SII has a positive correlation with VAT area in US adults. SII may be valuable in clinical applications to evaluate the severity of VAT area.
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Affiliation(s)
| | | | | | | | | | - Liya Pan
- Department of Neurology, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, China
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5
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Diao B, Fan Z, Zhou B, Zhan H. Crosstalk between pancreatic cancer and adipose tissue: Molecular mechanisms and therapeutic implications. Biochem Biophys Res Commun 2024; 740:151012. [PMID: 39561650 DOI: 10.1016/j.bbrc.2024.151012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2024] [Revised: 11/02/2024] [Accepted: 11/14/2024] [Indexed: 11/21/2024]
Abstract
The incidence rate of pancreatic cancer, a fatal illness with a meager 5-year survival rate, has been on the rise in recent times. When individuals accumulate excessive amounts of adipose tissue, the adipose organ becomes dysfunctional due to alterations in the adipose tissue microenvironment associated with inflammation and metabolism. This phenomenon may potentially contribute to the aberrant accumulation of fat that initiates pancreatic carcinogenesis, thereby influencing the disease's progression, resistance to treatment, and metastasis. This review presents a summary of the impact of pancreatic steatosis, visceral fat, cancer-associated adipocytes and lipid diets on the advancement of pancreatic cancer, as well as the reciprocal effects of pancreatic cancer on adipose tissue. Understanding the molecular mechanisms underlying the relationship between dysfunctional adipose tissue and pancreatic cancer better may lead to the discovery of new therapeutic targets for the disease's prevention and individualized treatment. This is especially important given the rising global incidence of obesity, which will improve the pancreatic cancer treatment options that are currently insufficient.
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Affiliation(s)
- Boyu Diao
- Division of Pancreatic Surgery, Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong Province, China
| | - Zhiyao Fan
- Division of Pancreatic Surgery, Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong Province, China
| | - Bin Zhou
- Department of Hepatobiliary and Pancreatic Surgery, Department of Retroperitoneal Tumor Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, China
| | - Hanxiang Zhan
- Division of Pancreatic Surgery, Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong Province, China.
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Ormindean CM, Ciortea R, Bucuri CE, Măluțan AM, Iuhas CI, Porumb CG, Nicula RL, Ormindean V, Roman MP, Nati ID, Suciu V, Florea A, Solomon C, Moldovan M, Mihu D. Somatic Changes of Maternal High-Fat Diet on Offspring-Possible Deleterious Effects of Flavonoids? Nutrients 2024; 16:4022. [PMID: 39683415 DOI: 10.3390/nu16234022] [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: 10/17/2024] [Revised: 11/17/2024] [Accepted: 11/21/2024] [Indexed: 12/18/2024] Open
Abstract
Background/Objectives: The rapidly increasing rate of obesity has become an extremely important public health problem, particularly in developed countries. Obesity is associated with a range of health problems, often referred to as the metabolic syndrome. Adipose tissue is now regarded as an endocrine organ responsible for the hormonal secretion of adipokines, which are cytokines involved in various physiological processes. It has been established that adipokines play a key role in the regulation of many processes in the human body. The aim of the current study was to use an animal model to investigate the possible influence of obesity and adipokines on the gestational period, on the development of offspring, and to assess whether these changes are influenced by the administration of antioxidant agents and flavonoids. Methods: The present study was performed using 5 groups of 7 female Wistar albino rats. A control group was used to which a 5% lipid diet was administered, and the other 4 groups were fed an obesogenic 65% lipid diet. From the 4 groups that received obesogenic diet one group received no supplement, and the rest of 3 received Detralex, Sel-E-Vit and Rutin (antioxidants and flavonoids). Study times for both pregnant groups and offsprings: on day 15 of gestation, venous blood was drawn to determine adipokine (leptin and visfatin) levels; on days 18-22 ultrasound examination was performed to measure the thickness of adipose tissue in the abdominal wall; for each batch a number of 10 offspring were selected for the measurements (pup weight, brain weight, head length, head width, spine length, width between shoulder blades, coxal bone length), adipokine levels in the offspring (from brain tissue) were also determined, as well as the existence of changes in the brain tissue of the offspring identified by electron microscopy. Results: The results of the study showed that the high-fat diet (HFD) led to a significant increase in body weight and abdominal wall thickness in pregnant females compared to the control group. The levels of leptin and visfatin were also affected by the HFD, with leptin levels being significantly higher in the HFD group and visfatin levels being lower. In the offspring, the HFD group had a significantly higher body mass and brain weight compared to the control group. The anthropometric measurements of the offspring were also affected by the maternal diet, with the HFD group having larger dimensions overall. Interestingly, the offspring of the groups that received flavonoids in addition to the HFD had significantly smaller dimensions compared to both the HFD group and the control group. Conclusions: The results of this experimental study reinforce what is already known about the effects of obesity on the gestation period and offspring and at the same time, the current study highlights the existence of possible adverse effects of flavonoid compounds on the development of pregnancy and offspring, opening the way for future studies on the benefits and risks of using these compounds during gestational period.
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Affiliation(s)
- Cristina Mihaela Ormindean
- 2nd Department of Obstetrics and Gynecology, "Iuliu Haţieganu" University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania
| | - Razvan Ciortea
- 2nd Department of Obstetrics and Gynecology, "Iuliu Haţieganu" University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania
| | - Carmen Elena Bucuri
- 2nd Department of Obstetrics and Gynecology, "Iuliu Haţieganu" University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania
| | - Andrei Mihai Măluțan
- 2nd Department of Obstetrics and Gynecology, "Iuliu Haţieganu" University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania
| | - Cristian Ioan Iuhas
- 2nd Department of Obstetrics and Gynecology, "Iuliu Haţieganu" University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania
| | - Ciprian Gheorghe Porumb
- 2nd Department of Obstetrics and Gynecology, "Iuliu Haţieganu" University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania
| | - Renata Lacramioara Nicula
- 2nd Department of Obstetrics and Gynecology, "Iuliu Haţieganu" University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania
| | - Vlad Ormindean
- 2nd Department of Obstetrics and Gynecology, "Iuliu Haţieganu" University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania
| | - Maria Patricia Roman
- 2nd Department of Obstetrics and Gynecology, "Iuliu Haţieganu" University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania
| | - Ionel Daniel Nati
- 2nd Department of Obstetrics and Gynecology, "Iuliu Haţieganu" University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania
| | - Viorela Suciu
- 2nd Department of Obstetrics and Gynecology, "Iuliu Haţieganu" University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania
| | - Adrian Florea
- Department of Cell and Molecular Biology, Faculty of Medicine, "Iuliu Haţieganu" University of Medicine and Pharmacy, 400349 Cluj-Napoca, Romania
| | - Carolina Solomon
- Radiology Department, "Iuliu Hațieganu" University of Medicine and Pharmacy, 400347 Cluj-Napoca, Romania
| | - Madalina Moldovan
- Department of Physiology, "Iuliu Haţieganu" University of Medicine and Pharmacy, Clinicilor Street, No. 1, 400006 Cluj-Napoca, Romania
| | - Dan Mihu
- 2nd Department of Obstetrics and Gynecology, "Iuliu Haţieganu" University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania
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Tian Y, Huang Q, Ren YT, Jiang X, Jiang B. Visceral adipose tissue predicts severity and prognosis of acute pancreatitis in obese patients. Hepatobiliary Pancreat Dis Int 2024; 23:458-462. [PMID: 37648552 DOI: 10.1016/j.hbpd.2023.08.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2022] [Accepted: 08/21/2023] [Indexed: 09/01/2023]
Abstract
Acute pancreatitis is a common systemic inflammatory disease, manifested by a spectrum of severity, ranging from mild in the majority of patients to severe acute pancreatitis. Patients with severe acute pancreatitis suffer from severe local and systemic complications and organ failure, leading to a poor prognosis. The early recognition of the severe condition is important to improve prognosis. Obesity has risen in tandem with an increase in the severity of acute pancreatitis in recent years. Studies have revealed that adipose tissue, particularly visceral adipose tissue is associated with the prognosis of acute pancreatitis. This review discussed the role of visceral adipose tissue in obese patients with acute pancreatitis and explored the possible mechanism involved.
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Affiliation(s)
- Yuan Tian
- Department of Gastroenterology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing 102218, China
| | - Qing Huang
- Department of Gastroenterology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing 102218, China
| | - Yu-Tang Ren
- Department of Gastroenterology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing 102218, China
| | - Xuan Jiang
- Department of Gastroenterology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing 102218, China
| | - Bo Jiang
- Department of Gastroenterology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing 102218, China.
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8
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Diab R, Dimachkie L, Zein O, Dakroub A, Eid AH. Intermittent Fasting Regulates Metabolic Homeostasis and Improves Cardiovascular Health. Cell Biochem Biophys 2024; 82:1583-1597. [PMID: 38847940 PMCID: PMC11445340 DOI: 10.1007/s12013-024-01314-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/13/2024] [Indexed: 10/02/2024]
Abstract
Obesity is a leading cause of morbidity and mortality globally. While the prevalence of obesity has been increasing, the incidence of its related complications including dyslipidemia and cardiovascular disease (CVD) has also been rising. Recent research has focused on modalities aimed at reducing obesity. Several modalities have been suggested including behavioral and dietary changes, medications, and bariatric surgery. These modalities differ in their effectiveness and invasiveness, with dietary changes gaining more interest due to their minimal risks compared to other modalities. Specifically, intermittent fasting (IF) has been gaining interest in the past decade. IF is characterized by cycles of alternating fasting and eating windows, with several different forms practiced. IF has been shown to reduce weight and alleviate obesity-related complications. Our review of clinical and experimental studies explores the effects of IF on the lipid profile, white adipose tissue (WAT) dynamics, and the gut microbiome. Notably, IF corrects dyslipidemia, reduces WAT accumulation, and decreases inflammation, which reduces CVD and obesity. This comprehensive analysis details the protective metabolic role of IF, advocating for its integration into public health practices.
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Affiliation(s)
- Rawan Diab
- Faculty of Medicine, American University of Beirut Medical Center, Beirut, Lebanon
| | - Lina Dimachkie
- Faculty of Medicine, American University of Beirut Medical Center, Beirut, Lebanon
| | - Omar Zein
- Faculty of Medicine, American University of Beirut Medical Center, Beirut, Lebanon
| | - Ali Dakroub
- St. Francis Hospital and Heart Center, Roslyn, NY, USA
| | - Ali H Eid
- Department of Basic Medical Sciences, College of Medicine, Qatar University, QU Health, Doha, Qatar.
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Behrooz AB, Cordani M, Fiore A, Donadelli M, Gordon JW, Klionsky DJ, Ghavami S. The obesity-autophagy-cancer axis: Mechanistic insights and therapeutic perspectives. Semin Cancer Biol 2024; 99:24-44. [PMID: 38309540 DOI: 10.1016/j.semcancer.2024.01.003] [Citation(s) in RCA: 10] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2023] [Revised: 01/19/2024] [Accepted: 01/29/2024] [Indexed: 02/05/2024]
Abstract
Autophagy, a self-degradative process vital for cellular homeostasis, plays a significant role in adipose tissue metabolism and tumorigenesis. This review aims to elucidate the complex interplay between autophagy, obesity, and cancer development, with a specific emphasis on how obesity-driven changes affect the regulation of autophagy and subsequent implications for cancer risk. The burgeoning epidemic of obesity underscores the relevance of this research, particularly given the established links between obesity, autophagy, and various cancers. Our exploration delves into hormonal influence, notably INS (insulin) and LEP (leptin), on obesity and autophagy interactions. Further, we draw attention to the latest findings on molecular factors linking obesity to cancer, including hormonal changes, altered metabolism, and secretory autophagy. We posit that targeting autophagy modulation may offer a potent therapeutic approach for obesity-associated cancer, pointing to promising advancements in nanocarrier-based targeted therapies for autophagy modulation. However, we also recognize the challenges inherent to these approaches, particularly concerning their precision, control, and the dual roles autophagy can play in cancer. Future research directions include identifying novel biomarkers, refining targeted therapies, and harmonizing these approaches with precision medicine principles, thereby contributing to a more personalized, effective treatment paradigm for obesity-mediated cancer.
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Affiliation(s)
- Amir Barzegar Behrooz
- Department of Human Anatomy and Cell Science, University of Manitoba, College of Medicine, Winnipeg, Manitoba, Canada; Electrophysiology Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Marco Cordani
- Department of Biochemistry and Molecular Biology, School of Biology, Complutense University, Madrid, Spain; Instituto de Investigaciones Sanitarias San Carlos (IdISSC), Madrid, Spain
| | - Alessandra Fiore
- Department of Neurosciences, Biomedicine and Movement Sciences, Section of Biochemistry, University of Verona, Verona, Italy
| | - Massimo Donadelli
- Department of Neurosciences, Biomedicine and Movement Sciences, Section of Biochemistry, University of Verona, Verona, Italy
| | - Joseph W Gordon
- Department of Human Anatomy and Cell Science, University of Manitoba, College of Medicine, Winnipeg, Manitoba, Canada; Children Hospital Research Institute of Manitoba, University of Manitoba, Winnipeg, MB, Canada
| | - Daniel J Klionsky
- Life Sciences Institute and Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI, USA
| | - Saeid Ghavami
- Life Sciences Institute and Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI, USA; Faculty of Medicine in Zabrze, University of Technology in Katowice, 41-800 Zabrze, Poland; Research Institute of Oncology and Hematology, Cancer Care Manitoba-University of Manitoba, Winnipeg, Manitoba, Canada; Children Hospital Research Institute of Manitoba, University of Manitoba, Winnipeg, MB, Canada.
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10
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Engin A. Reappraisal of Adipose Tissue Inflammation in Obesity. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2024; 1460:297-327. [PMID: 39287856 DOI: 10.1007/978-3-031-63657-8_10] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/19/2024]
Abstract
Chronic low-grade inflammation is a central component in the pathogenesis of obesity-related expansion of adipose tissue and complications in other metabolic tissues. Five different signaling pathways are defined as dominant determinants of adipose tissue inflammation: These are increased circulating endotoxin due to dysregulation in the microbiota-gut-brain axis, systemic oxidative stress, macrophage accumulation, and adipocyte death. Finally, the nucleotide-binding and oligomerization domain (NOD) leucine-rich repeat family pyrin domain-containing 3 (NLRP3) inflammasome pathway is noted to be a key regulator of metabolic inflammation. The NLRP3 inflammasome and associated metabolic inflammation play an important role in the relationships among fatty acids and obesity. Several highly active molecules, including primarily leptin, resistin, adiponectin, visfatin, and classical cytokines, are abundantly released from adipocytes. The most important cytokines that are released by inflammatory cells infiltrating obese adipose tissue are tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), monocyte chemoattractant protein 1 (MCP-1) (CCL-2), and IL-1. All these molecules mentioned above act on immune cells, causing local and then general inflammation. Three metabolic pathways are noteworthy in the development of adipose tissue inflammation: toll-like receptor 4 (TLR4)/phosphatidylinositol-3'-kinase (PI3K)/Protein kinase B (Akt) signaling pathway, endoplasmic reticulum (ER) stress-derived unfolded protein response (UPR), and inhibitor of nuclear factor kappa-B kinase beta (IKKβ)-nuclear factor kappa B (NF-κB) pathway. In fact, adipose tissue inflammation is an adaptive response that contributes to a visceral depot barrier that effectively filters gut-derived endotoxin. Excessive fatty acid release worsens adipose tissue inflammation and contributes to insulin resistance. However, suppression of adipose inflammation in obesity with anti-inflammatory drugs is not a rational solution and paradoxically promotes insulin resistance, despite beneficial effects on weight gain. Inflammatory pathways in adipocytes are indeed indispensable for maintaining systemic insulin sensitivity. Cannabinoid type 1 receptor (CB1R) is important in obesity-induced pro-inflammatory response; however, blockade of CB1R, contrary to anti-inflammatory drugs, breaks the links between insulin resistance and adipose tissue inflammation. Obesity, however, could be decreased by improving leptin signaling, white adipose tissue browning, gut microbiota interactions, and alleviating inflammation. Furthermore, capsaicin synthesized by chilies is thought to be a new and promising therapeutic option in obesity, as it prevents metabolic endotoxemia and systemic chronic low-grade inflammation caused by high-fat diet.
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Affiliation(s)
- Atilla Engin
- Faculty of Medicine, Department of General Surgery, Gazi University, Besevler, Ankara, Turkey.
- Mustafa Kemal Mah. 2137. Sok. 8/14, 06520, Cankaya, Ankara, Turkey.
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11
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Medina A, Bruno J, Alemán JO. Metabolic flux analysis in adipose tissue reprogramming. IMMUNOMETABOLISM (COBHAM, SURREY) 2024; 6:e00039. [PMID: 38455681 PMCID: PMC10916752 DOI: 10.1097/in9.0000000000000039] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 05/08/2023] [Accepted: 01/29/2024] [Indexed: 03/09/2024]
Abstract
Obesity is a growing epidemic in the United States and worldwide and is associated with insulin resistance and cardiovascular disease, among other comorbidities. Understanding of the pathology that links overnutrition to these disease processes is ongoing. Adipose tissue is a heterogeneous organ comprised of multiple different cell types and it is likely that dysregulated metabolism within these cell populations disrupts both inter- and intracellular interactions and is a key driver of human disease. In recent years, metabolic flux analysis, which offers a precise quantification of metabolic pathway fluxes in biological systems, has emerged as a candidate strategy for uncovering the metabolic changes that stoke these disease processes. In this mini review, we discuss metabolic flux analysis as an experimental tool, with a specific emphasis on mass spectrometry with isotope tracing as this is the technique most frequently used for metabolic flux analysis in adipocytes. Furthermore, we examine existing literature that uses metabolic flux analysis to further our understanding of adipose tissue biology. Our group has a specific interest in understanding the role of white adipose tissue inflammation in the progression of cardiometabolic disease, as we know that in obesity the accumulation of pro-inflammatory adipose tissue macrophages is associated with significant morbidity, so we use this as a paradigm throughout our review for framing the application of these experimental techniques. However, there are many other biological applications to which they can be applied to further understanding of not only adipose tissue biology but also systemic homeostasis.
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Affiliation(s)
- Ashley Medina
- Laboratory of Translational Obesity Research, New York University Grossman School of Medicine, New York, NY, USA
- Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, New York University Grossman School of Medicine, New York, NY, USA
| | - Joanne Bruno
- Laboratory of Translational Obesity Research, New York University Grossman School of Medicine, New York, NY, USA
- Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, New York University Grossman School of Medicine, New York, NY, USA
| | - José O. Alemán
- Laboratory of Translational Obesity Research, New York University Grossman School of Medicine, New York, NY, USA
- Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, New York University Grossman School of Medicine, New York, NY, USA
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12
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Kiyak U, Urganci N, Usta M. Assesment of functional gastrointestinal diseases in obese children. Eur J Pediatr 2023; 182:4949-4955. [PMID: 37606702 DOI: 10.1007/s00431-023-05165-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2023] [Revised: 08/14/2023] [Accepted: 08/16/2023] [Indexed: 08/23/2023]
Abstract
UNLABELLED Functional gastrointestinal disorders (FGID) are disorders of gut-brain interactions characterized by chronic recurrent gastrointestinal symptoms and are reported to be more common in obese individuals. The aim of the study was to evaluate FGID in obese children. A total of 405 children (6-18 years) were enrolled in this cross sectional study. The children were divided into two groups according to body mass index (BMI) as < 85th percentile and > 95th percentile. Diagnosis of FGID was based on ROME VI criteria. Demographic and clinical characteristics of the patients were evaluated. FGID and subgroups were determined. The mean age of the children was 12.73 ± 3.17 years; 52% (n = 211) of them was female and 47.9% (n = 194) was male. A total of 50.6% patients had BMI > 95th percentile, and 55.1% of those patients had FGID. The subgroups of FGID, functional abdominal pain disorders and functional defecation disorders were significantly more common in obese children than non-obese group (P < 0.01). Additionally, constipation-predominant irritable bowel syndrome (IBS), diarrhea-predominant IBS, functional diarrhea, and abdominal distention were significantly more common in obese children than non-obese children (P < 0.01). CONCLUSION FGID in obese children was found to be increased significantly. Assessment of functional gastrointestinal symptoms in obese children will prevent unnecessary examinations. WHAT IS KNOWN • Functional gastrointestinal disorders are reported to be more common in obese individuals. WHAT IS NEW • Functional abdominal pain disorders and functional defecation disorders were significantly more common in obese children than non-obese group. • Constipation-predominant irritable bowel syndrome (IBS), diarrhea-predominant IBS, functional diarrhea, and abdominal distention were significantly more common in obese children than non-obese children.
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Affiliation(s)
- Umit Kiyak
- SBU Sisli Hamidiye Etfal Training and Research Hospital, Pediatrics, MD, Istanbul, Turkey
| | - Nafiye Urganci
- Division of Pediatric Gastroenterology, SBU Sisli Hamidiye Etfal Training and Research Hospital, Kazim Karabekir Pasa, Bahcekoy No: 62 Sariyer, Istanbul, Turkey.
| | - Merve Usta
- Division of Pediatric Gastroenterology, SBU Sisli Hamidiye Etfal Training and Research Hospital, Kazim Karabekir Pasa, Bahcekoy No: 62 Sariyer, Istanbul, Turkey
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13
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Aziz C, Morales A, Pinto W, Fanchini V, Dell Aquila L, Sangaleti C, Elias R, Dalboni M. Evaluation of IL-6, FoxP3 Treg lymphocytes, intestinal barrier biomarkers and the use of synbiotics in obese adolescents: a pilot study. Front Pediatr 2023; 11:1215793. [PMID: 37859769 PMCID: PMC10583575 DOI: 10.3389/fped.2023.1215793] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2023] [Accepted: 09/19/2023] [Indexed: 10/21/2023] Open
Abstract
Aim This prospective pilot study evaluated inflammatory and intestinal barrier biomarkers and the effects of a synbiotic in obese adolescents. Methods Eighteen obese and 20 eutrophic adolescents were evaluated for body composition using bioimpedance analysis (BIA), body mass index (BMI), IL-6 and lipopolysaccharide (LPS) serum levels, CD4 and FoxP3 Treg lymphocytes and monocytes. Synbiotic supplementation for 60 days was also evaluated for these parameters only in obese adolescents. Results We observed an increase in CD4 lymphocyte (18.0 ± 12.4 vs. 8.9 ± 7.5; p < 0.01), IL-6 (0.30 ± 0.06 vs. 0.20 ± 0.06; p = 0.02) and LPS (0.18 ± 0.15 vs. 0.08 ± 0.05; p < 0.01) levels in obese compared to eutrophic adolescents. After synbiotic supplementation, FoxP3 Treg lymphocytes increased (14.0 ± 6.7 vs. 9.9 ± 5.4; p = 0.02) in obese adolescents. Conclusions Obese adolescents presented a state of microinflammation and intestinal barrier breakdown, and synbiotic supplementation increased the expression of FoxP3 Treg lymphocytes, an anti-inflammatory regulator. Whether the increase in FoxP3 Treg lymphocytes may have an impact on inflammation and outcomes in obese adolescents deserves further evaluation.
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Affiliation(s)
- Cylmara Aziz
- Department of Postgraduate Studies in Medicine, Universidade Nove de Julho, São Paulo, Brazil
| | - Armando Morales
- Department of Postgraduate Studies in Medicine, Universidade Nove de Julho, São Paulo, Brazil
| | - Walter Pinto
- Department of Postgraduate Studies in Medicine, Universidade Nove de Julho, São Paulo, Brazil
| | - Vanessa Fanchini
- Department of Postgraduate Studies in Medicine, Universidade Nove de Julho, São Paulo, Brazil
| | - Luis Dell Aquila
- Department of Postgraduate Studies in Medicine, Universidade Nove de Julho, São Paulo, Brazil
| | - Carine Sangaleti
- Department of Postgraduate Studies in Nanosciences and Biosciences, Universidade Estadual do Centro Oeste, Guarapuava, Brazil
| | - Rosilene Elias
- Department of Postgraduate Studies in Medicine, Universidade Nove de Julho, São Paulo, Brazil
| | - Maria Dalboni
- Department of Postgraduate Studies in Medicine, Universidade Nove de Julho, São Paulo, Brazil
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14
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Ford H, Liu Q, Fu X, Strieder-Barboza C. White Adipose Tissue Heterogeneity in the Single-Cell Era: From Mice and Humans to Cattle. BIOLOGY 2023; 12:1289. [PMID: 37886999 PMCID: PMC10604679 DOI: 10.3390/biology12101289] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/02/2023] [Revised: 09/19/2023] [Accepted: 09/22/2023] [Indexed: 10/28/2023]
Abstract
Adipose tissue is a major modulator of metabolic function by regulating energy storage and by acting as an endocrine organ through the secretion of adipokines. With the advantage of next-generation sequencing-based single-cell technologies, adipose tissue has been studied at single-cell resolution, thus providing unbiased insight into its molecular composition. Recent single-cell RNA sequencing studies in human and mouse models have dissected the transcriptional cellular heterogeneity of subcutaneous (SAT), visceral (VAT), and intramuscular (IMAT) white adipose tissue depots and revealed unique populations of adipose tissue progenitor cells, mature adipocytes, immune cell, vascular cells, and mesothelial cells that play direct roles on adipose tissue function and the development of metabolic disorders. In livestock species, especially in bovine, significant gaps of knowledge remain in elucidating the roles of adipose tissue cell types and depots on driving the pathogenesis of metabolic disorders and the distinct fat deposition in VAT, SAT, and IMAT in meat animals. This review summarizes the current knowledge on the transcriptional and functional cellular diversity of white adipose tissue revealed by single-cell approaches and highlights the depot-specific function of adipose tissue in different mammalian species, with a particular focus on recent findings and future implications in cattle.
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Affiliation(s)
- Hunter Ford
- Department of Veterinary Sciences, Davis College of Agricultural Sciences and Natural Resources, Texas Tech University, Lubbock, TX 79409, USA;
| | - Qianglin Liu
- School of Animal Sciences, Agricultural Center, Louisiana State University, Baton Rouge, LA 70803, USA; (Q.L.); (X.F.)
| | - Xing Fu
- School of Animal Sciences, Agricultural Center, Louisiana State University, Baton Rouge, LA 70803, USA; (Q.L.); (X.F.)
| | - Clarissa Strieder-Barboza
- Department of Veterinary Sciences, Davis College of Agricultural Sciences and Natural Resources, Texas Tech University, Lubbock, TX 79409, USA;
- School of Veterinary Medicine, Texas Tech University, Amarillo, TX 79106, USA
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15
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Rashid M, Kondoh K, Palfalvi G, Nakajima KI, Minokoshi Y. Inhibition of high-fat diet-induced inflammatory responses in adipose tissue by SF1-expressing neurons of the ventromedial hypothalamus. Cell Rep 2023; 42:112627. [PMID: 37339627 DOI: 10.1016/j.celrep.2023.112627] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2022] [Revised: 03/27/2023] [Accepted: 05/24/2023] [Indexed: 06/22/2023] Open
Abstract
Inflammation and thermogenesis in white adipose tissue (WAT) at different sites influence the overall effects of obesity on metabolic health. In mice fed a high-fat diet (HFD), inflammatory responses are less pronounced in inguinal WAT (ingWAT) than in epididymal WAT (epiWAT). Here we show that ablation and activation of steroidogenic factor 1 (SF1)-expressing neurons in the ventromedial hypothalamus (VMH) oppositely affect the expression of inflammation-related genes and the formation of crown-like structures by infiltrating macrophages in ingWAT, but not in epiWAT, of HFD-fed mice, with these effects being mediated by sympathetic nerves innervating ingWAT. In contrast, SF1 neurons of the VMH preferentially regulated the expression of thermogenesis-related genes in interscapular brown adipose tissue (BAT) of HFD-fed mice. These results suggest that SF1 neurons of the VMH differentially regulate inflammatory responses and thermogenesis among various adipose tissue depots and restrain inflammation associated with diet-induced obesity specifically in ingWAT.
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Affiliation(s)
- Misbah Rashid
- Division of Endocrinology and Metabolism, Department of Homeostatic Regulation, National Institute for Physiological Sciences, National Institutes of Natural Sciences, Okazaki, Aichi 444-8585, Japan; Graduate Institute for Advanced Studies, SOKENDAI, Okazaki, Aichi 444-8585, Japan
| | - Kunio Kondoh
- Division of Endocrinology and Metabolism, Department of Homeostatic Regulation, National Institute for Physiological Sciences, National Institutes of Natural Sciences, Okazaki, Aichi 444-8585, Japan; Graduate Institute for Advanced Studies, SOKENDAI, Okazaki, Aichi 444-8585, Japan.
| | - Gergo Palfalvi
- Division of Evolutionary Biology, National Institute for Basic Biology, National Institutes of Natural Sciences, Okazaki, Aichi 444-8585, Japan
| | - Ken-Ichiro Nakajima
- Division of Endocrinology and Metabolism, Department of Homeostatic Regulation, National Institute for Physiological Sciences, National Institutes of Natural Sciences, Okazaki, Aichi 444-8585, Japan; Graduate Institute for Advanced Studies, SOKENDAI, Okazaki, Aichi 444-8585, Japan
| | - Yasuhiko Minokoshi
- Division of Endocrinology and Metabolism, Department of Homeostatic Regulation, National Institute for Physiological Sciences, National Institutes of Natural Sciences, Okazaki, Aichi 444-8585, Japan; Graduate Institute for Advanced Studies, SOKENDAI, Okazaki, Aichi 444-8585, Japan.
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16
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Hameed M, Geerling E, Pinto AK, Miraj I, Weger-Lucarelli J. Immune response to arbovirus infection in obesity. Front Immunol 2022; 13:968582. [PMID: 36466818 PMCID: PMC9716109 DOI: 10.3389/fimmu.2022.968582] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2022] [Accepted: 11/04/2022] [Indexed: 12/26/2023] Open
Abstract
Obesity is a global health problem that affects 650 million people worldwide and leads to diverse changes in host immunity. Individuals with obesity experience an increase in the size and the number of adipocytes, which function as an endocrine organ and release various adipocytokines such as leptin and adiponectin that exert wide ranging effects on other cells. In individuals with obesity, macrophages account for up to 40% of adipose tissue (AT) cells, three times more than in adipose tissue (10%) of healthy weight individuals and secrete several cytokines and chemokines such as interleukin (IL)-1β, chemokine C-C ligand (CCL)-2, IL-6, CCL5, and tumor necrosis factor (TNF)-α, leading to the development of inflammation. Overall, obesity-derived cytokines strongly affect immune responses and make patients with obesity more prone to severe symptoms than patients with a healthy weight. Several epidemiological studies reported a strong association between obesity and severe arthropod-borne virus (arbovirus) infections such as dengue virus (DENV), chikungunya virus (CHIKV), West Nile virus (WNV), and Sindbis virus (SINV). Recently, experimental investigations found that DENV, WNV, CHIKV and Mayaro virus (MAYV) infections cause worsened disease outcomes in infected diet induced obese (DIO) mice groups compared to infected healthy-weight animals. The mechanisms leading to higher susceptibility to severe infections in individuals with obesity remain unknown, though a better understanding of the causes will help scientists and clinicians develop host directed therapies to treat severe disease. In this review article, we summarize the effects of obesity on the host immune response in the context of arboviral infections. We have outlined that obesity makes the host more susceptible to infectious agents, likely by disrupting the functions of innate and adaptive immune cells. We have also discussed the immune response of DIO mouse models against some important arboviruses such as CHIKV, MAYV, DENV, and WNV. We can speculate that obesity-induced disruption of innate and adaptive immune cell function in arboviral infections ultimately affects the course of arboviral disease. Therefore, further studies are needed to explore the cellular and molecular aspects of immunity that are compromised in obesity during arboviral infections or vaccination, which will be helpful in developing specific therapeutic/prophylactic interventions to prevent immunopathology and disease progression in individuals with obesity.
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Affiliation(s)
- Muddassar Hameed
- Department of Biomedical Sciences and Pathobiology, VA-MD Regional College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, United States
| | - Elizabeth Geerling
- Department of Molecular Microbiology and Immunology, Saint Louis University, St. Louis, MO, United States
| | - Amelia K. Pinto
- Department of Molecular Microbiology and Immunology, Saint Louis University, St. Louis, MO, United States
| | - Iqra Miraj
- College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou, China
| | - James Weger-Lucarelli
- Department of Biomedical Sciences and Pathobiology, VA-MD Regional College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, United States
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17
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Abstract
Lifestyle factors are modifiable behavioral factors that have a significant impact on health and longevity. Diet-induced obesity and physical activity/exercise are two prevalent lifestyle factors that have strong relationships to overall health. The mechanisms linking obesity to negative health outcomes and the mechanisms linking increased participation in physical activity/exercise to positive health outcomes are beginning to be elucidated. Chronic inflammation, due in part to overproduction of myeloid cells from hematopoietic stem cells (HSCs) in the bone marrow, is an established mechanism responsible for the negative health effects of obesity. Recent work has shown that exercise training can reverse the aberrant myelopoiesis present in obesity in part by restoring the bone marrow microenvironment. Specifically, exercise training reduces marrow adipose tissue, increases HSC retention factor expression, and reduces pro-inflammatory cytokine levels in the bone marrow. Other, novel mechanistic factors responsible for these exercise-induced effects, including intercellular communication using extracellular vesicles (EVs), is beginning to be explored. This review will summarize the recent literature describing the effects of exercise on hematopoiesis in individuals with obesity and introduce the potential contribution of EVs to this process.
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18
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Exploring Lead loci shared between schizophrenia and Cardiometabolic traits. BMC Genomics 2022; 23:617. [PMID: 36008755 PMCID: PMC9414090 DOI: 10.1186/s12864-022-08766-4] [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: 01/16/2022] [Accepted: 07/13/2022] [Indexed: 11/10/2022] Open
Abstract
Individuals with schizophrenia (SCZ) have, on average, a 10- to 20-year shorter expected life span than the rest of the population, primarily due to cardiovascular disease comorbidity. Genome-wide association studies (GWAS) have previously been used to separately identify common variants in SCZ and cardiometabolic traits. However, genetic variants jointly influencing both traits remain to be fully characterised. To assess overlaps (if any) between the genetic architecture of SCZ and cardiometabolic traits, we used conditional false discovery rate (FDR) and local genetic correlation statistical framework analyses. A conjunctional FDR was used to identify shared genetic traits between SCZ and cardiometabolic risk factors. We identified 144 genetic variants which were shared between SCZ and body mass index (BMI), and 15 variants shared between SCZ and triglycerides (TG). Furthermore, we discovered four novel single nucleotide polymorphisms (SNPs) (rs3865350, rs9860913, rs13307 and rs9614186) and four proximate genes (DERL2, SNX4, LY75 and EFCAB6) which were shared by SCZ and BMI. We observed that the novel genetic variant rs13307 and the most proximate gene LY75 exerted potential effects on SCZ and BMI comorbidity. Also, we observed a mixture of concordant and opposite direction associations with shared genetic variants. We demonstrated a moderate to high genetic overlap between SCZ and cardiometabolic traits associated with a pattern of bidirectional associations. Our data suggested a complex interplay between metabolism-related gene pathways in SCZ pathophysiology.
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19
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New Insights into Adipokines in Gestational Diabetes Mellitus. Int J Mol Sci 2022; 23:ijms23116279. [PMID: 35682958 PMCID: PMC9181219 DOI: 10.3390/ijms23116279] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2022] [Revised: 05/27/2022] [Accepted: 06/01/2022] [Indexed: 12/12/2022] Open
Abstract
Gestational diabetes mellitus (GDM) is the most common metabolic disorder of pregnancy and has considerable short- and long-term consequences for the health of both the mother and the newborn. Within its pathophysiology, genetic, nutritional, epigenetic, immunological, and hormonal components have been described. Within the last two items, it is known that different hormones and cytokines secreted by adipose tissue, known collectively as adipokines, are involved in the metabolic alterations underlying GDM. Although the maternal circulating profile of adipokines in GDM has been extensively studied, and there are excellent reviews on the subject, it is in recent years that more progress has been made in the study of their expression in visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), placenta, and their concentrations in the umbilical circulation. Thus, this review compiles and organizes the most recent findings on the maternal and umbilical circulating profile and the levels of expression of adipokines in VAT, SAT, and placenta in GDM.
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20
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Jabbour J, Rahme M, Mahfoud ZR, El-Hajj Fuleihan G. Effect of high dose vitamin D supplementation on indices of sarcopenia and obesity assessed by DXA among older adults: A randomized controlled trial. Endocrine 2022; 76:162-171. [PMID: 35028890 DOI: 10.1007/s12020-021-02951-3] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2021] [Accepted: 11/15/2021] [Indexed: 01/11/2023]
Abstract
BACKGROUND Hypovitaminosis D is associated with Sarcopenic Obesity (SO), but evidence from randomized Vitamin D 3 (VD3) trials is scarce. OBJECTIVE Compare the effect of VD3 supplementation, at two doses, on SO indices at 12 months. METHODS Overweight older adults (>65 years) with baseline 25-hydroxyvitamin D (25OHD) of 10-30 ng/mL were recruited in this double-blind, randomized, controlled multicenter trial (clinicaltrial.gov identifier: NCT01315366). All subjects received 1000 mg calcium citrate/day and underwent total body Dual-energy X-ray Absorptiometry for body composition assessment. Low Dose Group (LDG) and High Dose Group (HDG) received 600 IU -Institute of Medicine (IOM) Recommended Dietary Allowance (RDA)- and 3750 IU VD3/day, respectively. RESULTS Mean age was 71 ± 4.6 years, 55% females, BMI: 30.2 ± 4.5 Kg/m2, and 43% had metabolic syndrome. There were no differences in baseline characteristics between groups. At 12 months, 248 participants had body composition data, 122 in LDG and 126 in HDG. Proportions of patients with diminished muscle mass, muscle strength, and visceral adiposity did not differ between the 2 groups at baseline or 12 months. Similarly, no significant differences were noted in the proportion of patients with SO at study entry (1.8% in LDG vs 1.6% HDG; p = 0.99) and at 12 months (3.7% in LDG vs. 0.9% HDG; p = 0.18) across arms. CONCLUSIONS Weekly VD3, at the daily equivalent of 3750 IU/day, did not improve indices of sarcopenia nor adiposity compared to the IOM RDA dose in adults.
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Affiliation(s)
- Jana Jabbour
- Department of Nutrition, School of Health Sciences, Modern University for Business and Sciences, Beirut, Lebanon
| | - Maya Rahme
- Department of Internal Medicine, Division of Endocrinology, Calcium Metabolism and Osteoporosis Program, WHO Collaborating Center for Metabolic Bone Disorders, American University of Beirut Medical Center, Beirut, Lebanon
| | - Ziyad R Mahfoud
- Department of Medical Education, Weill Cornell Medicine, Doha, Qatar
- Department of Population Health Sciences, Division of Epidemiology, Weill Cornell Medicine, New York, NY, USA
| | - Ghada El-Hajj Fuleihan
- Department of Internal Medicine, Division of Endocrinology, Calcium Metabolism and Osteoporosis Program, WHO Collaborating Center for Metabolic Bone Disorders, American University of Beirut Medical Center, Beirut, Lebanon.
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21
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Mohr AE, Crawford M, Jasbi P, Fessler S, Sweazea KL. Lipopolysaccharide and the gut microbiota: Considering structural variation. FEBS Lett 2022; 596:849-875. [PMID: 35262962 DOI: 10.1002/1873-3468.14328] [Citation(s) in RCA: 65] [Impact Index Per Article: 21.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2021] [Revised: 02/16/2022] [Accepted: 02/17/2022] [Indexed: 11/10/2022]
Abstract
Systemic inflammation is associated with chronic disease and is purported to be a main pathogenic mechanism underlying metabolic conditions. Microbes harbored in the host gastrointestinal tract release signaling byproducts from their cell wall, such as lipopolysaccharides (LPS), which can act locally and, after crossing the gut barrier and entering circulation, also systemically. Defined as metabolic endotoxemia, elevated concentrations of LPS in circulation are associated with metabolic conditions and chronic disease. As such, measurement of LPS is highly prevalent in animal and human research investigating these states. Indeed, LPS can be a potent stimulant of host immunity but this response depends on the microbial species' origin, a parameter often overlooked in both preclinical and clinical investigations. Indeed, the lipid A portion of LPS is mutable and comprises the main virulence and endotoxic component, thus contributing to the structural and functional diversity among LPSs from microbial species. In this review, we discuss how such structural differences in LPS can induce differential immunological responses in the host.
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Affiliation(s)
- Alex E Mohr
- College of Health Solutions, Arizona State University, Phoenix, Arizona, United States of America
| | - Meli'sa Crawford
- Biomedical Sciences, University of Riverside, California, Riverside, California, United States of America
| | - Paniz Jasbi
- College of Health Solutions, Arizona State University, Phoenix, Arizona, United States of America
| | - Samantha Fessler
- College of Health Solutions, Arizona State University, Phoenix, Arizona, United States of America
| | - Karen L Sweazea
- College of Health Solutions, Arizona State University, Phoenix, Arizona, United States of America.,School of Life Sciences, Arizona State University, Tempe, Arizona, United States of America
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22
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Thakkar N, Shin YB, Sung HK. Nutritional Regulation of Mammary Tumor Microenvironment. Front Cell Dev Biol 2022; 10:803280. [PMID: 35186923 PMCID: PMC8847692 DOI: 10.3389/fcell.2022.803280] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2021] [Accepted: 01/12/2022] [Indexed: 12/12/2022] Open
Abstract
The mammary gland is a heterogeneous organ comprising of immune cells, surrounding adipose stromal cells, vascular cells, mammary epithelial, and cancer stem cells. In response to nutritional stimuli, dynamic interactions amongst these cell populations can be modulated, consequently leading to an alteration of the glandular function, physiology, and ultimately disease pathogenesis. For example, obesity, a chronic over-nutritional condition, is known to disrupt homeostasis within the mammary gland and increase risk of breast cancer development. In contrast, emerging evidence has demonstrated that fasting or caloric restriction can negatively impact mammary tumorigenesis. However, how fasting induces phenotypic and functional population differences in the mammary microenvironment is not well understood. In this review, we will provide a detailed overview on the effect of nutritional conditions (i.e., overnutrition or fasting) on the mammary gland microenvironment and its impact on mammary tumor progression.
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Affiliation(s)
- Nikita Thakkar
- Translational Medicine Program, The Hospital for Sick Children, Toronto, ON, Canada
- Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada
| | - Ye Bin Shin
- Translational Medicine Program, The Hospital for Sick Children, Toronto, ON, Canada
| | - Hoon-Ki Sung
- Translational Medicine Program, The Hospital for Sick Children, Toronto, ON, Canada
- Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada
- *Correspondence: Hoon-Ki Sung,
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23
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Palano MT, Cucchiara M, Gallazzi M, Riccio F, Mortara L, Gensini GF, Spinetti G, Ambrosio G, Bruno A. When a Friend Becomes Your Enemy: Natural Killer Cells in Atherosclerosis and Atherosclerosis-Associated Risk Factors. Front Immunol 2022; 12:798155. [PMID: 35095876 PMCID: PMC8793801 DOI: 10.3389/fimmu.2021.798155] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2021] [Accepted: 12/14/2021] [Indexed: 12/15/2022] Open
Abstract
Atherosclerosis (ATS), the change in structure and function of arteries with associated lesion formation and altered blood flow, is the leading cause of cardiovascular disease, the number one killer worldwide. Beyond dyslipidemia, chronic inflammation, together with aberrant phenotype and function of cells of both the innate and adaptive immune system, are now recognized as relevant contributors to atherosclerosis onset and progression. While the role of macrophages and T cells in atherosclerosis has been addressed in several studies, Natural Killer cells (NKs) represent a poorly explored immune cell type, that deserves attention, due to NKs’ emerging contribution to vascular homeostasis. Furthermore, the possibility to re-polarize the immune system has emerged as a relevant tool to design new therapies, with some succesfull exmples in the field of cancer immunotherapy. Thus, a deeper knowledge of NK cell pathophysiology in the context of atherosclerosis and atherosclerosis-associated risk factors could help developing new preventive and treatment strategies, and decipher the complex scenario/history from “the risk factors for atherosclerosis” Here, we review the current knowledge about NK cell phenotype and activities in atherosclerosis and selected atherosclerosis risk factors, namely type-2 diabetes and obesity, and discuss the related NK-cell oriented environmental signals.
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Affiliation(s)
- Maria Teresa Palano
- Laboratory of Innate Immunity, Unit of Molecular Pathology, Biochemistry and Immunology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) MultiMedica, Milano, Italy
| | - Martina Cucchiara
- Laboratory of Immunology and General Pathology, Department of Biotechnology and Life Sciences, University of Insubria, Varese, Italy
| | - Matteo Gallazzi
- Laboratory of Immunology and General Pathology, Department of Biotechnology and Life Sciences, University of Insubria, Varese, Italy
| | - Federica Riccio
- Laboratory of Cardiovascular Physiopathology-Regenerative Medicine, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) MultiMedica, Milano, Italy
| | - Lorenzo Mortara
- Laboratory of Immunology and General Pathology, Department of Biotechnology and Life Sciences, University of Insubria, Varese, Italy
| | - Gian Franco Gensini
- Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) MultiMedica, Milano, Italy
| | - Gaia Spinetti
- Laboratory of Cardiovascular Physiopathology-Regenerative Medicine, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) MultiMedica, Milano, Italy
| | | | - Antonino Bruno
- Laboratory of Innate Immunity, Unit of Molecular Pathology, Biochemistry and Immunology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) MultiMedica, Milano, Italy
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Ashrafian F, Keshavarz Azizi Raftar S, Shahryari A, Behrouzi A, Yaghoubfar R, Lari A, Moradi HR, Khatami S, Omrani MD, Vaziri F, Masotti A, Siadat SD. Comparative effects of alive and pasteurized Akkermansia muciniphila on normal diet-fed mice. Sci Rep 2021; 11:17898. [PMID: 34504116 PMCID: PMC8429653 DOI: 10.1038/s41598-021-95738-5] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2021] [Accepted: 07/20/2021] [Indexed: 02/08/2023] Open
Abstract
Recently, Akkermansia muciniphila an anaerobic member of the gut microbiota, has been proposed as a next-generation probiotic. The aim of this study was evaluation of the effect of alive and pasteurized A. muciniphila on health status, intestinal integrity, immune response, lipid metabolism, and gut microbial composition in normal-diet fed mice as well as direct effects of the bacterium on Caco-2 cell line. A total of 30 mice were distributed into three different groups, control, alive, and pasteurized A. muciniphila-treated group. After acclimation, control and treatment groups were administrated with PBS and 109 CFU/200µL of bacterial suspension for 5 weeks, respectively. Besides, Caco-2 separately exposed to alive, pasteurized A. muciniphila and PBS for 24 h. The results showed that administration of A. muciniphila leads to reduction in body, liver, and white adipose weight. Histology data revealed both treatments had no adverse effects in colon, liver, and adipose tissues as well as induced better gut structure. Moreover, biochemical parameters and inflammatory biomarkers in plasma demonstrated that pasteurized A. muciniphila had more pronounce effect. Furthermore, alive A. muciniphia had better effects on the modulation of gene expression related to fatty acid synthesis, energy homeostasis, and immune response in the liver; meanwhile, these effects in the adipose was more in the pasteurized A. muciniphila administration. More importantly, the improvement of gut health by enhancing strengthen intestinal integrity and maintaining immune homeostasis was seen in both treatments; notably, pasteurized A. muciniphila had more effective. Similarly, treatment with the pasteurized form more effectively upregulated tight junction and regulated immune response-related genes in Caco-2 cell line. Both treatments triggered the improvement of microbiota communities, particularly the alive form. Therefore, both forms of A. muciniphila could modulate lipid and immune homeostasis, improved some gut microbiota, and promoted the overall health, while all these effects were dominantly observed in pasteurized form. In conclusion, pasteurized A. muciniphila can be considered as new medical supplement to maintain health state and prevent diseases in normal mice through different mechanisms.
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Affiliation(s)
- Fatemeh Ashrafian
- grid.420169.80000 0000 9562 2611Microbiology Research Center (MRC), Pasteur Institute of Iran, Tehran, Iran ,grid.420169.80000 0000 9562 2611Clinical Research Department, Pasteur Institute of Iran, Tehran, Iran
| | | | - Arefeh Shahryari
- grid.420169.80000 0000 9562 2611Microbiology Research Center (MRC), Pasteur Institute of Iran, Tehran, Iran
| | - Ava Behrouzi
- grid.420169.80000 0000 9562 2611Microbiology Research Center (MRC), Pasteur Institute of Iran, Tehran, Iran ,grid.411463.50000 0001 0706 2472Department of Microbiology, Faculty of Advanced Science and Technology, Tehran Medical Science, Islamic Azad University, Tehran, Iran
| | - Rezvan Yaghoubfar
- grid.420169.80000 0000 9562 2611Microbiology Research Center (MRC), Pasteur Institute of Iran, Tehran, Iran
| | - Arezou Lari
- grid.420169.80000 0000 9562 2611Systems Biomedicine Unit, Pasteur Institute of Iran, Tehran, Iran
| | - Hamid Reza Moradi
- grid.412573.60000 0001 0745 1259Department of Basic Sciences, School of Veterinary Medicine, Shiraz University, Shiraz, Iran
| | - Shohreh Khatami
- grid.420169.80000 0000 9562 2611Biochemistry Department, Pasteur Institute of Iran, Tehran, Iran
| | - Mir Davood Omrani
- grid.411600.2Department of Medical Genetics, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Farzam Vaziri
- grid.420169.80000 0000 9562 2611Microbiology Research Center (MRC), Pasteur Institute of Iran, Tehran, Iran ,grid.420169.80000 0000 9562 2611Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, Tehran, Iran
| | - Andrea Masotti
- grid.414125.70000 0001 0727 6809Research Laboratories, Children’s Hospital Bambino Gesù-IRCCS, Rome, Italy
| | - Seyed Davar Siadat
- grid.420169.80000 0000 9562 2611Microbiology Research Center (MRC), Pasteur Institute of Iran, Tehran, Iran ,grid.420169.80000 0000 9562 2611Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, Tehran, Iran
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Li Y, Gan M, Tang T, Shao J, Lai T, Ma Y, Elzo MA, Jia X, Hu S, Wang J, Lai S. Intramuscular adipocyte and fatty acid differences between high-fat and control rabbit groups subject to a restricted diet. Vet Med Sci 2021; 7:2051-2060. [PMID: 34273256 PMCID: PMC8464271 DOI: 10.1002/vms3.576] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023] Open
Abstract
Fatty acids of intramuscular fat (IMF) in rabbits can influence meat quality, but it is unclear which fatty acids benefit to human health. A rabbit model of weight gain and weight loss was constructed using two rabbit groups and two growth stages. Stage 1 included control group1 fed a commercial diet(CG1) and experimental group1 fed a high fat diet (EG1). Stage 2 include control group2(CG2) and experimental group2 (EG2) both fed a restricted commercial diet. We detected differences in blood biochemical indicators as well as changes in intramuscular adipose cells and intramuscular fatty acid content in control and experiment groups at two stages. High fat induction can make rabbits become obese, have higher concentrations of glucose (GLU), total cholesterol (TC), triglyceride (TG), low density lipoprotein-cholesterol (LDL-C) and free fatty acid (FFA), and lower concentrations of insulin (INS). In addition, a high-fat diet promotes hypertrophy of precursor adipocytes in femoral muscles. Conversely, a restricted diet causes weight loss, decreases the concentration of TG, FFA, and INS in CG2 and EG2, and increases the deposition of unsaturated fatty acids in the femoral muscle. The content of monounsaturated trans oleic acid (C18:1n-9T) in EG2 was significantly higher than in CG2, whereas oleic acid (C18:1n-9C) was significantly lower in EG2 than in CG2. The polyunsaturated fatty acids Linolenate (C18:3 n-3) and cis-5,8,11,14,17-Eicosapentaenoate (C20:5 n-3) increased in CG2 and EG2. The content of Linoleate (C18:2 n-6) and γ-Linolenic acid (C18:3 n-6) significantly increased in CG2. The content of cis-11,14-Eicosatrienoic acid (C20:2) decreased significantly in CG2, but increased significantly in EG2.Thus, a high-fat diet can increase the formation of unhealthy fatty acids. Conversely, weight loss due to a restricted diet leads to an increase in unsaturated fatty acids in the femoral muscle, indicating that it reduces obesity symptoms and it may improve meat quality in rabbit.
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Affiliation(s)
- YanHong Li
- College of Animal Science and Technology, Sichuan Agricultural University-Chengdu Campus, Chengdu, Sichuan, P. R. China
| | - Mingchuan Gan
- College of Animal Science and Technology, Sichuan Agricultural University-Chengdu Campus, Chengdu, Sichuan, P. R. China
| | - Tao Tang
- College of Animal Science and Technology, Sichuan Agricultural University-Chengdu Campus, Chengdu, Sichuan, P. R. China
| | - Jiahao Shao
- College of Animal Science and Technology, Sichuan Agricultural University-Chengdu Campus, Chengdu, Sichuan, P. R. China
| | - Tianfu Lai
- College of Animal Science and Technology, Sichuan Agricultural University-Chengdu Campus, Chengdu, Sichuan, P. R. China
| | - Yuan Ma
- College of Animal Science and Technology, Sichuan Agricultural University-Chengdu Campus, Chengdu, Sichuan, P. R. China
| | - Mauricio A Elzo
- Department of Animal Sciences, University of Florida, Gainesville, Florida, USA
| | - Xianbo Jia
- College of Animal Science and Technology, Sichuan Agricultural University-Chengdu Campus, Chengdu, Sichuan, P. R. China
| | - Shenqiang Hu
- College of Animal Science and Technology, Sichuan Agricultural University-Chengdu Campus, Chengdu, Sichuan, P. R. China
| | - Jie Wang
- College of Animal Science and Technology, Sichuan Agricultural University-Chengdu Campus, Chengdu, Sichuan, P. R. China
| | - SongJia Lai
- College of Animal Science and Technology, Sichuan Agricultural University-Chengdu Campus, Chengdu, Sichuan, P. R. China
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Effects of short-term calorie restriction on circulating DPP-4/sCD26 concentrations and body composition in patients with type 2 diabetes. Diabetol Int 2021; 12:286-292. [PMID: 34150437 DOI: 10.1007/s13340-020-00485-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2020] [Accepted: 12/09/2020] [Indexed: 10/22/2022]
Abstract
Previous studies have shown that dipeptidyl peptidase (DPP)-4, is released from adipocytes in a differentiation-dependent manner and a marker for insulin resistance in obese individuals who have particularly high circulating DPP-4/soluble CD26 (sCD26) concentrations. In this study, we have evaluated the effects of short-term hospitalization with calorie restriction on body composition and circulating DPP-4/sCD26 concentrations in patients with type 2 diabetes. A total of 47 Japanese adults with type 2 diabetes were recruited to the study (age; 56.6 ± 13.0 years, body mass index (BMI); 27.3 ± 5.6 kg/m2). Body composition, circulating DPP-4/sCD26 concentrations and metabolic parameters were assessed upon admission and at discharge from hospital (average of the period: 13.0 ± 2.5 days). Visceral fat area (VFA) was also assessed by dual impedance method. During hospitalization, there was a significant reduction in body weight, BMI, lean body mass, VFA and circulating DPP-4/sCD26 concentrations, but not in body fat mass. Fasting circulating DPP-4/sCD26 concentrations were significantly correlated with fasting insulin, aspartate aminotransferase, γ-glutamyltransferase (γ-GTP) levels, and HOMA-IR (r = 0.477, 0.423, 0.415, 0.548, respectively), but not with VFA (r = - 0.056) by liner regression analyses at base line. It was also observed a positive correlation between changes in circulating DPP-4/sCD26 concentrations and γ-GTP level, HOMA-IR, and a negative correlation between the changes in circulating DPP-4/sCD26 concentrations and VFA significantly (r = 0.300, 0.633, - 0.343, respectively). In conclusion, our observations suggest that liver enzymes as well as VFA might be associated with the response of DPP-4/sCD26 concentrations.
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Petito G, Cioffi F, Silvestri E, De Matteis R, Lattanzi D, de Lange P, Lombardi A, Moreno M, Goglia F, Lanni A, Senese R. 3,5-Diiodo-L-Thyronine (T2) Administration Affects Visceral Adipose Tissue Inflammatory State in Rats Receiving Long-Lasting High-Fat Diet. Front Endocrinol (Lausanne) 2021; 12:703170. [PMID: 34322094 PMCID: PMC8312549 DOI: 10.3389/fendo.2021.703170] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Accepted: 06/28/2021] [Indexed: 01/03/2023] Open
Abstract
3,5-diiodo-thyronine (T2), an endogenous metabolite of thyroid hormones, exerts beneficial metabolic effects. When administered to overweight rats receiving a high fat diet (HFD), it significantly reduces body fat accumulation, which is a risk factor for the development of an inflammatory state and of related metabolic diseases. In the present study, we focused our attention on T2 actions aimed at improving the adverse effects of long-lasting HFD such as the adipocyte inflammatory response. For this purpose, three groups of rats were used throughout: i) receiving a standard diet for 14 weeks; ii) receiving a HFD for 14 weeks, and iii) receiving a HFD for 14 weeks with a simultaneous daily injection of T2 for the last 4 weeks. The results showed that T2 administration ameliorated the expression profiles of pro- and anti-inflammatory cytokines, reduced macrophage infiltration in white adipose tissue, influenced their polarization and reduced lymphocytes recruitment. Moreover, T2 improved the expression of hypoxia markers, all altered in HFD rats, and reduced angiogenesis by decreasing the pro-angiogenic miR126 expression. Additionally, T2 reduced the oxidative damage of DNA, known to be associated to the inflammatory status. This study demonstrates that T2 is able to counteract some adverse effects caused by a long-lasting HFD and to produce beneficial effects on inflammation. Irisin and SIRT1 pathway may represent a mechanism underlying the above described effects.
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Affiliation(s)
- Giuseppe Petito
- Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania “L. Vanvitelli”, Caserta, Italy
| | - Federica Cioffi
- Department of Sciences and Technologies, University of Sannio, Benevento, Italy
- *Correspondence: Rosalba Senese, ; Federica Cioffi,
| | - Elena Silvestri
- Department of Sciences and Technologies, University of Sannio, Benevento, Italy
| | - Rita De Matteis
- Department of Biomolecular Sciences, Urbino University, Urbino, Italy
| | - Davide Lattanzi
- Department of Biomolecular Sciences, Urbino University, Urbino, Italy
| | - Pieter de Lange
- Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania “L. Vanvitelli”, Caserta, Italy
| | - Assunta Lombardi
- Department of Biology, University of Naples Federico II, Naples, Italy
| | - Maria Moreno
- Department of Sciences and Technologies, University of Sannio, Benevento, Italy
| | - Fernando Goglia
- Department of Sciences and Technologies, University of Sannio, Benevento, Italy
| | - Antonia Lanni
- Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania “L. Vanvitelli”, Caserta, Italy
| | - Rosalba Senese
- Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania “L. Vanvitelli”, Caserta, Italy
- *Correspondence: Rosalba Senese, ; Federica Cioffi,
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Gutaj P, Sibiak R, Jankowski M, Awdi K, Bryl R, Mozdziak P, Kempisty B, Wender-Ozegowska E. The Role of the Adipokines in the Most Common Gestational Complications. Int J Mol Sci 2020; 21:ijms21249408. [PMID: 33321877 PMCID: PMC7762997 DOI: 10.3390/ijms21249408] [Citation(s) in RCA: 44] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2020] [Revised: 12/03/2020] [Accepted: 12/08/2020] [Indexed: 12/12/2022] Open
Abstract
Adipocytokines are hormonally active molecules that are believed to play a key role in the regulation of crucial biological processes in the human body. Numerous experimental studies established significant alterations in the adipokine secretion patterns throughout pregnancy. The exact etiology of various gestational complications, such as gestational diabetes, preeclampsia, and fetal growth abnormalities, needs to be fully elucidated. The discovery of adipokines raised questions about their potential contribution to the molecular pathophysiology of those diseases. Multiple studies analyzed their local mRNA expression and circulating protein levels. However, most studies report conflicting results. Several adipokines such as leptin, resistin, irisin, apelin, chemerin, and omentin were proposed as potential novel early markers of heterogeneous gestational complications. The inclusion of the adipokines in the standard predictive multifactorial models could improve their prognostic values. Nonetheless, their independent diagnostic value is mostly insufficient to be implemented into standard clinical practice. Routine assessments of adipokine levels during pregnancy are not recommended in the management of both normal and complicated pregnancies. Based on the animal models (e.g., apelin and its receptors in the rodent preeclampsia models), future implementation of adipokines and their receptors as new therapeutic targets appears promising but requires further validation in humans.
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Affiliation(s)
- Paweł Gutaj
- Department of Reproduction, Chair of Obstetrics, Gynecology, and Gynecologic Oncology, Poznań University of Medical Sciences, 60-535 Poznan, Poland; (R.S.); (E.W.-O.)
- Correspondence: ; Tel.: +61-854-65-55
| | - Rafał Sibiak
- Department of Reproduction, Chair of Obstetrics, Gynecology, and Gynecologic Oncology, Poznań University of Medical Sciences, 60-535 Poznan, Poland; (R.S.); (E.W.-O.)
- Department of Histology and Embryology, Poznań University of Medical Sciences, 60-781 Poznan, Poland;
| | - Maurycy Jankowski
- Department of Anatomy, Poznań University of Medical Sciences, 60-781 Poznan, Poland; (M.J.); (R.B.)
| | - Karina Awdi
- Student’s Scientific Society, Poznan University of Medical Sciences, 60-806 Poznan, Poland;
| | - Rut Bryl
- Department of Anatomy, Poznań University of Medical Sciences, 60-781 Poznan, Poland; (M.J.); (R.B.)
| | - Paul Mozdziak
- Physiology Graduate Program, North Carolina State University, Raleigh, NC 27695-7608, USA;
| | - Bartosz Kempisty
- Department of Histology and Embryology, Poznań University of Medical Sciences, 60-781 Poznan, Poland;
- Department of Anatomy, Poznań University of Medical Sciences, 60-781 Poznan, Poland; (M.J.); (R.B.)
- Department of Obstetrics and Gynecology, University Hospital, Masaryk University, 625 00 Brno, Czech Republic
- Department of Veterinary Surgery, Institute of Veterinary Medicine, Nicolaus Copernicus University in Toruń, 87-100 Torun, Poland
| | - Ewa Wender-Ozegowska
- Department of Reproduction, Chair of Obstetrics, Gynecology, and Gynecologic Oncology, Poznań University of Medical Sciences, 60-535 Poznan, Poland; (R.S.); (E.W.-O.)
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29
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Sajja A, Abdelrahman KM, Reddy AS, Dey AK, Uceda DE, Lateef SS, Sorokin AV, Teague HL, Chung J, Rivers J, Joshi AA, Elnabawi YA, Goyal A, Rodante JA, Keel A, Alvarez JE, Lockshin B, Prussick R, Siegel E, Playford MP, Chen MY, Bluemke DA, Gelfand JM, Mehta NN. Chronic inflammation in psoriasis promotes visceral adiposity associated with noncalcified coronary burden over time. JCI Insight 2020; 5:142534. [PMID: 33104056 PMCID: PMC7710282 DOI: 10.1172/jci.insight.142534] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2020] [Accepted: 10/07/2020] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Psoriasis is a chronic inflammatory skin disease associated with increased obesity, noncalcified coronary artery burden (NCB), and incident myocardial infarction. Here, we sought to assess the relationship among inflammation, visceral adipose tissue (VAT), and NCB. Furthermore, we evaluated whether improvement in VAT would be associated with reduction in NCB over time in psoriasis. METHODS Consecutive psoriasis patients underwent coronary CT angiography to quantify NCB and abdominal CT to calculate VAT at baseline (n = 237), 1 year (n = 176), and 4 years (n = 50). RESULTS Patients with high levels of high-sensitivity C-reactive protein (hs-CRP) had significantly greater visceral adiposity (17,952.9 ± 849.2 cc3 vs. 13370.7 ± 806.8 cc3, P < 0.001) and noncalcified coronary burden (1.26 ± 0.03 vs. 1.07 ± 0.02 mm2) than those with low levels of hs-CRP. Those with higher levels of VAT had more systemic inflammation (hs-CRP, median [IQR], 2.5 mg/L [1.0–5.3 mg/L] vs. 1.2 mg/L [0.6–2.9 mg/L]), with approximately 50% higher NCB (1.42 ± 0.6 mm2 vs. 0.91 ± 0.2 mm2, P < 0.001). VAT associated with NCB in fully adjusted models (β = 0.47, P < 0.001). At 1-year follow-up, patients who had worsening hs-CRP had an increase in VAT (14,748.7 ± 878.1 cc3 to 15,158.7 ± 881.5 cc3; P = 0.03), whereas those who had improved hs-CRP improved their VAT (16,876.1 ± 915.2 cc3 to 16310.4 ± 889.6 cc3; P = 0.04). At 1 year, there was 10.3% reduction in NCB in those who had decreased VAT (β = 0.26, P < 0.0001), which persisted in a subset of patients at 4 years (β = 0.39, P = 0.003). CONCLUSIONS Inflammation drives development of VAT, increased cardiometabolic risk, and NCB in psoriasis. Reduction of inflammation associated with reduction in VAT and associated with longitudinal improvement in NCB. These findings demonstrate the important role of inflammation in the development of VAT in humans and its effect on early atherogenesis. TRIAL REGISTRATION ClinicalTrials.gov NCT01778569. FUNDING This study was supported by the National Heart, Lung, and Blood Institute Intramural Research Program (HL006193-05), the NIH Medical Research Scholars Program, a public-private partnership supported jointly by the NIH and contributions to the Foundation for the NIH from the Doris Duke Charitable Foundation (no. 2014194), the American Association for Dental Research, the Colgate-Palmolive Company, Genentech, and Elsevier as well as private donors. Inflammation is associated with development of visceral adiposity and coronary artery disease in humans.
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Affiliation(s)
- Aparna Sajja
- Johns Hopkins Hospital, Baltimore, Maryland, USA
| | | | - Aarthi S Reddy
- National Heart, Lung, and Blood Institute, Bethesda, Maryland, USA
| | - Amit K Dey
- National Heart, Lung, and Blood Institute, Bethesda, Maryland, USA
| | - Domingo E Uceda
- National Heart, Lung, and Blood Institute, Bethesda, Maryland, USA
| | - Sundus S Lateef
- National Heart, Lung, and Blood Institute, Bethesda, Maryland, USA
| | | | - Heather L Teague
- National Heart, Lung, and Blood Institute, Bethesda, Maryland, USA
| | - Jonathan Chung
- National Heart, Lung, and Blood Institute, Bethesda, Maryland, USA
| | - Joshua Rivers
- National Heart, Lung, and Blood Institute, Bethesda, Maryland, USA
| | - Aditya A Joshi
- National Heart, Lung, and Blood Institute, Bethesda, Maryland, USA
| | | | | | - Justin A Rodante
- National Heart, Lung, and Blood Institute, Bethesda, Maryland, USA
| | - Andrew Keel
- National Heart, Lung, and Blood Institute, Bethesda, Maryland, USA
| | - Julie E Alvarez
- National Heart, Lung, and Blood Institute, Bethesda, Maryland, USA
| | | | - Ronald Prussick
- Washington Dermatology Center, Rockville, Maryland, USA; George Washington University, Washington, DC, USA
| | - Evan Siegel
- Arthritis and Rheumatism Associates, Rockville, Maryland, USA
| | | | - Marcus Y Chen
- National Heart, Lung, and Blood Institute, Bethesda, Maryland, USA
| | - David A Bluemke
- University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA
| | - Joel M Gelfand
- University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Nehal N Mehta
- National Heart, Lung, and Blood Institute, Bethesda, Maryland, USA
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Verma N, Thakkar N, Phillips J, Ealey K, Sung HK. Dynamic remodeling of white adipose tissue by intermittent fasting. Curr Opin Food Sci 2020. [DOI: 10.1016/j.cofs.2020.10.023] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Role of c-Jun N-terminal Kinase (JNK) in Obesity and Type 2 Diabetes. Cells 2020; 9:cells9030706. [PMID: 32183037 PMCID: PMC7140703 DOI: 10.3390/cells9030706] [Citation(s) in RCA: 145] [Impact Index Per Article: 29.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2019] [Revised: 02/16/2020] [Accepted: 03/11/2020] [Indexed: 12/13/2022] Open
Abstract
Obesity has been described as a global epidemic and is a low-grade chronic inflammatory disease that arises as a consequence of energy imbalance. Obesity increases the risk of type 2 diabetes (T2D), by mechanisms that are not entirely clarified. Elevated circulating pro-inflammatory cytokines and free fatty acids (FFA) during obesity cause insulin resistance and ß-cell dysfunction, the two main features of T2D, which are both aggravated with the progressive development of hyperglycemia. The inflammatory kinase c-jun N-terminal kinase (JNK) responds to various cellular stress signals activated by cytokines, free fatty acids and hyperglycemia, and is a key mediator in the transition between obesity and T2D. Specifically, JNK mediates both insulin resistance and ß-cell dysfunction, and is therefore a potential target for T2D therapy.
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32
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Neeland IJ, Boone SC, Mook‐Kanamori DO, Ayers C, Smit RAJ, Tzoulaki I, Karaman I, Boulange C, Vaidya D, Punjabi N, Allison M, Herrington DM, Jukema JW, Rosendaal FR, Lamb HJ, van Dijk KW, Greenland P, de Mutsert R. Metabolomics Profiling of Visceral Adipose Tissue: Results From MESA and the NEO Study. J Am Heart Assoc 2019; 8:e010810. [PMID: 31017036 PMCID: PMC6512086 DOI: 10.1161/jaha.118.010810] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2018] [Accepted: 02/19/2019] [Indexed: 12/22/2022]
Abstract
Background Identifying associations between serum metabolites and visceral adipose tissue ( VAT ) could provide novel biomarkers of VAT and insights into the pathogenesis of obesity-related diseases. We aimed to discover and replicate metabolites reflecting pathways related to VAT . Methods and Results Associations between fasting serum metabolites and VAT area (by computed tomography or magnetic resonance imaging) were assessed with cross-sectional linear regression of individual-level data from participants in MESA (Multi-Ethnic Study of Atherosclerosis; discovery, N=1103) and the NEO (Netherlands Epidemiology of Obesity) study (replication, N=2537). Untargeted 1H nuclear magnetic resonance metabolomics profiling of serum was performed in MESA, and metabolites were replicated in the NEO study using targeted 1H nuclear magnetic resonance spectroscopy. A total of 30 590 metabolomic spectral variables were evaluated. After adjustment for age, sex, race/ethnicity, socioeconomic status, smoking, physical activity, glucose/lipid-lowering medication, and body mass index, 2104 variables representing 24 nonlipid and 49 lipid/lipoprotein subclass metabolites remained significantly associated with VAT ( P=4.88×10-20-1.16×10-3). These included conventional metabolites, amino acids, acetylglycoproteins, intermediates of glucose and hepatic metabolism, organic acids, and subclasses of apolipoproteins, cholesterol, phospholipids, and triglycerides. Metabolites mapped to 31 biochemical pathways, including amino acid substrate use/metabolism and glycolysis/gluconeogenesis. In the replication cohort, acetylglycoproteins, branched-chain amino acids, lactate, glutamine (inversely), and atherogenic lipids remained associated with VAT ( P=1.90×10-35-8.46×10-7), with most associations remaining after additional adjustment for surrogates of VAT (glucose level, waist circumference, and serum triglycerides), reflecting novel independent associations. Conclusions We identified and replicated a metabolite panel associated with VAT in 2 community-based cohorts. These findings persisted after adjustment for body mass index and appear to define a metabolic signature of visceral adiposity.
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Affiliation(s)
- Ian J. Neeland
- Division of CardiologyDepartment of Internal MedicineUniversity of Texas Southwestern Medical CenterDallasTX
| | - Sebastiaan C. Boone
- Department of Clinical EpidemiologyLeiden University Medical CenterLeidenthe Netherlands
| | - Dennis O. Mook‐Kanamori
- Department of Clinical EpidemiologyLeiden University Medical CenterLeidenthe Netherlands
- Department of Public Health and Primary CareLeiden University Medical CenterLeidenthe Netherlands
| | - Colby Ayers
- Department of Clinical SciencesUniversity of Texas Southwestern Medical CenterDallasTX
| | - Roelof A. J. Smit
- Department of Clinical EpidemiologyLeiden University Medical CenterLeidenthe Netherlands
| | - Ioanna Tzoulaki
- Department of Epidemiology and BiostatisticsImperial College LondonLondonUnited Kingdom
| | - Ibrahim Karaman
- Department of Epidemiology and BiostatisticsImperial College LondonLondonUnited Kingdom
| | | | | | - Naresh Punjabi
- Department of MedicineJohns Hopkins UniversityBaltimoreMD
| | - Matthew Allison
- Department of Family Medicine and Public HealthUniversity of California San DiegoLa JollaCA
| | | | - J. Wouter Jukema
- Department of CardiologyLeiden University Medical CenterLeidenthe Netherlands
| | - Frits R. Rosendaal
- Department of Clinical EpidemiologyLeiden University Medical CenterLeidenthe Netherlands
| | - Hildo J. Lamb
- Department of RadiologyLeiden University Medical CenterLeidenthe Netherlands
| | - Ko Willems van Dijk
- Department of Human GeneticsLeiden University Medical CenterLeidenthe Netherlands
- Department of Internal MedicineLeiden University Medical CenterLeidenthe Netherlands
- Einthoven Laboratory for Experimental Vascular MedicineLeiden University Medical CenterLeidenthe Netherlands
| | - Philip Greenland
- Department of Preventive MedicineNorthwestern UniversityChicagoIL
| | - Renée de Mutsert
- Department of Clinical EpidemiologyLeiden University Medical CenterLeidenthe Netherlands
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Aryl hydrocarbon receptor agonist indigo protects against obesity-related insulin resistance through modulation of intestinal and metabolic tissue immunity. Int J Obes (Lond) 2019; 43:2407-2421. [PMID: 30944419 PMCID: PMC6892742 DOI: 10.1038/s41366-019-0340-1] [Citation(s) in RCA: 50] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2018] [Revised: 12/24/2018] [Accepted: 02/19/2019] [Indexed: 02/08/2023]
Abstract
Background/objectives Low-grade chronic inflammation in visceral adipose tissue and the intestines are important drivers of obesity associated insulin resistance. Bioactive compounds derived from plants are an important source of potential novel therapies for the treatment of chronic diseases. In search for new immune based treatments of obesity associated insulin resistance, we screened for tissue relevant anti-inflammatory properties in 20 plant-based extracts. Methods We screened 20 plant-based extracts to assess for preferential production of IL-10 compared to TNFα, specifically targetting metabolic tissues, including the visceral adipose tissue. We assessed the therapeutic potential of the strongest anti-inflammatory compound, indigo, in the C57BL/6J diet-induced obesity mouse model with supplementation for up to 16 weeks by measuring changes in body weight, glucose and insulin tolerance, and gut barrier function. We also utilized flow cytometry, quantitative PCR, enzyme-linked immunosorbent assay (ELISA), and histology to measure changes to immune cells populations and cytokine profiles in the intestine, visceral adipose tissue (VAT), and liver. 16SrRNA sequencing was performed to examine gut microbial differences induced by indigo supplementation. Results We identifed indigo, an aryl hydrocarbon receptor (AhR) ligand agonist, as a potent inducer of IL-10 and IL-22, which protects against high-fat diet (HFD)-induced insulin resistance and fatty liver disease in the diet-induced obesity model. Therapeutic actions were mechanistically linked to decreased inflammatory immune cell tone in the intestine, VAT and liver. Specifically, indigo increased Lactobacillus bacteria and elicited IL-22 production in the gut, which improved intestinal barrier permeability and reduced endotoxemia. These changes were associated with increased IL-10 production by immune cells residing in liver and VAT. Conclusions Indigo is a naturally occurring AhR ligand with anti-inflammatory properties that effectively protects against HFD-induced glucose dysregulation. Compounds derived from indigo or those with similar properties could represent novel therapies for diseases associated with obesity-related metabolic tissue inflammation.
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Obesity-Induced TNFα and IL-6 Signaling: The Missing Link between Obesity and Inflammation-Driven Liver and Colorectal Cancers. Cancers (Basel) 2018; 11:cancers11010024. [PMID: 30591653 PMCID: PMC6356226 DOI: 10.3390/cancers11010024] [Citation(s) in RCA: 158] [Impact Index Per Article: 22.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2018] [Revised: 12/20/2018] [Accepted: 12/21/2018] [Indexed: 02/06/2023] Open
Abstract
Obesity promotes the development of numerous cancers, such as liver and colorectal cancers, which is at least partly due to obesity-induced, chronic, low-grade inflammation. In particular, the recruitment and activation of immune cell subsets in the white adipose tissue systemically increase proinflammatory cytokines, such as tumor necrosis factor α (TNFα) and interleukin-6 (IL-6). These proinflammatory cytokines not only impair insulin action in metabolic tissues, but also favor cancer development. Here, we review the current state of knowledge on how obesity affects inflammatory TNFα and IL-6 signaling in hepatocellular carcinoma and colorectal cancers.
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Miranda ER, Fuller KNZ, Perkins RK, Kroeger CM, Trepanowski JF, Varady KA, Haus JM. Endogenous secretory RAGE increases with improvements in body composition and is associated with markers of adipocyte health. Nutr Metab Cardiovasc Dis 2018; 28:1155-1165. [PMID: 30297199 PMCID: PMC6231965 DOI: 10.1016/j.numecd.2018.07.009] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2018] [Revised: 07/23/2018] [Accepted: 07/24/2018] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIMS The receptor for advanced glycation end products (RAGE) is implicated in obesogenesis. Conversely, soluble RAGE (sRAGE) competitively inhibits RAGE. Our aim was to determine the effects of weight-loss via alternate day fasting (ADF) on sRAGE isoforms and evaluate potential relationships with body composition. METHODS AND RESULTS 42 obese participants were randomized to control (CON) or ADF. For 24 weeks, the ADF group consumed 25% or 125% of their caloric requirements on alternating days while the CON group did not change their diet. Body fat was measured via DXA, visceral fat (VAT) via MRI and subcutaneous fat (SAT) was derived by subtracting VAT from total fat. sRAGE isoforms were measured via ELISAs. After 24 weeks, ADF -6.8 (-9.5, -3.5)kg (Median, IQR) lost more weight than CON -0.3 (-1.9, 1.0)kg (p < 0.05). The change in endogenous secretory RAGE (esRAGE) was different between ADF 15 (-30, 78)pg/mL and CON -21 (-72, 16)pg/mL after 24 weeks (p < 0.05). To examine the effect of changes in body composition, the cohort was stratified by median weight-, fat-, SAT-, and VAT-loss. The changes in all sRAGE isoforms were different between those above and below median weight-loss (p < 0.05) with sRAGE isoforms tending to decrease in individuals below the median. Changes in total sRAGE and esRAGE were different between individuals above compared to below median fat- and SAT-loss (p < 0.05). Those above median fat-loss increased esRAGE by 29 (-5, 66)pg/mL (p < 0.05). CONCLUSION Improvements in body composition are related to increased sRAGE isoforms, implicating sRAGE as a potential target for the treatment of obesity. CLINICAL TRIAL REGISTRATION NCT00960505.
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Affiliation(s)
- E R Miranda
- School of Kinesiology, University of Michigan, Ann Arbor, MI, United States
| | - K N Z Fuller
- Kinesiology and Nutrition, University of Illinois at Chicago, Chicago, IL, United States
| | - R K Perkins
- School of Kinesiology, University of Michigan, Ann Arbor, MI, United States
| | - C M Kroeger
- Department of Epidemiology and Biostatistics, Indiana University School of Public Health-Bloomington, Bloomington, IN, United States
| | - J F Trepanowski
- Kinesiology and Nutrition, University of Illinois at Chicago, Chicago, IL, United States
| | - K A Varady
- Kinesiology and Nutrition, University of Illinois at Chicago, Chicago, IL, United States
| | - J M Haus
- School of Kinesiology, University of Michigan, Ann Arbor, MI, United States.
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Abstract
Vitamin D, a secosteroid predominately obtained by endogenous production, has in recent years been linked to obesity and its comorbidities. The purpose of this review is to draw conclusions from animal and human studies on the effects of vitamin D on adipogenesis to identify the molecular links between vitamin D and obesity. The information presented herein was obtained from 4 databases (PubMed, CINAHL, Cochrane Library, Scopus) using predefined search terms, as well as research literature and other reviews. The effects of vitamin D on adipogenesis have been researched in several animal models, and the majority of these studies suggest vitamin D plays an inhibitory role in adipogenesis. Studies into vitamin D status and obesity in humans are limited, with the majority being observational epidemiological studies that provide no conclusions on cause and effect or clear links on the molecular mechanisms. The few cell culture and supplementation studies that have investigated adipogenesis in human cells indicate that, in contrast to findings from rodent studies, vitamin D is proadipogenic. There is insufficient evidence to determine whether 1) vitamin D deficiency is associated with a lean or obese phenotype, 2) vitamin D deficiency is a consequence of obesity, or (3) the effects of vitamin D on fat tissue are due to interactions with calcium.
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Affiliation(s)
- Clare F Dix
- Centre for Dietetic Research, School of Human Movement and Nutrition Sciences, University of Queensland, Brisbane, Australia
| | | | - Olivia R L Wright
- Centre for Dietetic Research, School of Human Movement and Nutrition Sciences, University of Queensland, Brisbane, Australia
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Borbély YM, Osterwalder A, Kröll D, Nett PC, Inglin RA. Diarrhea after bariatric procedures: Diagnosis and therapy. World J Gastroenterol 2017; 23:4689-4700. [PMID: 28765690 PMCID: PMC5514634 DOI: 10.3748/wjg.v23.i26.4689] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2016] [Revised: 03/30/2017] [Accepted: 06/19/2017] [Indexed: 02/07/2023] Open
Abstract
Diarrhea after bariatric procedures, mainly those with malabsorptive elements including Roux-Y Gastric Bypass and Biliopancreatic Diversion, is common and an essential determinant of quality of life and micro- and macronutrient deficiencies. Bariatric surgery is the only sustainably successful method to address morbid obesity and its comorbidities, particularly gaining more and more importance in the specific treatment of diabetic patients. Approximately half a million procedures are annually performed around the world, with numbers expected to rise drastically in the near future. A multitude of factors exert their influence on bowel habits; preoperative comorbidities and procedure-related aspects are intertwined with postoperative nutritional habits. Diagnosis may be challenging owing to the characteristics of post-bariatric surgery anatomy with hindered accessibility of excluded segments of the small bowel and restriction at the gastric level. Conventional testing measures, if available, generally yield low accuracy and are usually not validated in this specific population. Limited trials of empiric treatment are a practical alternative and oftentimes an indispensable part of the diagnostic process. This review provides an overview of causes for chronic post-bariatric surgery diarrhea and details the particularities of its diagnosis and treatment in this specific patient population. Topics of current interest such as the impact of gut microbiota and the influence of bile acids on morbid obesity and especially their role in diarrhea are highlighted in order to provide a better understanding of the specific problems and chances of future treatment in post-bariatric surgery patients.
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Poddar M, Chetty Y, Chetty VT. How does obesity affect the endocrine system? A narrative review. Clin Obes 2017; 7:136-144. [PMID: 28294570 DOI: 10.1111/cob.12184] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2016] [Revised: 11/29/2016] [Accepted: 12/08/2016] [Indexed: 01/18/2023]
Abstract
Obesity is a chronic, relapsing medical condition that results from an imbalance of energy expenditure and consumption. It is a leading cause of preventable illness, disability and premature death. The causes of obesity are multifactorial and include behavioural, socioeconomic, genetic, environmental and psychosocial factors. Rarely are endocrine diseases, e.g., hypothyroidism or Cushing's syndrome, the cause of obesity. What is less understood is how obesity affects the endocrine system. In this review, we will discuss the impact of obesity on multiple endocrine systems, including the hypothalamic-pituitary axis, changes in vitamin D homeostasis, gender steroids and thyroid hormones. We will also examine the renin angiotensin aldosterone system and insulin pathophysiology associated with obesity. We will provide a general overview of the biochemical changes that can be seen in patients with obesity, review possible aetiologies of these changes and briefly consider current guidelines on their management. This review will not discuss endocrine causes of obesity.
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Affiliation(s)
- M Poddar
- Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada
| | - Y Chetty
- University of Queensland, Brisbane, QLD, Australia
| | - V T Chetty
- Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada
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The Pathogenesis of Obesity-Associated Adipose Tissue Inflammation. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2017; 960:221-245. [PMID: 28585201 DOI: 10.1007/978-3-319-48382-5_9] [Citation(s) in RCA: 190] [Impact Index Per Article: 23.8] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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Morris JL, Bridson TL, Alim MA, Rush CM, Rudd DM, Govan BL, Ketheesan N. Development of a diet-induced murine model of diabetes featuring cardinal metabolic and pathophysiological abnormalities of type 2 diabetes. Biol Open 2016; 5:1149-62. [PMID: 27402965 PMCID: PMC5004603 DOI: 10.1242/bio.016790] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023] Open
Abstract
The persistent rise in global incidence of type 2 diabetes (T2D) continues to have significant public health and economic implications. The availability of relevant animal models of T2D is critical to elucidating the complexity of the pathogenic mechanisms underlying this disease and the implications this has on susceptibility to T2D complications. Whilst many high-fat diet-induced rodent models of obesity and diabetes exist, growing appreciation of the contribution of high glycaemic index diets on the development of hyperglycaemia and insulin resistance highlight the requirement for animal models that more closely represent global dietary patterns reflective of modern society. To that end, we sought to develop and validate a murine model of T2D based on consumption of an energy-dense diet containing moderate levels of fat and a high glycaemic index to better reflect the aetiopathogenesis of T2D. Male C57BL/6 mice were fed an energy-dense (ED) diet and the development of pathological features used in the clinical diagnosis of T2D was assessed over a 30-week period. Compared with control mice, 87% of mice fed an ED diet developed pathognomonic signs of T2D including glucose intolerance, hyperglycaemia, glycosylated haemoglobin (HbA1c) and glycosuria within 30 weeks. Furthermore, dyslipidaemia, chronic inflammation, alterations in circulating leucocytes and renal impairment were also evident in ED diet-fed mice compared with mice receiving standard rodent chow. Longitudinal profiling of metabolic and biochemical parameters provide support of an aetiologically and clinically relevant model of T2D that will serve as a valuable tool for mechanistic and therapeutic studies investigating the pathogenic complications of T2D.
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Affiliation(s)
- Jodie L Morris
- Australian Institute of Tropical Health and Medicine, Division of Tropical Health and Medicine, James Cook University, Townsville, Queensland 4811, Australia
| | - Tahnee L Bridson
- Australian Institute of Tropical Health and Medicine, Division of Tropical Health and Medicine, James Cook University, Townsville, Queensland 4811, Australia
| | - Md Abdul Alim
- Australian Institute of Tropical Health and Medicine, Division of Tropical Health and Medicine, James Cook University, Townsville, Queensland 4811, Australia
| | - Catherine M Rush
- Australian Institute of Tropical Health and Medicine, Division of Tropical Health and Medicine, James Cook University, Townsville, Queensland 4811, Australia
| | - Donna M Rudd
- Australian Institute of Tropical Health and Medicine, Division of Tropical Health and Medicine, James Cook University, Townsville, Queensland 4811, Australia
| | - Brenda L Govan
- Australian Institute of Tropical Health and Medicine, Division of Tropical Health and Medicine, James Cook University, Townsville, Queensland 4811, Australia
| | - Natkunam Ketheesan
- Australian Institute of Tropical Health and Medicine, Division of Tropical Health and Medicine, James Cook University, Townsville, Queensland 4811, Australia
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Hersoug LG, Møller P, Loft S. Gut microbiota-derived lipopolysaccharide uptake and trafficking to adipose tissue: implications for inflammation and obesity. Obes Rev 2016; 17:297-312. [PMID: 26712364 DOI: 10.1111/obr.12370] [Citation(s) in RCA: 203] [Impact Index Per Article: 22.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2015] [Revised: 11/18/2015] [Accepted: 11/19/2015] [Indexed: 12/12/2022]
Abstract
The composition of the gut microbiota and excessive ingestion of high-fat diets (HFD) are considered to be important factors for development of obesity. In this review we describe a coherent mechanism of action for the development of obesity, which involves the composition of gut microbiota, HFD, low-grade inflammation, expression of fat translocase and scavenger receptor CD36, and the scavenger receptor class B type 1 (SR-BI). SR-BI binds to both lipids and lipopolysaccharide (LPS) from Gram-negative bacteria, which may promote incorporation of LPS in chylomicrons (CMs). These CMs are transported via lymph to the circulation, where LPS is transferred to other lipoproteins by translocases, preferentially to HDL. LPS increases the SR-BI binding, transcytosis of lipoproteins over the endothelial barrier,and endocytosis in adipocytes. Especially large size adipocytes with high metabolic activity absorb LPS-rich lipoproteins. In addition, macrophages in adipose tissue internalize LPS-lipoproteins. This may contribute to the polarization from M2 to M1 phenotype, which is a consequence of increased LPS delivery into the tissue during hypertrophy. In conclusion, evidence suggests that LPS is involved in the development of obesity as a direct targeting molecule for lipid delivery and storage in adipose tissue.
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Affiliation(s)
- L-G Hersoug
- Section of Environmental Health, Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - P Møller
- Section of Environmental Health, Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - S Loft
- Section of Environmental Health, Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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Jung JG, Yang JN, Lee CG, Choi SH, Kwack WG, Lee JH, Kang HW. Visceral adiposity is associated with an increased risk of functional dyspepsia. J Gastroenterol Hepatol 2016; 31:567-74. [PMID: 26313910 DOI: 10.1111/jgh.13146] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2015] [Revised: 08/03/2015] [Accepted: 08/13/2015] [Indexed: 12/18/2022]
Abstract
BACKGROUND The relationship between visceral adiposity and the incidence of functional dyspepsia (FD) has not yet been studied. The purpose of the present study is to evaluate the association between visceral adiposity and the risk of FD. METHODS This is a case-control study that compares the abdominal adipose tissue area between subjects with FD and control subjects without FD, who underwent abdomen computerized tomography (CT) for health examinations in a tertiary center. Retrospectively, a telephone survey was conducted to diagnose FD using the Rome III criteria. We measured various indices of obesity including body mass index (BMI), waist circumference (WC), visceral adipose tissue (VAT) area, subcutaneous adipose tissue (SAT) area and the VAT/SAT ratio in order to evaluate the association between FD and abdominal adiposity. KEY RESULTS A total of 363 subjects were included in the present study. FD was diagnosed in 90 subjects (24.8%). In the univariate analysis, WC, VAT area, TAT area, VAT/SAT ratio, and the presence of erosive esophagitis were significantly higher in the FD group than in the non-FD group. In the multivariate analysis, a higher VAT area (odds ratio (OR), 3.76; 95% confidence interval (CI), 1.24-11.40; highest quartile vs lowest quartile, p = 0.019) and VAT/SAT ratio (OR, 2.35; 95% CI, 1.27-4.32; highest quartile vs lowest quartile, p = 0.006) were independently associated with a risk of FD. CONCLUSION AND INFERENCES Visceral adiposity as measured by the VAT area and VAT/SAT ratio is associated with an increased risk of FD.
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Affiliation(s)
- Jae Gu Jung
- Department of Internal Medicine, Dongguk University Ilsan Hospital, College of Medicine, Goyang, Republic of Korea.,Department of Internal Medicine, Incheon Sarang Hospital, Incheon, Republic of Korea
| | - Jae Nam Yang
- Department of Internal Medicine, Dongguk University Ilsan Hospital, College of Medicine, Goyang, Republic of Korea
| | - Chang Geun Lee
- Department of Internal Medicine, Dongguk University Ilsan Hospital, College of Medicine, Goyang, Republic of Korea
| | - Sung Hun Choi
- Department of Internal Medicine, Dongguk University Ilsan Hospital, College of Medicine, Goyang, Republic of Korea
| | - Won Gun Kwack
- Department of Internal Medicine, Dongguk University Ilsan Hospital, College of Medicine, Goyang, Republic of Korea
| | - Jin Ho Lee
- Department of Internal Medicine, Dongguk University Ilsan Hospital, College of Medicine, Goyang, Republic of Korea
| | - Hyoun Woo Kang
- Department of Internal Medicine, Dongguk University Ilsan Hospital, College of Medicine, Goyang, Republic of Korea
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Vehapoglu A, Turkmen S, Goknar N, Özer ÖF. Reduced antioxidant capacity and increased subclinical inflammation markers in prepubescent obese children and their relationship with nutritional markers and metabolic parameters. Redox Rep 2016; 21:271-80. [PMID: 26865084 DOI: 10.1080/13510002.2015.1133035] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
OBJECTIVE There are associations between some inflammatory and oxidative markers and obesity in adults, but whether prepubescent children of different weights also have such markers has not been studied. We investigated multiple inflammatory markers and levels of erythrocyte oxidant/antioxidant enzymes in prepubescent children of different weights. METHODS Children aged 2-11 years were divided into three groups: 80 were underweight, 90 were obese but otherwise healthy, and 80 were healthy age- and sex-matched children of normal-weight. We analyzed inflammatory markers and the total oxidant status, total antioxidant status (TAS), and total thiol level were also determined, and the oxidative stress index was calculated as an indicator of the degree of oxidative stress. RESULTS The obese group exhibited higher levels of fasting glucose, insulin, total cholesterol, triglycerides, the homeostatic model assessment of insulin resistance (HOMA-IR), and the homeostatic model assessment of β-cell function (HOMA-β), C-reactive protein (CRP), neutrophils, and neutrophil/lymphocyte ratio (NLR), as well as lower TAS and total thiol levels than the other two groups (all P < 0.001). Moreover, TAS and total thiols were negatively correlated with age in the obese group (r = -0.212, P = 0.001; r = -0.231, P < 0.001, respectively). CRP levels in plasma were positively correlated with the body mass index (BMI), insulin and glucose levels, HOMA-IR, HOMA-β, WBC and neutrophil counts, and the NLR, and were negatively correlated with TAS and total thiol levels in the overall studied population. DISCUSSION The coexistence of increased obesity-related subclinical inflammation and decreased antioxidant capacity can be observed even in prepubescence, and may eventually increase the risk of long-term vascular damage.
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Affiliation(s)
- Aysel Vehapoglu
- a Department of Pediatrics, Faculty of Medicine , Bezmialem Vakıf University , Istanbul , Turkey
| | - Serdar Turkmen
- b Department of Biochemistry , Gaziosmanpaşa Taksim Training and Research Hospital , Istanbul , Turkey
| | - Nilufer Goknar
- a Department of Pediatrics, Faculty of Medicine , Bezmialem Vakıf University , Istanbul , Turkey
| | - Ömer Faruk Özer
- c Department of Biochemistry, School of Medicine , Bezmialem Vakıf University , Istanbul , Turkey
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Majdoubi A, Kishta OA, Thibodeau J. Role of antigen presentation in the production of pro-inflammatory cytokines in obese adipose tissue. Cytokine 2016; 82:112-21. [PMID: 26854212 DOI: 10.1016/j.cyto.2016.01.023] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2015] [Revised: 01/27/2016] [Accepted: 01/27/2016] [Indexed: 02/06/2023]
Abstract
Type II diabetes regroups different physiological anomalies that ultimately lead to low-grade chronic inflammation, insulin resistance and loss of pancreatic β-cells. Obesity is one of the best examples of such a condition that can develop into Metabolic Syndrome, causing serious health problems of great socio-economic consequences. The pathological outcome of obesity has a genetic basis and depends on the delicate balance between pro- and anti-inflammatory effectors of the immune system. The causal link between obesity and inflammation is well established. While innate immunity plays a key role in the development of a pro-inflammatory state in obese adipose tissues, it has now become clear that adaptive immune cells are also involved and participate in the cascade of events that lead to metabolic perturbations. The efficacy of some immunotherapeutic protocols in reducing the symptoms of obesity-driven metabolic syndrome in mice implicated all arms of the immune response. Recently, the production of pathogenic immunoglobulins and pro-inflammatory cytokines by B and T lymphocytes suggested an auto-immune basis for the establishment of a non-healthy obese state. Understanding the cellular landscape of obese adipose tissues and how immune cells sustain chronic inflammation holds the key to the development of targeted therapies. In this review, we emphasize the role of antigen-presenting cells and MHC molecules in obese adipose tissue and the general contribution of the adaptive arm of the immune system in inflammation-induced insulin resistance.
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Affiliation(s)
- Abdelilah Majdoubi
- Laboratoire d'Immunologie Moléculaire, Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Québec, Canada
| | - Osama A Kishta
- Laboratoire d'Immunologie Moléculaire, Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Québec, Canada
| | - Jacques Thibodeau
- Laboratoire d'Immunologie Moléculaire, Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Québec, Canada.
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Perriotte-Olson C, Adi N, Manickam DS, Westwood RA, Desouza CV, Natarajan G, Crook A, Kabanov AV, Saraswathi V. Nanoformulated copper/zinc superoxide dismutase reduces adipose inflammation in obesity. Obesity (Silver Spring) 2016; 24:148-56. [PMID: 26612356 PMCID: PMC6699510 DOI: 10.1002/oby.21348] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2015] [Revised: 08/20/2015] [Accepted: 08/26/2015] [Indexed: 12/17/2022]
Abstract
OBJECTIVE An intimate association exists between oxidative stress and inflammation. Because adipose tissue (AT) inflammation is intricately linked to metabolic disorders, it was hypothesized that reducing oxidative stress would be effective in ameliorating AT inflammation in obesity. METHODS Wild-type mice were fed a high-fat diet (HF) for 8 weeks followed by a 2-week treatment with nanoformulated copper/zinc superoxide dismutase (NanoSOD). The mice were divided into: 1) chow diet, 2) HF, and 3) HF + NanoSOD. RESULTS The HF + NanoSOD-treated mice showed a significant decrease in plasma and liver triglycerides when compared with HF-fed mice. Interestingly, NanoSOD reduced the expression of macrophage and inflammatory markers in visceral AT (VAT) and stromal cells derived from VAT. Moreover, the activation of proinflammatory signaling pathways, in particular, the extracellular signal-regulated kinases, was blunted in VAT on NanoSOD treatment. However, markers of oxidative stress were not altered significantly in the HF + NanoSOD group in the experimental conditions. Pretreatment of either macrophages or adipocytes significantly reduced the inflammatory response invoked in an in vitro coculture system, further supporting the role of NanoSOD in inhibiting obesity-linked inflammation. CONCLUSIONS This data suggest that NanoSOD is effective not only in reducing AT macrophage accumulation and AT inflammation but also in promoting triglyceride metabolism in obesity.
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Affiliation(s)
- Curtis Perriotte-Olson
- Department of Internal Medicine/Division of Diabetes, Endocrinology, and Metabolism, University of Nebraska Medical Center, Omaha, Nebraska, USA
- Research Service, Veterans Administration Nebraska-Western Iowa Health Care System, Omaha, Nebraska, USA
| | - Nikhil Adi
- Department of Internal Medicine/Division of Diabetes, Endocrinology, and Metabolism, University of Nebraska Medical Center, Omaha, Nebraska, USA
- Research Service, Veterans Administration Nebraska-Western Iowa Health Care System, Omaha, Nebraska, USA
| | - Devika S Manickam
- Division of Molecular Pharmaceutics and Center for Nanotechnology in Drug Delivery, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Rachel A Westwood
- Department of Internal Medicine/Division of Diabetes, Endocrinology, and Metabolism, University of Nebraska Medical Center, Omaha, Nebraska, USA
- Research Service, Veterans Administration Nebraska-Western Iowa Health Care System, Omaha, Nebraska, USA
| | - Cyrus V Desouza
- Department of Internal Medicine/Division of Diabetes, Endocrinology, and Metabolism, University of Nebraska Medical Center, Omaha, Nebraska, USA
- Research Service, Veterans Administration Nebraska-Western Iowa Health Care System, Omaha, Nebraska, USA
| | - Gopalakrishnan Natarajan
- Department of Internal Medicine/Division of Diabetes, Endocrinology, and Metabolism, University of Nebraska Medical Center, Omaha, Nebraska, USA
- Research Service, Veterans Administration Nebraska-Western Iowa Health Care System, Omaha, Nebraska, USA
| | - Alexandra Crook
- Department of Internal Medicine/Division of Diabetes, Endocrinology, and Metabolism, University of Nebraska Medical Center, Omaha, Nebraska, USA
- Research Service, Veterans Administration Nebraska-Western Iowa Health Care System, Omaha, Nebraska, USA
| | - Alexander V Kabanov
- Division of Molecular Pharmaceutics and Center for Nanotechnology in Drug Delivery, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Viswanathan Saraswathi
- Department of Internal Medicine/Division of Diabetes, Endocrinology, and Metabolism, University of Nebraska Medical Center, Omaha, Nebraska, USA
- Research Service, Veterans Administration Nebraska-Western Iowa Health Care System, Omaha, Nebraska, USA
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The Pattern of Adipose Tissue Accumulation during Early Infancy Provides an Environment for the Development of Dengue Hemorrhagic Fever. PLoS Negl Trop Dis 2015; 9:e0004267. [PMID: 26636570 PMCID: PMC4670217 DOI: 10.1371/journal.pntd.0004267] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2015] [Accepted: 11/05/2015] [Indexed: 02/04/2023] Open
Abstract
Background Dengue is the most prevalent arthropod-borne viral illness in humans with half of the world’s population at risk. During early infancy, severe dengue can develop after a primary dengue virus infection. There has been a clinical observation that severe dengue during the first year of life is seen only in chubby infants. Methodology/Principal Findings We examined the associations between the development of severe dengue and adipose tissue accumulation patterns during the first year of life in a prospective observational clinical study of infants and dengue virus infections. We found that adipose tissue contains two potential targets for dengue virus infection and production- adipocytes and adipose tissue macrophages. During the first year of life, total body adiposity and visceral adipose tissue stores were at their highest levels in early infancy. Early infancy was also characterized by a relative decrease in alternatively activated (anti-inflammatory) macrophages, and a relative increase in circulating pro-inflammatory cytokines. Conclusions/Significance The data has been used to propose a model where the adipose tissue accumulation pattern and pro-inflammatory environment during early infancy provide the conditions for the potential development of severe dengue in immune-susceptible infants. Dengue is the most prevalent arthropod-borne viral illness in humans with half of the world’s population at risk. During early infancy, severe dengue can develop after a primary dengue virus infection. There has been a clinical observation that severe dengue during the first year of life is seen only in chubby infants. We therefore examined the associations between the development of severe dengue and adipose tissue accumulation patterns during the first year of life in a prospective observational clinical study of infants and dengue virus infections. We found that adipose tissue contains two potential targets for dengue virus infection and production- adipocytes and adipose tissue macrophages. During the first year of life, total body adiposity and visceral adipose tissue stores were at their highest levels in early infancy. Early infancy was also characterized by a relative decrease in alternatively activated (anti-inflammatory) macrophages, and a relative increase in circulating pro-inflammatory cytokines. The accumulation of visceral adipose tissue, the relative decrease in alternatively activated macrophages, and the relative increase in circulating pro-inflammatory cytokines during early infancy provide the environment for the development of severe dengue in immune-susceptible infants.
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Arriarán S, Agnelli S, Remesar X, Fernández-López JA, Alemany M. Effects of sex and site on amino acid metabolism enzyme gene expression and activity in rat white adipose tissue. PeerJ 2015; 3:e1399. [PMID: 26587356 PMCID: PMC4647552 DOI: 10.7717/peerj.1399] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2015] [Accepted: 10/21/2015] [Indexed: 11/20/2022] Open
Abstract
Background and Objectives. White adipose tissue (WAT) shows marked sex- and diet-dependent differences. However, our metabolic knowledge of WAT, especially on amino acid metabolism, is considerably limited. In the present study, we compared the influence of sex on the amino acid metabolism profile of the four main WAT sites, focused on the paths related to ammonium handling and the urea cycle, as a way to estimate the extent of WAT implication on body amino-nitrogen metabolism. Experimental Design. Adult female and male rats were maintained, undisturbed, under standard conditions for one month. After killing them under isoflurane anesthesia. WAT sites were dissected and weighed. Subcutaneous, perigonadal, retroperitoneal and mesenteric WAT were analyzed for amino acid metabolism gene expression and enzyme activities. Results. There was a considerable stability of the urea cycle activities and expressions, irrespective of sex, and with only limited influence of site. Urea cycle was more resilient to change than other site-specialized metabolic pathways. The control of WAT urea cycle was probably related to the provision of arginine/citrulline, as deduced from the enzyme activity profiles. These data support a generalized role of WAT in overall amino-N handling. In contrast, sex markedly affected WAT ammonium-centered amino acid metabolism in a site-related way, with relatively higher emphasis in males' subcutaneous WAT. Conclusions. We found that WAT has an active amino acid metabolism. Its gene expressions were lower than those of glucose-lipid interactions, but the differences were quantitatively less important than usually reported. The effects of sex on urea cycle enzymes expression and activity were limited, in contrast with the wider variations observed in other metabolic pathways. The results agree with a centralized control of urea cycle operation affecting the adipose organ as a whole.
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Affiliation(s)
- Sofía Arriarán
- Department of Nutrition & Food Science, University of Barcelona, Faculty of Biology , Barcelona , Spain
| | - Silvia Agnelli
- Department of Nutrition & Food Science, University of Barcelona, Faculty of Biology , Barcelona , Spain
| | - Xavier Remesar
- Department of Nutrition & Food Science, University of Barcelona, Faculty of Biology , Barcelona , Spain ; Institute of Biomedicine, University of Barcelona , Barcelona , Spain ; CIBER OBN , Barcelona , Spain
| | - José Antonio Fernández-López
- Department of Nutrition & Food Science, University of Barcelona, Faculty of Biology , Barcelona , Spain ; Institute of Biomedicine, University of Barcelona , Barcelona , Spain ; CIBER OBN , Barcelona , Spain
| | - Marià Alemany
- Department of Nutrition & Food Science, University of Barcelona, Faculty of Biology , Barcelona , Spain ; Institute of Biomedicine, University of Barcelona , Barcelona , Spain ; CIBER OBN , Barcelona , Spain
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Wang X, He G, Peng Y, Zhong W, Wang Y, Zhang B. Sodium butyrate alleviates adipocyte inflammation by inhibiting NLRP3 pathway. Sci Rep 2015; 5:12676. [PMID: 26234821 PMCID: PMC4522654 DOI: 10.1038/srep12676] [Citation(s) in RCA: 88] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2015] [Accepted: 07/06/2015] [Indexed: 02/06/2023] Open
Abstract
Insulin resistance (IR) is a common feature of Type II diabetes, metabolic disorders, hypertension and other vascular diseases. Recent studies showed that obesity-induced inflammation may be critical for IR. To investigate the anti-inflammatory effect of sodium butyrate (NaB) on obesity-induced inflammation, the db/db mice were intraperitoneally injected with NaB for 6 weeks. Glucose control was evaluated by glucose tolerance test (GTT) and insulin tolerance test (ITT). Adipose tissue was harvested for gene expression analysis. 3T3-L1 adipocytes were treated with Tnf-α to mimic the inflammatory state and gene expression was detected by realtime PCR and Western blotting. Our results showed that NaB treatment improved glucose control in db/db mice as determined by GTT and ITT tests. Gene expression analysis showed that NaB inhibited cytokines and immunological markers including CD68, Interferon-γ and Mcp in adipose tissues in db/db mice. Moreover, NaB inhibited cytokine releasing in 3T3-L1 adipocytes treated with TNF-α. Further analysis of inflammation pathway showed that NLRP3 was activated in db/db mice, which was efficiently inhibited by NaB treatment. Our data suggest that inhibition of obesity-induced inflammation alleviates IR, and NaB might be a potential anti-inflammatory agent for obesity.
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Affiliation(s)
- Xukai Wang
- Department of Cardiovascular Internal Medicine, Institute of Field Surgery, Daping Hospital, Third Military Medical University, Chongqing, China
| | - Gang He
- Department of Medical Genetics, College of Basic Medicine, Third Military Medical University, Chongqing, China
| | - Yan Peng
- Department of Cardiovascular Internal Medicine, Institute of Field Surgery, Daping Hospital, Third Military Medical University, Chongqing, China
| | - Weitian Zhong
- Department of Cardiovascular Internal Medicine, Institute of Field Surgery, Daping Hospital, Third Military Medical University, Chongqing, China
| | - Yan Wang
- Department of Medical Genetics, College of Basic Medicine, Third Military Medical University, Chongqing, China
| | - Bo Zhang
- Department of Medical Genetics, College of Basic Medicine, Third Military Medical University, Chongqing, China
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Ortiz VE, Kwo J. Obesity: physiologic changes and implications for preoperative management. BMC Anesthesiol 2015; 15:97. [PMID: 26141622 PMCID: PMC4491231 DOI: 10.1186/s12871-015-0079-8] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2014] [Accepted: 06/24/2015] [Indexed: 02/08/2023] Open
Abstract
The proportion of patients defined as obese continues to grow in many westernized nations, particularly the United States (USA). This trend has shifted the perioperative management of obese patients into the realm of routine care. As obese patients present for all types of procedures, it is crucial for anesthesiologists, surgeons, internists, and perioperative health care providers alike to have a firm understanding of their altered multi-organ physiology in order to safely prepare the obese patient for an operation. A careful preoperative evaluation may also serve to identify risk factors for postoperative adverse events. Subsequently, preoperative measures may be implemented to mitigate these complications. In this manuscript we address the major considerations for the preoperative evaluation of the severely obese patient.
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Affiliation(s)
- Vilma E Ortiz
- Department of Anesthesia, Critical Care & Pain Medicine, Associate Anesthetist, Massachusetts General Hospital, 55 Fruit Street, Boston, MA, 02114, USA.
| | - Jean Kwo
- Department of Anesthesia, Critical Care & Pain Medicine, Associate Anesthetist, Massachusetts General Hospital, 55 Fruit Street, Boston, MA, 02114, USA.
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Bełtowski J, Guranowski A, Jamroz-Wiśniewska A, Wolski A, Hałas K. Hydrogen-sulfide-mediated vasodilatory effect of nucleoside 5'-monophosphorothioates in perivascular adipose tissue. Can J Physiol Pharmacol 2015; 93:585-95. [PMID: 26120822 DOI: 10.1139/cjpp-2014-0543] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Hydrogen sulfide (H2S) is synthesized in perivascular adipose tissue (PVAT) and induces vasorelaxation. We examined whether the sulfur-containing AMP and GMP analogs AMPS and GMPS can serve as the H2S donors in PVAT. H2S production by isolated rat periaortic adipose tissue (PAT) was measured with a polarographic sensor. In addition, phenylephrine-induced contractility of aortic rings with (+) or without (-) PAT was examined. Isolated PAT produced H2S from AMPS or GMPS in the presence of the P2X7 receptor agonist BzATP. Phenylephrine-induced contractility of PAT(+) rings was lower than of PAT(-) rings. AMPS or GMPS had no effect on the contractility of PAT(-) rings, but used together with BzATP reduced the contractility of PAT(+) rings when endogenous H2S production was inhibited with propargylglycine. A high-fat diet reduced endogenous H2S production by PAT. Interestingly, AMPS and GMPS were converted to H2S by PAT of obese rats, and reduced contractility of PAT(+) aortic rings isolated from these animals even in the absence of BzATP. We conclude that (i) AMPS and GMPS can be hydrolyzed to H2S by PAT when P2X7 receptors are activated, (ii) a high-fat diet impairs endogenous H2S production by PAT, (iii) AMPS and GMPS restore the anticontractile effects of PAT in obese animals without P2X7 stimulation.
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Affiliation(s)
- Jerzy Bełtowski
- a Department of Pathophysiology, Medical University, ul. Jaczewskiego 8, 20-090 Lublin, Poland
| | - Andrzej Guranowski
- b Department of Biochemistry and Biotechnology, Poznań University of Life Sciences, Poznań, Poland
| | | | - Andrzej Wolski
- d Department of Interventional Radiology and Neuroradiology, Medical University, Lublin, Poland
| | - Krzysztof Hałas
- d Department of Interventional Radiology and Neuroradiology, Medical University, Lublin, Poland
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