|
1
|
Mallya S, Gangadhar V, Aldrin SE, Acharya M, Kabekkodu SP, Kolathur KK, Chakrabarty S. Insights into the molecular and genetic role of obesity in breast cancer pathogenesis. Cancer Biol Ther 2025; 26:2501345. [PMID: 40353441 PMCID: PMC12077478 DOI: 10.1080/15384047.2025.2501345] [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: 01/21/2025] [Revised: 04/23/2025] [Accepted: 04/28/2025] [Indexed: 05/14/2025] Open
Abstract
The epidemic of obesity is a growing concern and is one of the major risk factors for several chronic diseases, including several types of cancers. The correlation of breast cancer with obesity has been extensively studied and involves an interplay of hormonal, metabolic, and genetic factors explored in this review. Inflammation and hormone dysregulation play an important role in promoting a protumorigenic environment through adipose tissue, which is involved in energy storage and functions as an endocrine organ. As a result, various cytokines, primarily proinflammatory in nature, are released, resulting in low-grade inflammation promoting tumor growth. Additionally, obese conditions also induce imbalances in hormones, particularly estrogen and insulin, both of which drive carcinogenesis. Genetic components such as single nucleotide polymorphisms also play critical roles in modulating the correlation between obesity and breast cancer. This review provides a comprehensive overview of various mechanisms underlying obesity and breast cancer incidence and progression.
Collapse
Affiliation(s)
- Sandeep Mallya
- Department of Bioinformatics, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, India
| | - Varsha Gangadhar
- Department of Bioinformatics, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, India
| | - Sophia Evangeline Aldrin
- Department of Bioinformatics, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, India
| | - Meghana Acharya
- Department of Bioinformatics, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, India
| | - Shama Prasada Kabekkodu
- Department of Cell and Molecular Biology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, India
| | - Kiran Kumar Kolathur
- Department of Pharmaceutical Biotechnology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, India
| | - Sanjiban Chakrabarty
- Department of Public Health and Genomics, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, India
| |
Collapse
|
|
2
|
Kurexi A, Peng J, Yao J, Wang L, Wang Q. Association of "a body shape index" with the risk of developing colorectal cancer in U.S. patients with metabolic syndrome: evidence from the NHANES 1999-2018. BMC Gastroenterol 2024; 24:447. [PMID: 39627686 PMCID: PMC11613469 DOI: 10.1186/s12876-024-03537-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2024] [Accepted: 11/22/2024] [Indexed: 12/08/2024] Open
Abstract
BACKGROUND Colorectal cancer (CRC) is the third most common cancer worldwide and presents a significant challenge to public health. Metabolic syndrome (MetS) is a condition that is predominantly characterized by abdominal obesity and metabolic abnormalities such as hypertension, hyperglycemia, and hyperlipidemia, and it is one of the critical risk factors for CRC. Traditional anthropometric measures have limitations in accurately assessing the risk associated with abdominal obesity. This study aimed to investigate the association between "A Body Shape Index" (ABSI) and the risk of developing CRC among individuals with MetS utilizing data from the National Health and Nutrition Examination Survey (NHANES). METHODS This cross-sectional study conducted a statistical analysis of all adult participants who met the diagnostic criteria for MetS in the NHANES data from 1999 to 2018. The ABSI was calculated to quantify abdominal obesity. ABSI is derived from a formula that incorporates waist circumference (WC), body mass index (BMI), and height, and is calculated as ABSI = WC / (BMI^(2/3) × Height^(1/2)). Multivariate logistic regression modeling was used to examine the independent association between ABSI and CRC incidence. Receiver Operating Characteristic (ROC) curves were employed to analyze the ability of ABSI compared to traditional metrics in identifying CRC risk. RESULTS This study involved 16,018 MetS patients with a mean age of 51.8 years, of whom 50.3% were male and 49.7% were female. Logistic regression adjusted for confounders revealed a significant association between an elevated ABSI and an increased risk of developing CRC (odds ratio (OR): 1.433, 95% confidence interval (CI): 1.116 to 1.841; P = 0.005). ROC analyses confirmed that the predictive accuracy of the ABSI for the risk of developing CRC area under the curve (AUC): (0.668, 95% CI: 0.624 to 0.713) surpassed that of traditional measurement methods. CONCLUSION Among individuals with MetS, the ABSI is linked to an elevated risk of developing CRC. Compared with traditional anthropometric indices, the ABSI is a superior predictive marker for the risk of developing CRC.
Collapse
Affiliation(s)
- Airepati Kurexi
- Gastrointestinal Surgery, Fourth Affiliated Hospital of Xinjiang Medical University, 116 Huanghe Road, Saybagh District, Urumqi, 830099, Xinjiang Uygur Autonomous Region, China
| | - Jingqi Peng
- Gastrointestinal Surgery, Fourth Affiliated Hospital of Xinjiang Medical University, 116 Huanghe Road, Saybagh District, Urumqi, 830099, Xinjiang Uygur Autonomous Region, China
| | - Juyi Yao
- Gastrointestinal Surgery, Fourth Affiliated Hospital of Xinjiang Medical University, 116 Huanghe Road, Saybagh District, Urumqi, 830099, Xinjiang Uygur Autonomous Region, China
| | - Lin Wang
- Gastrointestinal Surgery, Fourth Affiliated Hospital of Xinjiang Medical University, 116 Huanghe Road, Saybagh District, Urumqi, 830099, Xinjiang Uygur Autonomous Region, China
| | - Qisan Wang
- Gastrointestinal Surgery, Fourth Affiliated Hospital of Xinjiang Medical University, 116 Huanghe Road, Saybagh District, Urumqi, 830099, Xinjiang Uygur Autonomous Region, China.
| |
Collapse
|
|
3
|
Miracle CE, McCallister CL, Egleton RD, Salisbury TB. Mechanisms by which obesity regulates inflammation and anti-tumor immunity in cancer. Biochem Biophys Res Commun 2024; 733:150437. [PMID: 39074412 PMCID: PMC11455618 DOI: 10.1016/j.bbrc.2024.150437] [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: 05/10/2024] [Revised: 07/12/2024] [Accepted: 07/22/2024] [Indexed: 07/31/2024]
Abstract
Obesity is associated with an increased risk for 13 different cancers. The increased risk for cancer in obesity is mediated by obesity-associated changes in the immune system. Obesity has distinct effects on different types of inflammation that are tied to tumorigenesis. For example, obesity promotes chronic inflammation in adipose tissue that is tumor-promoting in peripheral tissues. Conversely, obesity inhibits acute inflammation that rejects tumors. Obesity therefore promotes cancer by differentially regulating chronic versus acute inflammation. Given that obesity is chronic, the initial inflammation in adipose tissue will lead to systemic inflammation that could induce compensatory anti-inflammatory reactions in peripheral tissues to suppress chronic inflammation. The overall effect of obesity in peripheral tissues is therefore dependent on the duration and severity of obesity. Adipose tissue is a complex tissue that is composed of many cell types in addition to adipocytes. Further, adipose tissue cellularity is different at different anatomical sites throughout the body. Consequently, the sensitivity of adipose tissue to obesity is dependent on the anatomical location of the adipose depot. For example, obesity induces more inflammation in visceral than subcutaneous adipose tissue. Based on these studies, the mechanisms by which obesity promotes tumorigenesis are multifactorial and immune cell type-specific. The objective of our paper is to discuss the cellular mechanisms by which obesity promotes tumorigenesis by regulating distinct types of inflammation in adipose tissue and the tumor microenvironment.
Collapse
Affiliation(s)
- Cora E Miracle
- Department of Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, 1 John Marshall Drive, Huntington, WV, 25755, USA.
| | - Chelsea L McCallister
- Department of Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, 1 John Marshall Drive, Huntington, WV, 25755, USA.
| | - Richard D Egleton
- Department of Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, 1 John Marshall Drive, Huntington, WV, 25755, USA.
| | - Travis B Salisbury
- Department of Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, 1 John Marshall Drive, Huntington, WV, 25755, USA.
| |
Collapse
|
|
4
|
Lagarde CB, Thapa K, Cullen NM, Hawes ML, Salim K, Benz MC, Dietrich SR, Burow BE, Bunnell BA, Martin EC, Collins-Burow BM, Lynch RM, Hoang VT, Burow ME, Fang JS. Obesity and leptin in breast cancer angiogenesis. Front Endocrinol (Lausanne) 2024; 15:1465727. [PMID: 39439572 PMCID: PMC11493622 DOI: 10.3389/fendo.2024.1465727] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2024] [Accepted: 09/04/2024] [Indexed: 10/25/2024] Open
Abstract
At the time of breast cancer diagnosis, most patients meet the diagnostic criteria to be classified as obese or overweight. This can significantly impact patient outcome: breast cancer patients with obesity (body mass index > 30) have a poorer prognosis compared to patients with a lean BMI. Obesity is associated with hyperleptinemia, and leptin is a well-established driver of metastasis in breast cancer. However, the effect of hyperleptinemia on angiogenesis in breast cancer is less well-known. Angiogenesis is an important process in breast cancer because it is essential for tumor growth beyond 1mm3 in size as well as cancer cell circulation and metastasis. This review investigates the role of leptin in regulating angiogenesis, specifically within the context of breast cancer and the associated tumor microenvironment in obese patients.
Collapse
Affiliation(s)
- Courtney B. Lagarde
- Department of Medicine, Section of Hematology and Oncology, Tulane University School of Medicine, New Orleans, LA, United States
- Tulane University Cancer Center, New Orleans, LA, United States
| | - Kapil Thapa
- Department of Cell and Molecular Biology, Tulane University School of Science and Engineering, New Orleans, LA, United States
| | - Nicole M. Cullen
- Department of Medicine, Section of Hematology and Oncology, Tulane University School of Medicine, New Orleans, LA, United States
- Tulane University Cancer Center, New Orleans, LA, United States
| | - Mackenzie L. Hawes
- Department of Medicine, Section of Hematology and Oncology, Tulane University School of Medicine, New Orleans, LA, United States
- Tulane University Cancer Center, New Orleans, LA, United States
| | - Khudeja Salim
- Department of Medicine, Section of Hematology and Oncology, Tulane University School of Medicine, New Orleans, LA, United States
- Tulane University Cancer Center, New Orleans, LA, United States
| | - Megan C. Benz
- Department of Medicine, Section of Hematology and Oncology, Tulane University School of Medicine, New Orleans, LA, United States
- Tulane University Cancer Center, New Orleans, LA, United States
| | - Sophie R. Dietrich
- Department of Medicine, Section of Hematology and Oncology, Tulane University School of Medicine, New Orleans, LA, United States
- Tulane University Cancer Center, New Orleans, LA, United States
- United States Department of Agriculture Southern Regional Research Center, New Orleans, LA, United States
| | - Brandon E. Burow
- Department of Cell and Molecular Biology, Tulane University School of Science and Engineering, New Orleans, LA, United States
| | - Bruce A. Bunnell
- Department of Microbiology, Immunology, and Genetics, University of North Texas Health Science Center, Fort Worth, TX, United States
| | - Elizabeth C. Martin
- Department of Medicine, Section of Hematology and Oncology, Tulane University School of Medicine, New Orleans, LA, United States
- Tulane University Cancer Center, New Orleans, LA, United States
| | - Bridgette M. Collins-Burow
- Department of Medicine, Section of Hematology and Oncology, Tulane University School of Medicine, New Orleans, LA, United States
- Tulane University Cancer Center, New Orleans, LA, United States
| | - Ronald M. Lynch
- Department of Physiology, College of Medicine, University of Arizona, Tucson, AZ, United States
| | - Van T. Hoang
- Department of Medicine, Section of Hematology and Oncology, Tulane University School of Medicine, New Orleans, LA, United States
- Tulane University Cancer Center, New Orleans, LA, United States
| | - Matthew E. Burow
- Department of Medicine, Section of Hematology and Oncology, Tulane University School of Medicine, New Orleans, LA, United States
- Tulane University Cancer Center, New Orleans, LA, United States
- Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA, United States
- Department of Surgery, Tulane University School of Medicine, New Orleans, LA, United States
| | - Jennifer S. Fang
- Department of Cell and Molecular Biology, Tulane University School of Science and Engineering, New Orleans, LA, United States
- Department of Physiology, Tulane University School of Medicine, New Orleans, LA, United States
| |
Collapse
|
|
5
|
Liu Y, Zhao D, Chai S, Zhang X. Association of visceral adipose tissue with albuminuria and interaction between visceral adiposity and diabetes on albuminuria. Acta Diabetol 2024; 61:909-916. [PMID: 38558152 PMCID: PMC11182824 DOI: 10.1007/s00592-024-02271-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2024] [Accepted: 03/03/2024] [Indexed: 04/04/2024]
Abstract
AIMS To explore the correlation between visceral adipose tissue and albuminuria, and whether there is interaction between visceral adipose tissue and diabetes on albuminuria. METHODS The study subjects were adult subjects (age ≥ 18 years) from the National Health and Nutrition Examination Surveys (NHANES) database of the USA in 2017-2018. Visceral fat area (VFA) was measured by dual-energy X-ray absorptiometry (DXA). Subjects were divided into three groups according to VFA: low (VFA 0-60cm2), medium (VFA 60-120 cm2) and high (VFA ≥ 120 cm2). Albuminuria was defined as urinary albumin-to-creatinine ratio (UACR) ≥ 30 mg/g. The statistical analysis software used is STATA 17.0. RESULTS Data pertaining to 2965 participants (2706 without albuminuria) were included in the analysis. High VFA is an independent risk factor for albuminuria (OR 1.367, 95% CI 1.023-1.827). In the low-VFA group, there is no significant association between diabetes and albuminuria (OR 1.415, 95% CI 0.145-13.849). In the medium-VFA group, diabetes is an independent risk factor for albuminuria (OR 2.217, 95% CI 1.095-4.488). In the high-VFA group, diabetes is also an independent risk factor for albuminuria (OR 5.150, 95% CI 3.150-8.421). There is an additive interaction between high VFA (VFA ≥ 120 cm2) and diabetes on the effect of albuminuria (RERI 3.757, 95% CI 0.927-6.587, p = 0.009), while no multiplication interaction (OR 1.881, 95% CI 0.997-1.023, p = 0.141). CONCLUSIONS High VFA may represent an independent risk factor for albuminuria. The amount of visceral fat may affect the effect of diabetes on albuminuria. The higher the visceral fat, the stronger the correlation between diabetes and albuminuria should be present. We suppose an additive interaction between VFA and diabetes on the effect of albuminuria.
Collapse
Affiliation(s)
- Yufang Liu
- Department of Endocrinology, Peking University International Hospital, Beijing, 102206, People's Republic of China
| | - Dan Zhao
- Department of Endocrinology, Peking University International Hospital, Beijing, 102206, People's Republic of China
| | - Sanbao Chai
- Department of Endocrinology, Peking University International Hospital, Beijing, 102206, People's Republic of China
| | - Xiaomei Zhang
- Department of Endocrinology, Peking University International Hospital, Beijing, 102206, People's Republic of China.
| |
Collapse
|
|
6
|
Bartkowiak K, Bartkowiak M, Jankowska-Steifer E, Ratajska A, Kujawa M, Aniołek O, Niderla-Bielińska J. Metabolic Syndrome and Cardiac Vessel Remodeling Associated with Vessel Rarefaction: A Possible Underlying Mechanism May Result from a Poor Angiogenic Response to Altered VEGF Signaling Pathways. J Vasc Res 2024; 61:151-159. [PMID: 38615659 DOI: 10.1159/000538361] [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: 11/15/2023] [Accepted: 03/09/2024] [Indexed: 04/16/2024] Open
Abstract
BACKGROUND Elevated mortality rates in patients with metabolic syndrome (MetS) are partly due to adverse remodeling of multiple organs, which may lead to cardiovascular disease, nonalcoholic fatty liver disease, kidney failure, or other conditions. MetS symptoms, such as obesity, hypertension, hyperglycemia, dyslipidemia, associated with insulin and leptin resistance, are recognized as major cardiovascular risk factors that adversely affect the heart. SUMMARY Pathological cardiac remodeling is accompanied by endothelial cell dysfunction which may result in diminished coronary flow, dysregulated oxygen demand/supply balance, as well as vessel rarefaction. The reduced number of vessels and delayed or inhibited formation of collaterals after myocardial infarction in MetS heart may be due to unfavorable changes in endothelial cell metabolism but also to altered expression of vascular endothelial growth factor molecules, their receptors, and changes in signal transduction from the cell membrane, which severely affect angiogenesis. KEY MESSAGES Given the established role of cardiac vessel endothelial cells in maintaining tissue homeostasis, defining the molecular background underlying vessel dysfunction associated with impaired angiogenesis is of great importance for future therapeutic purposes. Therefore, the aim of this paper was to present current information regarding vascular endothelial growth factor signaling in the myocardium of MetS individuals.
Collapse
Affiliation(s)
- Krzysztof Bartkowiak
- Department of Histology and Embryology, Medical University of Warsaw, Warsaw, Poland
| | - Mateusz Bartkowiak
- Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland
| | - Ewa Jankowska-Steifer
- Department of Histology and Embryology, Medical University of Warsaw, Warsaw, Poland
| | - Anna Ratajska
- Department of Pathology, Medical University of Warsaw, Warsaw, Poland
| | - Marek Kujawa
- Department of Histology and Embryology, Faculty of Medicine, Lazarski University, Warsaw, Poland
| | - Olga Aniołek
- Department of Histology and Embryology, Faculty of Medicine, Lazarski University, Warsaw, Poland
| | | |
Collapse
|
|
7
|
Pinto E, Meneghel P, Farinati F, Russo FP, Pelizzaro F, Gambato M. Efficacy of immunotherapy in hepatocellular carcinoma: Does liver disease etiology have a role? Dig Liver Dis 2024; 56:579-588. [PMID: 37758610 DOI: 10.1016/j.dld.2023.08.062] [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: 07/02/2023] [Revised: 08/18/2023] [Accepted: 08/30/2023] [Indexed: 09/29/2023]
Abstract
The systemic treatment of hepatocellular carcinoma (HCC) is changing rapidly. After a decade of tyrosine kinase inhibitors (TKIs), as the only therapeutic option for the treatment of advanced HCC, in the last few years several phase III trials demonstrated the efficacy of immune checkpoint inhibitors (ICIs). The combination of the anti-PD-L1 atezolizumab and the anti-vascular endothelial growth factor (VEGF) bevacizumab demonstrated the superiority over sorafenib and currently represents the standard of care treatment for advanced HCC. In addition, the combination of durvalumab (an anti-PD-L1) and tremelimumab (an anti-CTLA4) proved to be superior to sorafenib, and in the same trial durvalumab monotherapy showed non-inferiority compared to sorafenib. However, early reports suggest an influence of HCC etiology in modulating the response to these drugs. In particular, a lower effectiveness of ICIs has been suggested in patients with non-viral HCC (in particular non-alcoholic fatty liver disease). Nevertheless, randomized controlled trials available to date have not been stratified for etiology and data suggesting a possible impact of etiology in the outcome of patients managed with ICIs derive from subgroup not pre-specified analyses. In this review, we aim to examine the potential impact of HCC etiology on the response to immunotherapy regimens for HCC.
Collapse
Affiliation(s)
- Elisa Pinto
- Gastroenterology and Multivisceral Transplant Unit, Padua University Hospital, Padua, Italy
| | - Paola Meneghel
- Gastroenterology and Multivisceral Transplant Unit, Padua University Hospital, Padua, Italy
| | - Fabio Farinati
- Gastroenterology and Multivisceral Transplant Unit, Padua University Hospital, Padua, Italy
| | - Francesco Paolo Russo
- Gastroenterology and Multivisceral Transplant Unit, Padua University Hospital, Padua, Italy.
| | - Filippo Pelizzaro
- Gastroenterology and Multivisceral Transplant Unit, Padua University Hospital, Padua, Italy
| | - Martina Gambato
- Gastroenterology and Multivisceral Transplant Unit, Padua University Hospital, Padua, Italy.
| |
Collapse
|
|
8
|
Listyoko AS, Okazaki R, Harada T, Inui G, Yamasaki A. Impact of obesity on airway remodeling in asthma: pathophysiological insights and clinical implications. FRONTIERS IN ALLERGY 2024; 5:1365801. [PMID: 38562155 PMCID: PMC10982419 DOI: 10.3389/falgy.2024.1365801] [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: 01/05/2024] [Accepted: 03/07/2024] [Indexed: 04/04/2024] Open
Abstract
The prevalence of obesity among asthma patients has surged in recent years, posing a significant risk factor for uncontrolled asthma. Beyond its impact on asthma severity and patients' quality of life, obesity is associated with reduced lung function, increased asthma exacerbations, hospitalizations, heightened airway hyperresponsiveness, and elevated asthma-related mortality. Obesity may lead to metabolic dysfunction and immune dysregulation, fostering chronic inflammation characterized by increased pro-inflammatory mediators and adipocytokines, elevated reactive oxygen species, and reduced antioxidant activity. This chronic inflammation holds the potential to induce airway remodeling in individuals with asthma and obesity. Airway remodeling encompasses structural and pathological changes, involving alterations in the airway's epithelial and subepithelial layers, hyperplasia and hypertrophy of airway smooth muscle, and changes in airway vascularity. In individuals with asthma and obesity, airway remodeling may underlie heightened airway hyperresponsiveness and increased asthma severity, ultimately contributing to the development of persistent airflow limitation, declining lung function, and a potential increase in asthma-related mortality. Despite efforts to address the impact of obesity on asthma outcomes, the intricate mechanisms linking obesity to asthma pathophysiology, particularly concerning airway remodeling, remain incompletely understood. This comprehensive review discusses current research investigating the influence of obesity on airway remodeling, to enhance our understanding of obesity's role in the context of asthma airway remodeling.
Collapse
Affiliation(s)
- Aditya Sri Listyoko
- Division of Respiratory Medicine and Rheumatology, Department of Multidisciplinary Internal Medicine, Faculty of Medicine, Tottori University, Yonago, Japan
- Pulmonology and Respiratory Medicine Department, Faculty of Medicine, Brawijaya University-Dr. Saiful Anwar General Hospital, Malang, Indonesia
| | - Ryota Okazaki
- Division of Respiratory Medicine and Rheumatology, Department of Multidisciplinary Internal Medicine, Faculty of Medicine, Tottori University, Yonago, Japan
| | - Tomoya Harada
- Division of Respiratory Medicine and Rheumatology, Department of Multidisciplinary Internal Medicine, Faculty of Medicine, Tottori University, Yonago, Japan
| | - Genki Inui
- Division of Respiratory Medicine and Rheumatology, Department of Multidisciplinary Internal Medicine, Faculty of Medicine, Tottori University, Yonago, Japan
| | - Akira Yamasaki
- Division of Respiratory Medicine and Rheumatology, Department of Multidisciplinary Internal Medicine, Faculty of Medicine, Tottori University, Yonago, Japan
| |
Collapse
|
|
9
|
Mallick R, Basak S, Das RK, Banerjee A, Paul S, Pathak S, Duttaroy AK. Fatty Acids and their Proteins in Adipose Tissue Inflammation. Cell Biochem Biophys 2024; 82:35-51. [PMID: 37794302 PMCID: PMC10867084 DOI: 10.1007/s12013-023-01185-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/20/2023] [Indexed: 10/06/2023]
Abstract
Chronic low-grade adipose tissue inflammation is associated with metabolic disorders. Inflammation results from the intertwined cross-talks of pro-inflammatory and anti-inflammatory pathways in the immune response of adipose tissue. In addition, adipose FABP4 levels and lipid droplet proteins are involved in systemic and tissue inflammation. Dysregulated adipocytes help infiltrate immune cells derived from bone marrow responsible for producing cytokines and chemokines. When adipose tissue expands in excess, adipocyte exhibits increased secretion of adipokines and is implicated in metabolic disturbances due to the release of free fatty acids. This review presents an emerging concept in adipose tissue fat metabolism, fatty acid handling and binding proteins, and lipid droplet proteins and their involvement in inflammatory disorders.
Collapse
Affiliation(s)
- Rahul Mallick
- A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland
| | - Sanjay Basak
- Molecular Biology Division, ICMR-National Institute of Nutrition, Indian Council of Medical Research, Hyderabad, India
| | - Ranjit K Das
- Department of Health and Biomedical Sciences, University of Texas Rio Grande Valley, Brownsville, TX, USA
| | - Antara Banerjee
- Chettinad Academy of Research and Education (CARE), Chettinad Hospital and Research Institute (CHRI), Department of Medical Biotechnology, Faculty of Allied Health Sciences, Chennai, India
| | - Sujay Paul
- Tecnologico de Monterrey, School of Engineering and Sciences, Campus Queretaro, Av. Epigmenio Gonzalez, No. 500 Fracc, San Pablo, Queretaro, 76130, Mexico
| | - Surajit Pathak
- Chettinad Academy of Research and Education (CARE), Chettinad Hospital and Research Institute (CHRI), Department of Medical Biotechnology, Faculty of Allied Health Sciences, Chennai, India
| | - Asim K Duttaroy
- Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, POB 1046 Blindern, Oslo, Norway.
| |
Collapse
|
|
10
|
Chen J, Li YT, Niu Z, He Z, Xie YJ, Hernandez J, Huang W, Wang HHX. Association of Visceral Obesity Indices With Incident Diabetic Retinopathy in Patients With Diabetes: Prospective Cohort Study. JMIR Public Health Surveill 2024; 10:e48120. [PMID: 38319705 PMCID: PMC10879974 DOI: 10.2196/48120] [Citation(s) in RCA: 14] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2023] [Revised: 07/31/2023] [Accepted: 12/16/2023] [Indexed: 02/07/2024] Open
Abstract
BACKGROUND Visceral adipose tissue plays an active role in the pathogenesis of type 2 diabetes and vascular dysfunction. The lipid accumulation product (LAP), visceral adiposity index (VAI), and Chinese VAI (CVAI) have been proposed as simple and validated surrogate indices for measuring visceral adipose tissue. However, the evidence from prospective studies on the associations between these novel indices of visceral obesity and diabetic retinopathy (DR) remains scant. OBJECTIVE This study aimed to investigate the longitudinal associations of LAP, VAI, and CVAI with incident DR in Chinese patients with diabetes. METHODS This was a prospective cohort study conducted in Guangzhou in southern China. We collected baseline data between November 2017 and July 2020, while on-site follow-up visits were conducted annually until January 2022. The study participants consisted of 1403 patients with a clinical diagnosis of diabetes, referred from primary care, who were free of DR at baseline. The LAP, VAI, and CVAI levels were calculated by sex-specific equations based on anthropometric and biochemical parameters. DR was assessed using 7-field color stereoscopic fundus photographs and graded according to the modified Airlie House Classification scheme. Time-dependent Cox proportional hazard models were constructed to estimate the hazard ratios with 95% CIs. Restricted cubic spline curves were fitted to examine the dose-response relationship between the 3 indices of visceral obesity and new-onset DR. Subgroup analyses were performed to investigate the potential effect modifiers. RESULTS The mean age of study participants was 64.5 (SD 7.6) years, and over half (816/1403, 58.2%) were female. During a median follow-up of 2.13 years, 406 DR events were observed. A 1-SD increment in LAP, VAI, or CVAI was consistently associated with increased risk for new-onset DR, with a multivariable‑adjusted hazard ratio of 1.24 (95% CI 1.09-1.41; P=.001), 1.22 (95% CI 1.09-1.36; P<.001), and 1.48 (95% CI 1.19-1.85; P=.001), respectively. Similar patterns were observed across tertiles in LAP (P for trend=.001), VAI (P for trend<.001), and CVAI (P for trend=.009). Patients in the highest tertile of LAP, VAI, and CVAI had an 84%, 86%, and 82% higher hazard of DR, respectively, compared to those in the lowest tertile. A nonlinear dose-response relationship with incident DR was noted for LAP and VAI (both P for nonlinearity<.05), but not for CVAI (P for nonlinearity=.51). We did not detect the presence of effect modification by age, sex, duration of diabetes, BMI, or comorbidity (all P for interaction>.10). CONCLUSIONS Visceral obesity, as measured by LAP, VAI, or CVAI, is independently associated with increased risk for new-onset DR in Chinese patients with diabetes. Our findings may suggest the necessity of incorporating regular monitoring of visceral obesity indices into routine clinical practice to enhance population-based prevention for DR.
Collapse
Affiliation(s)
- Jiaheng Chen
- School of Public Health, Sun Yat-Sen University, Guangzhou, China
| | - Yu Ting Li
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, China
| | - Zimin Niu
- School of Public Health, Sun Yat-Sen University, Guangzhou, China
| | - Zhanpeng He
- Liwan Central Hospital of Guangzhou, Guangzhou, China
| | - Yao Jie Xie
- School of Nursing, The Hong Kong Polytechnic University, Hung Hom, Kowloon, China (Hong Kong)
| | - Jose Hernandez
- Faculty of Medicine and Health, EDU, Digital Education Holdings Ltd, Kalkara, Malta
- Green Templeton College, University of Oxford, Oxford, United Kingdom
| | - Wenyong Huang
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, China
| | - Harry H X Wang
- School of Public Health, Sun Yat-Sen University, Guangzhou, China
- JC School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, China (Hong Kong)
- Usher Institute, Deanery of Molecular, Genetic & Population Health Sciences, The University of Edinburgh, Edinburgh, United Kingdom
| |
Collapse
|
|
11
|
Altmäe S, Plaza-Florido A, Esteban FJ, Anguita-Ruiz A, Krjutškov K, Katayama S, Einarsdottir E, Kere J, Radom-Aizik S, Ortega FB. Effects of exercise on whole-blood transcriptome profile in children with overweight/obesity. Am J Hum Biol 2024; 36:e23983. [PMID: 37715654 PMCID: PMC11482632 DOI: 10.1002/ajhb.23983] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2023] [Revised: 08/23/2023] [Accepted: 08/24/2023] [Indexed: 09/18/2023] Open
Abstract
BACKGROUND The current knowledge about the molecular mechanisms underlying the health benefits of exercise is still limited, especially in childhood. We set out to investigate the effects of a 20-week exercise intervention on whole-blood transcriptome profile (RNA-seq) in children with overweight/obesity. METHODS Twenty-four children (10.21 ± 1.33 years, 46% girls) with overweight/obesity, were randomized to either a 20-week exercise program (intervention group; n = 10), or to a no-exercise control group (n = 14). Whole-blood transcriptome profile was analyzed using RNA-seq by STRT technique with GlobinLock technology. RESULTS Following the 20-week exercise intervention program, 161 genes were differentially expressed between the exercise and the control groups among boys, and 121 genes among girls (p-value <0.05), while after multiple correction, no significant difference between exercise and control groups persisted in gene expression profiles (FDR >0.05). Genes enriched in GO processes and molecular pathways showed different immune response in boys (antigen processing and presentation, infections, and T cell receptor complex) and in girls (Fc epsilon RI signaling pathway) (FDR <0.05). CONCLUSION These results suggest that 20-week exercise intervention program alters the molecular pathways involved in immune processes in children with overweight/obesity.
Collapse
Affiliation(s)
- Signe Altmäe
- Department of Biochemistry and Molecular Biology, Faculty of Sciences, University of Granada, Granada, Spain
- Instituto de Investigación Biosanitaria ibs.GRANADA, Granada, Spain
- Division of Obstetrics and Gynecology, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden
| | - Abel Plaza-Florido
- Department of Physical Education and Sports, Faculty of Sport Sciences, Sport and Health University Research Institute (iMUDS), University of Granada Granada, Granada, Spain
- Pediatric Exercise and Genomics Research Center, Department of Pediatrics, School of Medicine, University of California at Irvine, Irvine, California, USA
| | - Francisco J. Esteban
- Systems Biology Unit, Department of Experimental Biology, Faculty of Experimental Sciences, University of Jaen, Jaen, Spain
| | - Augusto Anguita-Ruiz
- Barcelona Institute for Global Health, ISGlobal Barcelona, Barcelona, Spain
- Department of Biochemistry and Molecular Biology II, School of Pharmacy, University of Granada Granada, Granada, Spain
- Center of Biomedical Research, Institute of Nutrition and Food Technology "José Mataix", University of Granada, Granada, Spain
- CIBEROBN (CIBER Physiopathology of Obesity and Nutrition), Instituto de Salud Carlos III, Madrid, Spain
| | - Kaarel Krjutškov
- Competence Centre for Health Technologies, Tartu, Estonia
- Department of Obstetrics and Gynaecology, Institute of Clinical Medicine, University of Tartu, Tartu, Estonia
| | - Shintaro Katayama
- Folkhälsan Research Center, Helsinki, Finland
- Stem Cells and Metabolism Research Program, Research Programs Unit, University of Helsinki, Finland
- Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden
| | - Elisabet Einarsdottir
- Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden
- Science for Life Laboratory, Department of Gene Technology, KTH-Royal Institute of Technology, Solna, Sweden
| | - Juha Kere
- Folkhälsan Research Center, Helsinki, Finland
- Stem Cells and Metabolism Research Program, Research Programs Unit, University of Helsinki, Finland
- Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden
| | - Shlomit Radom-Aizik
- Pediatric Exercise and Genomics Research Center, Department of Pediatrics, School of Medicine, University of California at Irvine, Irvine, California, USA
| | - Francisco B. Ortega
- Department of Physical Education and Sports, Faculty of Sport Sciences, Sport and Health University Research Institute (iMUDS), University of Granada Granada, Granada, Spain
- Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden
- Faculty of Sport and Health Sciences, University of Jyväskylä, Jyväskylä, Finland
- CIBERobn Physiopathology of Obesity and Nutrition, Granada, Spain
| |
Collapse
|
|
12
|
Chen Y, Kong W, Liu M, Li Q, Wang Y, Zheng Y, Zhou Y. Metabolic syndrome and risk of colorectal cancer: A Mendelian randomization study. Heliyon 2024; 10:e23872. [PMID: 38223733 PMCID: PMC10784169 DOI: 10.1016/j.heliyon.2023.e23872] [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: 04/01/2023] [Revised: 12/01/2023] [Accepted: 12/14/2023] [Indexed: 01/16/2024] Open
Abstract
Background Observational studies have previously demonstrated a significant relationship among both metabolic syndrome (Mets) and colorectal cancer (CRC). Whether there is a causal link remains controversial. Objective To clarify whether Mets and their components have a causal effect on colorectal cancer, we have carried out a bidirectional Mendelian randomization analysis (MR). Methods This study started from genome-wide association data for Mets and its 5 components (hypertension, waist circumference, fasting blood glucose, serum triglycerides, and serum high-density lipoprotein cholesterol) and colorectal cancer. Mendelian randomization (MR) techniques were used in the study to examine their associations. Results After Benjamini-Hochberg multiple corrections, genetically predicted significant causal link exists between WC (waist circumference) and CRC. The OR was 1.35 (95 % CI: 1.08-1.69; p = 0.0096). Other Mets components (HBP, FBG, TG, HDL), on the other hand, found no evidence of a genetic link between CRC and Mets. In addition, MR results showed that CRC was not causally related to either Mets or the components. We get the same result in the validated dataset. Conclusion According to the bidirectional MR investigation shows a significant causal relationship among obesity and CRC in the Mets component but no causal relationship in the opposite direction.
Collapse
Affiliation(s)
- Yuhua Chen
- The First Clinical Medical College, Lanzhou University, Lanzhou, China
- Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, China
- Key Laboratory for Gastrointestinal Diseases of Gansu Province, The First Hospital of Lanzhou University, Lanzhou, China
| | - Wanru Kong
- Department of Infection Management, Gansu Provincial Hospital, Lanzhou, 730000, China
| | - Min Liu
- Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, China
- Key Laboratory for Gastrointestinal Diseases of Gansu Province, The First Hospital of Lanzhou University, Lanzhou, China
| | - Qiang Li
- Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, China
- Key Laboratory for Gastrointestinal Diseases of Gansu Province, The First Hospital of Lanzhou University, Lanzhou, China
| | - Yuping Wang
- Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, China
- Key Laboratory for Gastrointestinal Diseases of Gansu Province, The First Hospital of Lanzhou University, Lanzhou, China
| | - Ya Zheng
- Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, China
- Key Laboratory for Gastrointestinal Diseases of Gansu Province, The First Hospital of Lanzhou University, Lanzhou, China
| | - Yongning Zhou
- Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, China
- Key Laboratory for Gastrointestinal Diseases of Gansu Province, The First Hospital of Lanzhou University, Lanzhou, China
| |
Collapse
|
|
13
|
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.
Collapse
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.
| |
Collapse
|
|
14
|
Pizzo TRF, Valverde AP, Orzari LE, Terciotti LG, de Lima RD, Costa do Bomfim FR, Esquisatto MAM, de Andrade TAM, Corezola do Amaral ME, de Oliveira CA, Felonato M. Caloric restriction improves inflammation in different tissues of the Wistar rats with obesity and 2K1C renovascular hypertension. Can J Physiol Pharmacol 2023; 101:661-671. [PMID: 37746936 DOI: 10.1139/cjpp-2022-0452] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/26/2023]
Abstract
Renovascular hypertension (RHV) is the cause of high blood pressure due to left renal ischemia, and obesity and hypertension cause an inflammatory response. This work analyzed the inflammatory and tissue repair profile in renal, hepatic, and cardiac tissues in an animal model of RVH associated with a high-fat diet and caloric restriction. The expressions of RORγ-t, IL-17, T-bet, and TNF-α decreased and IFN-γ increased in the right kidney. In relation to the left kidney, caloric restriction decreased the expression of IFN-γ. In the liver, caloric restriction decreased RORγ-t, IL-17, and T-bet. Hypertension associated with obesity decreased the expression of IFN-γ, while caloric restriction increased. In the right kidney, hypertension and obesity, associated or not with caloric restriction, increased the area of collagen fibers. In the heart and liver, caloric restriction reduced the area of collagen fibers. Caloric restriction increased vascular endothelial growth factor, reduced levels of growth transformation factor-β1 (TGF-β), and increased collagen I in the left kidney. Hypertension/obesity, submitted or not having caloric restriction, increased TGF-β in liver. The results suggest that caloric restriction has beneficial effects in lowering blood pressure and regulating tissue proinflammatory cytokines. However, there was no change in the structure and composition of tissue repair markers.
Collapse
Affiliation(s)
- Thayane Rafaela Feola Pizzo
- Graduate Program of Biomedical Sciences, University Center of Herminio Ometto Foundation-FHO, Av. Dr. Maximiliano Baruto, 500-Jd. Universitário, 13607-339, Araras, São Paulo, Brasil
| | - Ana Paula Valverde
- Graduate Program of Biomedical Sciences, University Center of Herminio Ometto Foundation-FHO, Av. Dr. Maximiliano Baruto, 500-Jd. Universitário, 13607-339, Araras, São Paulo, Brasil
| | - Lucas Eduardo Orzari
- Graduate Program of Biomedical Sciences, University Center of Herminio Ometto Foundation-FHO, Av. Dr. Maximiliano Baruto, 500-Jd. Universitário, 13607-339, Araras, São Paulo, Brasil
| | - Luiz Gustavo Terciotti
- Graduate Program of Biomedical Sciences, University Center of Herminio Ometto Foundation-FHO, Av. Dr. Maximiliano Baruto, 500-Jd. Universitário, 13607-339, Araras, São Paulo, Brasil
| | - Robson Damasceno de Lima
- Graduate Program of Biomedical Sciences, University Center of Herminio Ometto Foundation-FHO, Av. Dr. Maximiliano Baruto, 500-Jd. Universitário, 13607-339, Araras, São Paulo, Brasil
| | - Fernando Russo Costa do Bomfim
- Graduate Program of Biomedical Sciences, University Center of Herminio Ometto Foundation-FHO, Av. Dr. Maximiliano Baruto, 500-Jd. Universitário, 13607-339, Araras, São Paulo, Brasil
| | - Marcelo Augusto Marreto Esquisatto
- Graduate Program of Biomedical Sciences, University Center of Herminio Ometto Foundation-FHO, Av. Dr. Maximiliano Baruto, 500-Jd. Universitário, 13607-339, Araras, São Paulo, Brasil
| | - Thiago Antônio Moretti de Andrade
- Graduate Program of Biomedical Sciences, University Center of Herminio Ometto Foundation-FHO, Av. Dr. Maximiliano Baruto, 500-Jd. Universitário, 13607-339, Araras, São Paulo, Brasil
| | - Maria Esméria Corezola do Amaral
- Graduate Program of Biomedical Sciences, University Center of Herminio Ometto Foundation-FHO, Av. Dr. Maximiliano Baruto, 500-Jd. Universitário, 13607-339, Araras, São Paulo, Brasil
| | - Camila Andrea de Oliveira
- Graduate Program of Biomedical Sciences, University Center of Herminio Ometto Foundation-FHO, Av. Dr. Maximiliano Baruto, 500-Jd. Universitário, 13607-339, Araras, São Paulo, Brasil
| | - Maíra Felonato
- Graduate Program of Biomedical Sciences, University Center of Herminio Ometto Foundation-FHO, Av. Dr. Maximiliano Baruto, 500-Jd. Universitário, 13607-339, Araras, São Paulo, Brasil
| |
Collapse
|
|
15
|
Parvaneh RR, Vajdi M, Shiraz AN, Khani M, Farshbaf SE, Farhangi MA. Prognostic value of circulating macrophage inhibitory cytokine 1-growth differentiation factor 15 (MIC-1/GDF15) in obesity: Relation with vascular endothelial growth factor (VEGF) and markers of oxidative stress. Nutr Health 2023; 29:707-713. [PMID: 35549472 DOI: 10.1177/02601060221099716] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Background: Macrophage inhibitory cytokine 1-Growth differentiation Factor 15 (MIC-1/GDF15) and vascular endothelial growth factor (VEGF) are novel regulators of obesity and energy homeostasis and food intake. Aims: In the current cross-sectional study, we aimed to evaluate MIC-1 and VEGF concentrations and their association with serum lipids and biomarkers of oxidative stress in obese individuals. Methods: Fifty six obese subjects, aged between 20-50 years old, participated in the current study. Anthropometric and nutritional parameters were assessed and serum and blood concentrations of MIC-1/GDF15, VEGF, markers of oxidative stress and serum lipids were evaluated. Results: Serum VEGF was strongly associated with serum lipids and MIC-1/GDF15 concentrations while serum MIC-1/GDF15 was associated with total cholesterol (TC) and VEGF levels. In multivariate regression analysis, serum VEGF, appetite and GPX were potent determinants of MIC-1/GDF15 concentrations while VEGF was only associated with serum MIC-1/GDF15. Conclusion: The findings of the current study demonstrated the association between MIC-1/GDF15 and VEGF. Moreover, a positive association between these cytokines and serum lipids, was also observed. The results suggest that MIC-1/GDF15 and VEGF might be considered as prognostic markers in obesity-related metabolic disorders. Although further mechanistic studies are needed to better clarify the underlying mechanism.
Collapse
Affiliation(s)
- Roghayeh Rahbar Parvaneh
- Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Mahdi Vajdi
- Department of Community Nutrition, Faculty of Nutrition, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Ata Nikfam Shiraz
- School of Nursing and Midwifery, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mohammad Khani
- Department of Community Nutrition, Faculty of Nutrition, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Sara Ebadpour Farshbaf
- Department of Community Nutrition, Faculty of Nutrition, Tabriz University of Medical Sciences, Tabriz, Iran
| | | |
Collapse
|
|
16
|
Shu Y, Zhou Q, Shao Y, Lin H, Qu S, Han W, Lv X, Bi Y. BMI and plasma lipid levels with risk of proliferative diabetic retinopathy: a univariable and multivariable Mendelian randomization study. Front Nutr 2023; 10:1099807. [PMID: 37771754 PMCID: PMC10524610 DOI: 10.3389/fnut.2023.1099807] [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: 11/16/2022] [Accepted: 08/24/2023] [Indexed: 09/30/2023] Open
Abstract
Background The study aimed to determine whether a causal effect exists between body mass index (BMI) or plasma lipid levels and proliferative diabetic retinopathy (PDR) risk in humans. Methods We utilized univariable (UVMR) and multivariable two-sample Mendelian randomization (MVMR) analyses to confirm the effects of BMI and plasma lipid levels on the risk of PDR. Genetic variants associated with BMI and three plasma lipids were obtained from GWAS summary datasets generated by many different consortia and were deposited in the MR-Base database. The GWAS summary data for PDR from the FinnGen biobank included 2,12,889 participants of European ancestry (8,681 cases and 2,04,208 controls). Inverse variance weighted (IVW) was applied as the main MR analysis. Sensitivity analysis was used to evaluate the robustness of our findings. Results In the UVMR analysis, the causal associations of genetically predicted BMI with PDR presented a positive association (OR = 1.120, 95% CI = 1.076-1.167, P < 0.001), and the lower HDL-C level was associated with a higher risk of PDR (OR = 0.898, 95% CI = 0.811-0.995, P = 0.040). No evidence of an association between LDL-C or TG levels (P > 0.05) and PDR risk was found. In the MVMR analysis controlling for the HDL-C level, there was strong evidence for a direct causal effect of BMI on the risk of PDR (OR = 1.106, 95%CI = 1.049, 1.166, P < 0.001, IVW). After adjusting for BMI, there was no evidence for a direct causal effect of the HDL-C level on the risk of PDR (OR = 0.911, 95% CI = 0.823, 1.008, P = 0.072). Sensitivity analyses confirmed that the results were reliable and stable. Conclusion Robust evidence was demonstrated for an independent, causal effect of BMI in increasing the risk of PDR. Further studies are required to understand the potential biological mechanisms underlying this causal relationship.
Collapse
Affiliation(s)
- Yiyang Shu
- Department of Ophthalmology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Qi Zhou
- Exam Center, School of Medicine, Tongji University, Shanghai, China
| | - Yuting Shao
- Department of Ophthalmology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Hui Lin
- Department of Ophthalmology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Shen Qu
- Department of Ophthalmology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Wenting Han
- Department of Ophthalmology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Xiao Lv
- Department of Ophthalmology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Yanlong Bi
- Department of Ophthalmology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China
- School of Medicine, Tongji Eye Institute, Tongji University, Shanghai, China
| |
Collapse
|
|
17
|
Lundqvist MH, Pereira MJ, Eriksson JW. Glucose-dependent inflammatory responses in obese compared to lean individuals. Endocrine 2023; 81:464-476. [PMID: 37400734 PMCID: PMC10403442 DOI: 10.1007/s12020-023-03433-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2023] [Accepted: 06/15/2023] [Indexed: 07/05/2023]
Abstract
PURPOSE Obesity is characterized by chronic inflammation that may contribute to insulin resistance and promote type 2 diabetes. We have investigated whether inflammatory responses to glycemic and insulinemic variations are altered in obese individuals. METHODS Eight obese and eight lean individuals without diabetes had undergone hyperinsulinemic-euglycemic-hypoglycemic and hyperglycemic clamps in a previous study. Using Proximity Extension Assay, 92 inflammatory markers were analyzed from plasma samples at fasting, hyperinsulinemia-euglycemia, hypoglycemia and hyperglycemia. RESULTS In all participants, hyperinsulinemia, hypoglycemia and hyperglycemia led to reductions of 11, 19 and 62 out of the 70 fully evaluable biomarkers, respectively. FGF-21 increased during both hypoglycemia and hyperglycemia while IL-6 and IL-10 increased during hypoglycemia. In obese vs lean participants, Oncostatin-M, Caspase-8 and 4E-BP1 were more markedly suppressed during hypoglycemia, whereas VEGF-A was more markedly suppressed during hyperglycemia. BMI correlated inversely with changes of PD-L1 and CD40 during hyperinsulinemia, Oncostatin-M, TNFSF14, FGF-21 and 4EBP-1 during hypoglycemia and CCL23, VEGF-A and CDCP1 during hyperglycemia (Rho ≤ -0.50). HbA1c correlated positively with changes of MCP-2 and IL-15-RA during hyperinsulinemia (Rho ≥ 0.51) and inversely with changes of CXCL1, MMP-1 and Axin-1 during hypoglycemia (Rho ≤ -0.55). M-value correlated positively with changes of IL-12B and VEGF-A during hyperglycemia (Rho ≥ 0.51). Results above were significant (p < 0.05). CONCLUSION Overall, hyperinsulinemia, hypo- and hyperglycemia led to suppression of several inflammatory markers and this tended to be more marked in individuals with obesity, insulin resistance and dysglycemia. Thus, acute glycemic or insulinemic variations do not seem to potentiate possible inflammatory pathways in the development of insulin resistance and disturbed glucose metabolism.
Collapse
Affiliation(s)
- Martin H Lundqvist
- Clinical Diabetology and Metabolism, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
| | - Maria J Pereira
- Clinical Diabetology and Metabolism, Department of Medical Sciences, Uppsala University, Uppsala, Sweden
| | | |
Collapse
|
|
18
|
Mubtasim N, Gollahon L. Characterizing 3T3-L1 MBX Adipocyte Cell Differentiation Maintained with Fatty Acids as an In Vitro Model to Study the Effects of Obesity. Life (Basel) 2023; 13:1712. [PMID: 37629569 PMCID: PMC10455818 DOI: 10.3390/life13081712] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2023] [Revised: 07/31/2023] [Accepted: 08/03/2023] [Indexed: 08/27/2023] Open
Abstract
The increasing prevalence of obesity has prompted intensive research into understanding its role in pathogenesis and designing appropriate treatments. To determine the signals generated from the interaction of fat cells with a target organ, a reliable white adipocyte model in vitro is needed. Differentiated fibroblasts are the most extensively studied using in vitro cell models of white adipocytes. However, it can be argued that differentiated fibroblasts minimally recapitulate the consequences of obesity. Here, we describe 3T3-L1 MBX cells as a culture model for studying obese adipocytes and their effects. Differentiation of 3T3-L1 MBX cells was at first optimized and then maintained in the presence of fatty acids cocktail combination to induce the obese condition. Lipid accumulation and adipokine secretion profiles were analyzed. Results showed that fatty acid-maintained, differentiated 3T3-L1 MBX cells had significantly greater accumulation of lipids and significant changes in the adipokine secretions in comparison to differentiated 3T3-L1 MBX cells maintained in medium without fatty acids. To elucidate the molecular changes associated with adipogenesis and lipid accumulation profile of 3T3-L1 MBX cells, we have also explored the expression of some of the regulatory proteins related to the development and maintenance of adipocytes from the preadipocyte lineage.
Collapse
Affiliation(s)
| | - Lauren Gollahon
- Department of Biological Sciences, Texas Tech University, 2500 Broadway, Lubbock, TX 79409, USA;
| |
Collapse
|
|
19
|
Islam MK, Islam MR, Rahman MH, Islam MZ, Hasan MM, Mamun MMI, Moni MA. Integrated bioinformatics and statistical approach to identify the common molecular mechanisms of obesity that are linked to the development of two psychiatric disorders: Schizophrenia and major depressive disorder. PLoS One 2023; 18:e0276820. [PMID: 37494308 PMCID: PMC10370737 DOI: 10.1371/journal.pone.0276820] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2021] [Accepted: 10/13/2022] [Indexed: 07/28/2023] Open
Abstract
Obesity is a chronic multifactorial disease characterized by the accumulation of body fat and serves as a gateway to a number of metabolic-related diseases. Epidemiologic data indicate that Obesity is acting as a risk factor for neuro-psychiatric disorders such as schizophrenia, major depression disorder and vice versa. However, how obesity may biologically interact with neurodevelopmental or neurological psychiatric conditions influenced by hereditary, environmental, and other factors is entirely unknown. To address this issue, we have developed a pipeline that integrates bioinformatics and statistical approaches such as transcriptomic analysis to identify differentially expressed genes (DEGs) and molecular mechanisms in patients with psychiatric disorders that are also common in obese patients. Biomarker genes expressed in schizophrenia, major depression, and obesity have been used to demonstrate such relationships depending on the previous research studies. The highly expressed genes identify commonly altered signalling pathways, gene ontology pathways, and gene-disease associations across disorders. The proposed method identified 163 significant genes and 134 significant pathways shared between obesity and schizophrenia. Similarly, there are 247 significant genes and 65 significant pathways that are shared by obesity and major depressive disorder. These genes and pathways increase the likelihood that psychiatric disorders and obesity are pathogenic. Thus, this study may help in the development of a restorative approach that will ameliorate the bidirectional relation between obesity and psychiatric disorder. Finally, we also validated our findings using genome-wide association study (GWAS) and whole-genome sequence (WGS) data from SCZ, MDD, and OBE. We confirmed the likely involvement of four significant genes both in transcriptomic and GWAS/WGS data. Moreover, we have performed co-expression cluster analysis of the transcriptomic data and compared it with the results of transcriptomic differential expression analysis and GWAS/WGS.
Collapse
Affiliation(s)
- Md Khairul Islam
- Dept. of Information Communication Technology, Islamic University, Kushtia, Bangladesh
| | - Md Rakibul Islam
- Dept. of Information Communication Technology, Islamic University, Kushtia, Bangladesh
| | - Md Habibur Rahman
- Dept. of Computer Science Engineering, Islamic University, Kushtia, Bangladesh
| | - Md Zahidul Islam
- Dept. of Information Communication Technology, Islamic University, Kushtia, Bangladesh
| | - Md Mehedi Hasan
- Department of Statistics, University of Rajshahi, Rajshahi, Bangladesh
| | - Md Mainul Islam Mamun
- Department of Applied Physics and Electronic Engineering, University of Rajshahi, Rajshahi, Bangladesh
| | - Mohammad Ali Moni
- Dept. of Computer Science and Engineering, Pabna University of Science and Technology, Pabna, Bangladesh
| |
Collapse
|
|
20
|
Yoshida H, Fujiwara K. Adipose tissue area is a predictive biomarker for the efficacy of pegylated liposomal doxorubicin in platinum-refractory/resistant ovarian cancer. Cancer Med 2023. [PMID: 37184128 PMCID: PMC10358198 DOI: 10.1002/cam4.6086] [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: 12/23/2022] [Revised: 05/01/2023] [Accepted: 05/04/2023] [Indexed: 05/16/2023] Open
Abstract
BACKGROUND Pegylated liposomal doxorubicin (PLD), an anthracycline agent, is widely used as a treatment option for platinum-refractory/resistant epithelial ovarian cancer (EOC). Although only a subset of patients with platinum-refractory/resistant EOC derive benefit from PLD, predictive biomarkers for patients who will respond to the drug have not yet been established. Here, we evaluated the relationship between adipose tissue status and PLD efficacy in patients with platinum-refractory/resistant EOC. METHODS Patients with platinum-refractory/resistant EOC who were treated with single-agent PLD were included in this retrospective cohort study. Adipose tissue areas including visceral adipose tissue area (VATA), subcutaneous adipose tissue area (SATA), and visceral to subcutaneous adipose tissue area ratio (VSR) were calculated prior to the initiation of PLD using computed tomography images. The associations of adipose tissue areas with objective response rate (ORR) and patient survival were evaluated. RESULTS Forty-four patients with platinum-refractory/resistant EOC who received single-agent PLD were included. Subjects were categorized into high and low groups according to the median VATA, SATA, and VSR values, and body mass index (BMI). The ORR of PLD was significantly lower in the VSR-high group than in the VSR-low group (p = 0.0089). Patients in the high VSR group showed significantly shorter progression-free survival (PFS) compared with patients in the low VSR group (median, 4.0 vs. 8.5 months; p = 0.020). In the multivariable analysis, high VSR was a significant prognostic factor for shorter PFS (hazard ratio, 2.07; 95% confidence interval, 1.05-4.19; p = 0.035). VATA, SATA, and BMI showed no significant association with ORR and survival of patients who received PLD. CONCLUSIONS High VSR is associated with lower ORR and shorter PFS in patients with platinum-refractory/resistant EOC who received single-agent PLD. VSR is a robust predictive biomarker for the efficacy of PLD.
Collapse
Affiliation(s)
- Hiroyuki Yoshida
- Department of Gynecologic Oncology, Saitama Medical University International Medical Center, Hidaka, Saitama, Japan
| | - Keiichi Fujiwara
- Department of Gynecologic Oncology, Saitama Medical University International Medical Center, Hidaka, Saitama, Japan
| |
Collapse
|
|
21
|
Hueso L, Marques P, Morant B, Gonzalez-Navarro H, Ortega J, Real JT, Sanz MJ, Piqueras L. CCL17 and CCL22 chemokines are upregulated in human obesity and play a role in vascular dysfunction. Front Endocrinol (Lausanne) 2023; 14:1154158. [PMID: 37124725 PMCID: PMC10130371 DOI: 10.3389/fendo.2023.1154158] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Accepted: 03/27/2023] [Indexed: 05/02/2023] Open
Abstract
Background/Aims Chemokines are known to play critical roles mediating inflammation in many pathophysiological processes. The aim of this study was to investigate the role of chemokine receptor CCR4 and its ligands CCL17 and CCL22 in human morbid obesity. Methods Circulating levels of CCL17 and CCL22 were measured in 60 morbidly obese patients (mean age, 45 ± 1 years; body mass index/BMI, 44 ± 1 kg/m2) who had undergone bariatric bypass surgery, and 20 control subjects. Paired subcutaneous (SCAT) and visceral adipose tissue (VCAT) from patients were analysed to measure expression of CCR4 and its ligands by RT-PCR, western blot and immunohistochemical analysis. The effects of CCR4 neutralization ex vivo on leukocyte-endothelial cells were also evaluated. Results Compared with controls, morbidly obese patients presented higher circulating levels of CCL17 (p=0.029) and CCL22 (p<0.001) and this increase was positively correlated with BMI (p=0.013 and p=0.0016), and HOMA-IR Index (p=0.042 and p< 0.001). Upregulation of CCR4, CCL17 and CCL22 expression was detected in VCAT in comparison with SCAT (p<0.05). Using the parallel-plate flow chamber model, blockade of endothelial CCR4 function with the neutralizing antibody anti-CCR4 in morbidly obese patients significantly reduced leucocyte adhesiveness to dysfunctional endothelium, a key event in atherogenesis. Additionally, CCL17 and CCL22 increased activation of the ERK1/2 mitogen-activated protein kinase signalling pathway in human aortic endothelial cells, which was significantly reduced by CCR4 inhibition (p=0.016 and p<0.05). Conclusion Based on these findings, pharmacological modulation of the CCR4 axis could represent a new therapeutic approach to prevent adipose tissue dysfunction in obesity.
Collapse
Affiliation(s)
- Luisa Hueso
- INCLIVA Biomedical Research Institute, Valencia, Spain
| | | | - Brenda Morant
- INCLIVA Biomedical Research Institute, Valencia, Spain
| | - Herminia Gonzalez-Navarro
- INCLIVA Biomedical Research Institute, Valencia, Spain
- Department of Biochemistry, University of Valencia, Valencia, Spain
- CIBERDEM: Diabetes and Associated Metabolic Diseases Networking Biomedical Research- Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - Joaquin Ortega
- Surgery Service, University Clinic Hospital of Valencia, Valencia, Spain
- Department of Surgery, University of Valencia, Valencia, Spain
| | - José T. Real
- INCLIVA Biomedical Research Institute, Valencia, Spain
- CIBERDEM: Diabetes and Associated Metabolic Diseases Networking Biomedical Research- Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Endocrinology and Nutrition Service, University Clinic Hospital of Valencia, Valencia, Spain
- *Correspondence: Laura Piqueras, ; María J Sanz, ; José T. Real,
| | - María J Sanz
- INCLIVA Biomedical Research Institute, Valencia, Spain
- CIBERDEM: Diabetes and Associated Metabolic Diseases Networking Biomedical Research- Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Department of Pharmacology, University of Valencia, Valencia, Spain
- *Correspondence: Laura Piqueras, ; María J Sanz, ; José T. Real,
| | - Laura Piqueras
- INCLIVA Biomedical Research Institute, Valencia, Spain
- CIBERDEM: Diabetes and Associated Metabolic Diseases Networking Biomedical Research- Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Department of Pharmacology, University of Valencia, Valencia, Spain
- *Correspondence: Laura Piqueras, ; María J Sanz, ; José T. Real,
| |
Collapse
|
|
22
|
Wahb AMSE, Elsaid NBA, Abouzouna ZS, Habieb MSE, Arafat ESE. Vascular endothelial growth factor C gene expression and its serum level as potential biomarkers for obesity in Egyptian children. GENE REPORTS 2022. [DOI: 10.1016/j.genrep.2022.101670] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
|
|
23
|
Mokgalaboni K, Phoswa W. Cross-link between type 2 diabetes mellitus and iron deficiency anemia. A mini-review. CLINICAL NUTRITION OPEN SCIENCE 2022. [DOI: 10.1016/j.nutos.2022.08.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022] Open
|
|
24
|
Obesity and cancer-extracellular matrix, angiogenesis, and adrenergic signaling as unusual suspects linking the two diseases. Cancer Metastasis Rev 2022; 41:517-547. [PMID: 36074318 PMCID: PMC9470659 DOI: 10.1007/s10555-022-10058-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2022] [Accepted: 07/29/2022] [Indexed: 12/24/2022]
Abstract
Obesity is an established risk factor for several human cancers. Given the association between excess body weight and cancer, the increasing rates of obesity worldwide are worrisome. A variety of obesity-related factors has been implicated in cancer initiation, progression, and response to therapy. These factors include circulating nutritional factors, hormones, and cytokines, causing hyperinsulinemia, inflammation, and adipose tissue dysfunction. The impact of these conditions on cancer development and progression has been the focus of extensive literature. In this review, we concentrate on processes that can link obesity and cancer, and which provide a novel perspective: extracellular matrix remodeling, angiogenesis, and adrenergic signaling. We describe molecular mechanisms involved in these processes, which represent putative targets for intervention. Liver, pancreas, and breast cancers were chosen as exemplary disease models. In view of the expanding epidemic of obesity, a better understanding of the tumorigenic process in obese individuals might lead to more effective treatments and preventive measures.
Collapse
|
|
25
|
Pamuk F, Kantarci A. Inflammation as a link between periodontal disease and obesity. Periodontol 2000 2022; 90:186-196. [PMID: 35916870 DOI: 10.1111/prd.12457] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Nutrition plays a critical role in the homeostatic balance, maintenance of health, and longevity. There is a close link between inflammatory diseases and nutritional health. Obesity is a severe pathological process with grave implications on several organ systems and disease processes, including type 2 diabetes, cardiovascular disease, osteoarthritis, and rheumatoid arthritis. The impact of obesity on periodontal inflammation has not been fully understood; the association between nutritional balance and periodontal inflammation is much less explored. This review is focused on the potential mechanistic links between periodontal diseases and obesity and common inflammatory activity pathways that can be pharmacologically targeted.
Collapse
Affiliation(s)
- Ferda Pamuk
- Forsyth Institute, Cambridge, Massachusetts, USA.,Department of Oral Health Sciences, University of Leuven (KU Leuven), Leuven, Belgium
| | | |
Collapse
|
|
26
|
Parente EB, Harjutsalo V, Forsblom C, Groop PH. Waist-Height Ratio and the Risk of Severe Diabetic Eye Disease in Type 1 Diabetes: A 15-Year Cohort Study. J Clin Endocrinol Metab 2022; 107:e653-e662. [PMID: 34508598 PMCID: PMC8764342 DOI: 10.1210/clinem/dgab671] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Indexed: 11/19/2022]
Abstract
CONTEXT Obesity prevalence has increased in type 1 diabetes (T1D). However, the relationship between body composition and severe diabetic eye disease (SDED) is unknown. OBJECTIVE To investigate the associations between body composition and SDED in adults with T1D. METHODS From 5401 adults with T1D in the Finnish Diabetic Nephropathy Study, we assessed 3468, and 437 underwent dual-energy X-ray absorptiometry for body composition analysis. The composite outcome was SDED, defined as proliferative retinopathy, laser treatment, antivascular endothelial growth factor treatment, diabetic maculopathy, vitreous hemorrhage, and vitrectomy. Logistic regression analysis evaluated the associations between body composition and SDED. Multivariable Cox regression analysis assessed the associations between the anthropometric measures and SDED. Subgroup analysis was performed by stages of albuminuria. The relevance ranking of each variable was based on the z statistic. RESULTS During a median follow-up of 14.5 (interquartile range 7.8-17.5) years, 886 SDED events occurred. Visceral/android fat ratio was associated with SDED [odds ratio (OR) 1.40, z = 3.13], as well as the percentages of visceral (OR 1.80, z = 2.45) and android fat (OR 1.28, z = 2.08) but not the total body fat percentage. Waist-height ratio (WHtR) showed the strongest association with the SDED risk [hazard ratio (HR) = 1.28, z = 3.73], followed by the waist (HR 1.01, z = 3.03), body mass index (HR 1.03, z = 2.33), and waist-hip ratio (HR 1.15, z = 2.22). The results were similar in normo- and microalbuminuria but not significant in macroalbuminuria. A WHtR ≥ 0.5 increased the SDED risk by 28% at the normo- and microalbuminuria stages. CONCLUSIONS WHtR, a hallmark of central obesity, is associated with SDED in individuals with T1D.
Collapse
Affiliation(s)
- Erika B Parente
- Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland
- Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland
- Department of Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Valma Harjutsalo
- Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland
- Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland
- Department of Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
- National Institute for Health and Welfare, Helsinki, Finland
| | - Carol Forsblom
- Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland
- Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland
- Department of Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Per-Henrik Groop
- Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland
- Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland
- Department of Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
- Department of Diabetes, Central Clinical School, Monash University, Melbourne, Victoria, Australia
- Correspondence: Per-Henrik Groop, MD, DMSc, Folkhälsan Research Center, Biomedicum Helsinki, FIN-00014 University of Helsinki, Finland. E-mail:
| |
Collapse
|
|
27
|
Wambui D, Mohamed S, Asiki G. Prevalence of and factors associated with high atherogenic index among adults in Nairobi urban informal settlements: The AWI-Gen study. PLOS GLOBAL PUBLIC HEALTH 2022; 2:e0000224. [PMID: 36962293 PMCID: PMC10021160 DOI: 10.1371/journal.pgph.0000224] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/12/2021] [Accepted: 05/09/2022] [Indexed: 11/19/2022]
Abstract
Dyslipidemia is an important cardiovascular disease predictor. Atherogenic index of plasma (AIP), a ratio of triglycerides (TG) to high density lipoprotein (HDL) cholesterol has been deemed to be more informative as a cardiovascular disease predictor compared to using any single predictor. The aim of this study was to explore the factors associated with elevated atherogenic index among people living in low-income urban areas of Nairobi, Kenya. Data used in this study were obtained from a cross-sectional population-based study with 2,003 participants conducted in Nairobi as part of the Africa Wits-INDEPTH Partnership for Genomic Research, AWI-Gen). Sociodemographic, behavioral, and clinical characteristics were collected from the participants. AIP was derived from the log of TG/HDL cholesterol and categorized into low risk (AIP<0.1), intermediate risk (AIP = 0.1-0.24) and high risk (AIP >0.24). Fifty-four percent (54%) of the study participants were women and the mean age of participants enrolled in this study was 48.8 years. Twenty-nine percent (29%) of study participants had high or medium atherogenic risk. Men, HIV patients, individuals with self-reported uncontrolled diabetes and obese individuals were at higher atherogenic risk. We have identified modifiable risk factors which can be addressed to reduce dyslipidemia in this population. Longitudinal studies may help to precisely determine how these factors relate with cardiovascular diseases.
Collapse
Affiliation(s)
- David Wambui
- Department of Public Health, East Carolina University, Greenville, North Carolina, United States of America
| | - Shukri Mohamed
- Health and Systems for Health Unit, African Population and Health Research Center (APHRC), Nairobi, Kenya
| | - Gershim Asiki
- Health and Systems for Health Unit, African Population and Health Research Center (APHRC), Nairobi, Kenya
- Department of Women's and Children's Health, Karolinska Institute, Stockholm, Sweden
| |
Collapse
|
|
28
|
Su Z, Wu Z, Liang X, Xie M, Xie J, Li H, Wang X, Jiang F. Diabetic retinopathy risk in patients with unhealthy lifestyle: A Mendelian randomization study. Front Endocrinol (Lausanne) 2022; 13:1087965. [PMID: 36733810 PMCID: PMC9887126 DOI: 10.3389/fendo.2022.1087965] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2022] [Accepted: 12/28/2022] [Indexed: 01/19/2023] Open
Abstract
PURPOSE This study aimed to investigate the causal association between unhealthy lifestyle factors and diabetic retinopathy (DR) risk and to determine better interventions targeting these modifiable unhealthy factors. DESIGN Two-sample Mendelian randomization (MR) analysis was performed in this study. The inverse variance-weighted method was used as the primary method. METHOD Our study included 687 single-nucleotide polymorphisms associated with unhealthy lifestyle factors as instrumental variables. Aggregated data on individual-level genetic information were obtained from the corresponding studies and consortia. A total of 292,622,3 cases and 739,241,18 variants from four large consortia (MRC Integrative Epidemiology Unit [MRC-IEU], Genetic Investigation of Anthropometric Traits [GIANT], GWAS & Sequencing Consortium of Alcohol and Nicotine Use [GSCAN], and Neale Lab) were included. RESULT In the MR analysis, a higher body mass index (BMI) (odds ratio [OR], 95% confidence interval [CI] = 1.42, 1.30-1.54; P < 0.001] and cigarettes per day (OR, 95% CI = 1.16, 1.05-1.28; P = 0.003) were genetically predicted to be causally associated with an increased risk of DR, while patients with higher hip circumference (HC) had a lower risk of DR (OR, 95% CI = 0.85, 0.76-0.95; P = 0.004). In the analysis of subtypes of DR, the results of BMI and HC were similar to those of DR, whereas cigarettes per day were only related to proliferative DR (PDR) (OR, 95% CI = 1.18, 1.04-1.33; P = 0.009). In the MR-PRESSO analysis, a higher waist-to-hip ratio (WHR) was a risk factor for DR and PDR (OR, 95% CI = 1.24, 1.02-1.50, P = 0.041; OR, 95% CI = 1.32, 1.01-1.73, P = 0.049) after removing the outliers. Furthermore, no pleiotropy was observed in these exposures. CONCLUSION Our findings suggest that higher BMI, WHR, and smoking are likely to be causal factors in the development of DR, whereas genetically higher HC is associated with a lower risk of DR, providing insights into a better understanding of the etiology and prevention of DR.
Collapse
Affiliation(s)
- Zixuan Su
- Department of Ophthalmology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Zhixin Wu
- Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xueqing Liang
- Department of Biostatistics, School of Public Health, Southern Medical University, Guangzhou, China
| | - Meng Xie
- Department of Ophthalmology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jia Xie
- Department of Ophthalmology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Huiqing Li
- Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xinghua Wang
- Department of Ophthalmology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- *Correspondence: Fagang Jiang, ; Xinghua Wang,
| | - Fagang Jiang
- Department of Ophthalmology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- *Correspondence: Fagang Jiang, ; Xinghua Wang,
| |
Collapse
|
|
29
|
Du Y, Yang W, Liu H, Qin C, Tang X, Xu T. Perirenal Fat as a New Independent Prognostic Factor in Patients With Surgically Treated Clear Cell Renal Cell Carcinoma. Clin Genitourin Cancer 2021; 20:e75-e80. [PMID: 34802967 DOI: 10.1016/j.clgc.2021.10.006] [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: 05/03/2021] [Revised: 10/07/2021] [Accepted: 10/16/2021] [Indexed: 11/18/2022]
Abstract
INTRODUCTION Recently increasing evidence has suggested that obesity is associated with the development and prognosis of renal cell carcinoma. The aim of the study was to investigate the association between different obesity measurements and overall survival in patients with surgically treated clear cell renal cell carcinoma. PATIENTS AND METHODS The data of 342 consecutive patients who underwent radical or partial nephrectomy at Peking University People's Hospital from January 2009 to November 2014 were retrospectively reviewed. Median follow-up was 82 months. The association between different obesity measurements and overall survival was evaluated using the Kaplan-Meier method and Cox regression models. RESULTS In univariate Cox regression analyses, perirenal fat accumulation was significantly associated with overall survival (HR: 2.271; 95% CI: 1.311-3.935; P = .003), as well as age, sex, clinical manifestation, surgical option, tumor size, and grade. The other obesity measurements, including body mass index, waist circumference, total adipose tissue, visceral adipose tissue, and percentage of visceral adipose tissue, were not assessed as prognostic indicators of overall survival in this study (P > .05). After adjusting for age, sex, clinical manifestation, surgical option, tumor size, T stage, and tumor grade, perirenal fat accumulation was still identified as an independent predictor of overall survival (HR: 2.264; 95% CI: 1.305-3.926; P == .004). The results of Kaplan-Meier model also revealing that patients with higher percentage of perirenal fat showed poorer overall survival (P == .003). CONCLUSION Higher percentage of perirenal adipose tissue is independently associated with increased mortality risk in surgically treated clear cell renal cell carcinoma.
Collapse
Affiliation(s)
- Yiqing Du
- Department of Urology, Peking University People's Hospital, Beijing 100044, China
| | - Wenbo Yang
- Department of Urology, Peking University People's Hospital, Beijing 100044, China
| | - Huixin Liu
- Department of Clinical Epidemiology, Peking University People's Hospital, Beijing 100044, China
| | - Caipeng Qin
- Department of Urology, Peking University People's Hospital, Beijing 100044, China
| | - Xu Tang
- Department of Urology, Peking University People's Hospital, Beijing 100044, China
| | - Tao Xu
- Department of Urology, Peking University People's Hospital, Beijing 100044, China.
| |
Collapse
|
|
30
|
Okubo S, Shindoh J, Kobayashi Y, Umino R, Akabane M, Kojima K, Hashimoto M. Adipose Tissue Distribution Predicts Prognosis of Cirrhotic Patients Undergoing Hepatectomy for Hepatocellular Carcinoma. Ann Surg Oncol 2021; 28:6738-6746. [PMID: 33554286 DOI: 10.1245/s10434-021-09658-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2020] [Accepted: 01/09/2021] [Indexed: 12/30/2022]
Abstract
BACKGROUND Body composition data are reportedly correlated with patient prognosis for various cancers. However, little is known about the prognostic impact of adipose tissue distribution among patients with hepatocellular carcinoma (HCC). METHODS Data for 181 consecutive cirrhotic patients who underwent hepatectomy for HCC were retrospectively reviewed. The clinical significance of the visceral-to-subcutaneous adipose tissue ratio (VSR) was investigated through analysis of short- and long-term surgical outcomes. RESULTS Of the 181 patients, 60 (33%) were classified as the high-VSR group and 121 (67%) as the low-VSR group. Although VSR was not correlated with a risk of postoperative morbidity, multivariate analysis confirmed that a higher VSR was significantly correlated with a shorter time to interventional failure (hazard ratio [HR] 2.24; P = 0.008) and overall survival (HR 2.65; P = 0.001) independently of American Joint Committed on Cancer stage or preoperative nutritional status. Analysis of the recurrence patterns showed that the proportion of unresectable recurrence at the initial recurrence event was significantly higher in the high-VSR group (39% vs. 18%; P = 0.025). The yearly transition probabilities, defined by a Markov model from postoperative R0 status to advanced disease or death (7.6% vs. 1.5%, P < 0.001) and early recurrence stage to advanced disease or death (15.4% vs. 2.8%, P = 0.004), were higher in the high-VSR group, suggesting that patients with a higher VSR are vulnerable to disease progression. CONCLUSION A high VSR was found to be an independent predictor of disease progression and poor prognosis for HCC patients with underlying liver cirrhosis having resection for HCC.
Collapse
Affiliation(s)
- Satoshi Okubo
- Hepato-Biliary-Pancreatic Surgery Division, Department of Gastroenterological surgery, Toranomon Hospital, Minatoku, Tokyo, Japan
| | - Junichi Shindoh
- Hepato-Biliary-Pancreatic Surgery Division, Department of Gastroenterological surgery, Toranomon Hospital, Minatoku, Tokyo, Japan.
- Okinaka Memorial Institute for Medical Disease, Tokyo, Japan.
| | - Yuta Kobayashi
- Hepato-Biliary-Pancreatic Surgery Division, Department of Gastroenterological surgery, Toranomon Hospital, Minatoku, Tokyo, Japan
| | - Ryosuke Umino
- Hepato-Biliary-Pancreatic Surgery Division, Department of Gastroenterological surgery, Toranomon Hospital, Minatoku, Tokyo, Japan
| | - Miho Akabane
- Hepato-Biliary-Pancreatic Surgery Division, Department of Gastroenterological surgery, Toranomon Hospital, Minatoku, Tokyo, Japan
| | - Kazutaka Kojima
- Hepato-Biliary-Pancreatic Surgery Division, Department of Gastroenterological surgery, Toranomon Hospital, Minatoku, Tokyo, Japan
| | - Masaji Hashimoto
- Hepato-Biliary-Pancreatic Surgery Division, Department of Gastroenterological surgery, Toranomon Hospital, Minatoku, Tokyo, Japan
| |
Collapse
|
|
31
|
Ribatti D, Annese T, Tamma R. Adipocytes, mast cells and angiogenesis. ROMANIAN JOURNAL OF MORPHOLOGY AND EMBRYOLOGY 2021; 61:1051-1056. [PMID: 34171054 PMCID: PMC8343648 DOI: 10.47162/rjme.61.4.07] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/05/2022]
Abstract
Healthy adipose tissue contains a wide variety of innate and adaptive immune cells, including macrophages, dendritic cells, mast cells, eosinophils, neutrophils, and lymphocytes. Numerous signaling molecules in the adipose microenvironment can positively or negatively modulate angiogenic processes, regulate the interaction between the vascular system and adipocytes, and participate in tumor progression. Mast cells are involved in the new formation or metabolism of fat, are present in abundant quantities in fatty tissue, among fat cells, and a number of mediators released from mast cells play a role in adipogenesis. Moreover, mast cells produce several pro-angiogenic factors and are involved in tumor angiogenesis. In this context, the angiogenic effect might be amplified when the adipocytes and mast cells act in concert, and treatment of adipose tissue- and mast cell-associated cancers with anti-angiogenic drugs may represent an alternative or adjuvant strategy for the treatment of these tumors.
Collapse
Affiliation(s)
- Domenico Ribatti
- Department of Basic Medical Sciences, Neurosciences and Sensory Organs, University of Bari Medical School, Bari, Italy;
| | | | | |
Collapse
|
|
32
|
Garay-Sevilla ME, Gomez-Ojeda A, González I, Luévano-Contreras C, Rojas A. Contribution of RAGE axis activation to the association between metabolic syndrome and cancer. Mol Cell Biochem 2021; 476:1555-1573. [PMID: 33398664 DOI: 10.1007/s11010-020-04022-z] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2020] [Accepted: 12/11/2020] [Indexed: 02/07/2023]
Abstract
Far beyond the compelling proofs supporting that the metabolic syndrome represents a risk factor for diabetes and cardiovascular diseases, a growing body of evidence suggests that it is also a risk factor for different types of cancer. However, the involved molecular mechanisms underlying this association are not fully understood, and they have been mainly focused on the individual contributions of each component of the metabolic syndrome such as obesity, hyperglycemia, and high blood pressure to the development of cancer. The Receptor for Advanced Glycation End-products (RAGE) axis activation has emerged as an important contributor to the pathophysiology of many clinical entities, by fueling a chronic inflammatory milieu, and thus supporting an optimal microenvironment to promote tumor growth and progression. In the present review, we intend to highlight that RAGE axis activation is a crosswise element on the potential mechanistic contributions of some relevant components of metabolic syndrome into the association with cancer.
Collapse
Affiliation(s)
- Ma Eugenia Garay-Sevilla
- Department of Medical Science, Division of Health Science, University of Guanajuato, Campus León, Guanajuato, Mexico
| | - Armando Gomez-Ojeda
- Department of Medical Science, Division of Health Science, University of Guanajuato, Campus León, Guanajuato, Mexico
| | - Ileana González
- Biomedical Research Labs, Medicine Faculty, Catholic University of Maule, Talca, Chile
| | - Claudia Luévano-Contreras
- Department of Medical Science, Division of Health Science, University of Guanajuato, Campus León, Guanajuato, Mexico
| | - Armando Rojas
- Biomedical Research Labs, Medicine Faculty, Catholic University of Maule, Talca, Chile.
| |
Collapse
|
|
33
|
Clinical and genomic characteristics of metabolic syndrome in colorectal cancer. Aging (Albany NY) 2021; 13:5442-5460. [PMID: 33582655 PMCID: PMC7950286 DOI: 10.18632/aging.202474] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2020] [Accepted: 11/30/2020] [Indexed: 12/27/2022]
Abstract
Metabolic syndrome (MetS) is characterized by a group of metabolic disturbances which leads to the enhanced risk of cancer development. Elucidating the mechanisms between these two pathologies is essential to identify the potential therapeutic molecular targets for colorectal cancer (CRC). 716 colorectal patients from the First and Second Affiliated Hospital of Wenzhou Medical University were involved in our study and metabolic disorders were proven to increase the risk of CRC. The prognostic value of the MetS factors was analyzed using the Cox regression model and a clinical MetS-based nomogram was established. Then by using multi-omics techniques, the distinct molecular mechanism of MetS genes in CRC was firstly systematically characterized. Strikingly, MetS genes were found to be highly correlated with the effectiveness of targeted chemotherapy administration, especially for mTOR and VEGFR pathways. Our results further demonstrated that overexpression of MetS core gene IL6 would promote the malignancy of CRC, which was highly dependent on mTOR-S6K signaling. In conclusion, we comprehensively explored the clinical value and molecular mechanism of MetS in the progression of CRC, which may serve as a candidate option for cancer management and therapy in the future.
Collapse
|
|
34
|
Onozaki A, Nagayama D, Azuma N, Sugai K, Shitara E, Sakai T, Masai M, Shirai K, Tatsuno I. Relation of Maximum Lifetime Body Mass Index with Age at Hemodialysis Initiation and Vascular Complications in Japan. Obes Facts 2021; 14:550-558. [PMID: 34515199 PMCID: PMC8546452 DOI: 10.1159/000518049] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Accepted: 06/16/2021] [Indexed: 01/02/2023] Open
Abstract
OBJECTIVE The aim of this study was to investigate the association of the maximum lifetime body mass index (max BMI) with hemodialysis initiation and comorbidities in Japanese hemodialysis patients. METHODS In a retrospective cross-sectional study on 724 hemodialysis patients, max BMI, age at hemodialysis initiation, and comorbidities including sleep apnea syndrome, cerebro-cardiovascular diseases, and proliferative diabetic retinopathy (PDR) were analyzed. Early hemodialysis initiation was defined as age <50 years. RESULT Diabetes patients showed a higher max BMI and prevalence of atherosclerotic diseases than nondiabetes patients, despite almost the same age at hemodialysis initiation. Patients with early hemodialysis initiation showed higher male ratio, prevalence of PDR, and max BMI than those with later initiation, despite almost equal prevalence of diabetes. Receiver-operating characteristic curve analysis determined a max BMI of 28.4 kg/m2 as a reliable cutoff value for predicting early hemodialysis initiation, and this parameter was identified as an independent predictor of early hemodialysis initiation using bivariate logistic regression analysis. Vitrectomy for PDR also tended to contribute independently to early hemodialysis initiation. CONCLUSION A high max BMI contributed to early hemodialysis initiation independent of diabetes. Furthermore, PDR was associated with a high max BMI and early hemodialysis initiation. These results suggest that weight reduction in young chronic kidney disease patients with obesity may prevent hemodialysis and blindness.
Collapse
Affiliation(s)
- Akira Onozaki
- Internal Medicine, Tokatsu Clinic Hospital, Chiba, Japan
| | - Daiji Nagayama
- Internal Medicine, Nagayama Clinic, Tochigi, Japan
- Center of Diabetes, Endocrine and Metabolism, Toho University Sakura Medical Center, Chiba, Japan
- *Daiji Nagayama,
| | - Nakanobu Azuma
- Internal Medicine, Tokatsu Clinic Hospital, Chiba, Japan
| | - Keita Sugai
- Nutrition Management Division, Mihama Hospital, Chiba, Japan
| | - Etsuko Shitara
- Nutrition Management Division, Mihama Hospital, Chiba, Japan
| | | | | | - Kohji Shirai
- Internal Medicine, Mihama Hospital, Chiba, Japan
| | - Ichiro Tatsuno
- Center of Diabetes, Endocrine and Metabolism, Toho University Sakura Medical Center, Chiba, Japan
- Chiba Prefectural University of Health Sciences, Chiba, Japan
| |
Collapse
|
|
35
|
Ghazizadeh H, Esmaily H, Sharifan P, Parizadeh SMR, Ferns GA, Rastgar-Moghadam A, Khedmatgozar H, Ghayour-Mobarhan M, Avan A. Interaction between a genetic variant in vascular endothelial growth factor with dietary intakes in association with the main factors of metabolic syndrome. GENE REPORTS 2020. [DOI: 10.1016/j.genrep.2020.100813] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
|
|
36
|
Severina AS, Shestakova MV. [Angiogenesis system, as a part of endothelial dysfunction in patients with diabetes mellitus type 2: relationship with obesity]. TERAPEVT ARKH 2020; 92:23-28. [PMID: 33346475 DOI: 10.26442/00403660.2020.10.000781] [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: 11/23/2020] [Accepted: 11/23/2020] [Indexed: 11/22/2022]
Abstract
AIM To investigate parameters of angiogenesis system in patients with diabetes mellitus and their relationship with obesity. MATERIALS AND METHODS 104 patients with diabetes mellitus type 2 were included in the study. Patients were divided in 2 groups: Obesity+ (body mass index30 kg/m2;n=63) and Obesity- (body mass index 30 kg/m2;n=41). In all patients was performed clinico-diagnostical examination. mRNA expression levels of vascular endothelial growth factor (VEGF), its receptors flt-1 (fms-like tyrosine kinase 1), KDR (human kinase insert domain receptor) were determined in blood mononuclear cells. RESULTS There were no statistically significant differences in investigated parameters between study groups. mRNA expression level of VEGF was slightly lower in men compared to women: 0.19 (0.14; 0.32)vs0.28 (0.12; 0.4) respectively,р=0.2236. MRNA expression level of flt-1 was lower in men compared to women: 0.14 (0.04; 0.3)vs0.25 (0.12; 0.38),р=0.0321 (statistically significant). We found statistically significant correlations of mRNA expression level of VEGF with mRNA expression level of flt-1 and KDR. Also we found strong positive correlations of BMI and mRNA expression levels VEGF, flt-1, KDR (r=0.86107,r=0.86125,r=0.86112, respectively,p0.001). CONCLUSION Results of the study displayed relationship of obesity and angiogenesis system condition in patients with diabetes mellitus type 2. Further investigations are perspective for the future as a way to new therapeutical approach of obesity and its complications treatment.
Collapse
|
|
37
|
The interaction between dietary inflammatory index and 6 P21 rs2010963 gene variants in metabolic syndrome. Eat Weight Disord 2020; 25:1049-1060. [PMID: 31197703 DOI: 10.1007/s40519-019-00729-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2019] [Accepted: 06/05/2019] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND The Vascular endothelial growth factor (VEGF) regulates endothelial cell proliferation, migration and angiogenesis, promotes vascular and capillary permeability and also is involved in inflammation. VEGF gene has been suggested to play an important role in the pathogenesis of metabolic syndrome. The aim of this study was to investigate the association between inflammatory potential of a diet and + 405 VEGF C/G (rs2010963) polymorphism and metabolic components in patients with metabolic syndrome. METHODS One hundred fifty patients with metabolic syndrome and fifty healthy individuals were enrolled. A semi-quantitative food-frequency questionnaire (FFQ) was used for dietary assessments and dietary inflammatory index (DII) calculation. Biochemical assays including fasting serum glucose (FSG), serum insulin, matrix metalloproteinase-3 (MMP-3), liver enzymes and lipid profile were measured. Polymerase chain reaction-restriction fragments length polymorphism (PCR-RFLP) method was used for the determination of gene polymorphism. RESULTS In the current study, patients with metabolic syndrome had higher serum low density lipoprotein (LDL) and lower high density lipoprotein (HDL) concentrations compared with healthy subjects. Patients with lower DII quartiles and lower inflammatory potential of the diet had lower waist to hip ratio (WHR) and lower diastolic blood pressure (DBP) compared with patients in higher DII quartiles (P < 0.05). Moreover, patients and healthy subjects in second quartile of DII had significantly higher aspartate aminotransferase (AST) and alanine aminotransferase (ALT) concentrations compared with subjects in the first quartile; also healthy subjects in third quartile had significantly higher triglyceride (TG) and total cholesterol (TC) concentrations compared with subjects in second quartile (P < 0.05). Among different genotypes of 6 P21 rs2010963 gene variants in patients with metabolic syndrome, CC genotype indicated the highest DII compared with other genotypes (P < 0.05). CONCLUSION The current study revealed the association between DII and metabolic risk factors of metabolic syndrome. LEVEL OF EVIDENCE Level III, case-control analytic study.
Collapse
|
|
38
|
Zhai T, Wu X, Zhang N, Huang X, Zhan Q. Inflammatory risk factors for hypertriglyceridemia in patients with severe influenza. J Int Med Res 2020; 48:300060520918058. [PMID: 32776792 PMCID: PMC7871290 DOI: 10.1177/0300060520918058] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2019] [Accepted: 03/09/2020] [Indexed: 01/01/2023] Open
Abstract
OBJECTIVE Inflammation and viral infections can induce significant changes in lipid metabolism. Hypertriglyceridemia (HTG) often occurs secondary to obesity, which is an independent risk factor for influenza virus infection. However, the inflammatory risk factors contributing to HTG in patients with severe influenza have yet to be elucidated. MATERIALS AND METHODS Plasma and bronchoalveolar lavage fluid (BALF) samples were collected from 33 patients with severe influenza (n = 26 control patients with normal serum triglyceride levels and n = 7 HTG patients with serum triglycerides >2.3 mM). Levels of 45 putative inflammatory risk factors were quantitated using a commercial enzyme-linked immunosorbent assay kit. RESULTS Plasma levels of interferon (IFN)-γ, interleukin (IL)-18, IL-1 receptor antagonist (IL-1RA), monocyte chemoattractant protein-1, macrophage inflammatory protein-1α, hepatocyte growth factor, stem cell factor, and vascular endothelial growth factor A were significantly higher in HTG patients compared with control patients. BALF samples from HTG patients contained significantly higher levels of IL-1RA and lower levels of IFN-γ-inducible protein-10. CONCLUSION HTG in patients with severe influenza is associated with alterations in several inflammatory risk factors. Our results provide new insights that may enable more effective clinical management of severe influenza combined with HCT.
Collapse
Affiliation(s)
- Tianshu Zhai
- Center for Respiratory Diseases, Department of
Pulmonary and Critical Care Medicine,
China-Japan
Friendship Hospital, Beijing,
China
| | - Xiaojing Wu
- Center for Respiratory Diseases, Department of
Pulmonary and Critical Care Medicine,
China-Japan
Friendship Hospital, Beijing,
China
| | - Nannan Zhang
- Center for Respiratory Diseases, Department of
Pulmonary and Critical Care Medicine,
China-Japan
Friendship Hospital, Beijing,
China
| | - Xu Huang
- Center for Respiratory Diseases, Department of
Pulmonary and Critical Care Medicine,
China-Japan
Friendship Hospital, Beijing,
China
| | - Qingyuan Zhan
- Center for Respiratory Diseases, Department of
Pulmonary and Critical Care Medicine,
China-Japan
Friendship Hospital, Beijing,
China
| |
Collapse
|
|
39
|
Zhang Y, Ma T, Hu H, Wang J, Zhou S. Serum vascular endothelial growth factor as a biomarker for prognosis of minor ischemic stroke. Clin Neurol Neurosurg 2020; 196:106060. [PMID: 32645625 DOI: 10.1016/j.clineuro.2020.106060] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2020] [Revised: 06/27/2020] [Accepted: 06/30/2020] [Indexed: 01/17/2023]
Abstract
Objectives Although vascular endothelial growth factor (VEGF) is a well-known molecule involved with neuronal survival and angiogenesis. there are no prospective studies directed at evaluating a potential association between serum VEGF and minor ischemic stroke. The goal of this study was to investigate the utility of serum VEGF as an index for assessing the 90-day prognosis of minor ischemic stroke patients. Methods Records of acute minor stroke patients (N = 225) and those of age- and gender-matched healthy control subjects (N = 225) were prospectively reviewed. Clinical, laboratory, and imaging data were evaluated. Serum samples collected from these stroke patients immediately after admission were assessed for VEGF levels and compared with those of control subjects. Results Serum VEGF levels were significantly increased in stroke patients (40.01 ± 16.48 pg/mL) as compared with those of controls (32.98 ± 10.35 pg/mL). No statistically significant differences in serum VEGF levels were obtained among the three stroke subtypes analyzed in this study (large-artery atherosclerosis, small-artery occlusion and other types of brain infarction). Multivariate regression analysis revealed that serum VEGF levels and cerebral artery stenosis ≥ 50 % were independently associated with an unfavorable outcome. Unfavorable outcome rates were significantly greater in stroke patients showing VEGF levels in the upper quartiles of the distribution, and these VEGF levels were found to serve as a significant predictor of unfavorable outcomes in these minor ischemic stroke patients. Conclusion Increased serum VEGF may serve as an independent predictor of an unfavorable outcome in minor ischemic stroke.
Collapse
Affiliation(s)
- Yan Zhang
- Department of Neurology, First Affiliated Hospital of Harbin Medical University, Harbin, Hei Longjiang Province, PR China.
| | - Tong Ma
- Department of Neurology, First Affiliated Hospital of Harbin Medical University, Harbin, Hei Longjiang Province, PR China
| | - Haijie Hu
- Department of Neurology, First Affiliated Hospital of Harbin Medical University, Harbin, Hei Longjiang Province, PR China
| | - Jiakai Wang
- Department of Neurology, First Affiliated Hospital of Harbin Medical University, Harbin, Hei Longjiang Province, PR China
| | - Shanshan Zhou
- Department of Neurology, First Affiliated Hospital of Harbin Medical University, Harbin, Hei Longjiang Province, PR China
| |
Collapse
|
|
40
|
Overweight is associated with better prognosis in metastatic colorectal cancer patients treated with bevacizumab plus FOLFOX chemotherapy. Contemp Oncol (Pozn) 2020; 24:34-41. [PMID: 32514236 PMCID: PMC7265962 DOI: 10.5114/wo.2020.94728] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2020] [Accepted: 03/13/2020] [Indexed: 12/12/2022] Open
Abstract
Introduction Previous studies showed that high and low body mass index (BMI) was associated with worse prognosis in metastatic CRC (mCRC). Whether BMI is a prognostic or predictive factor in mCRC is unclear. We aimed to assess efficacy outcomes according to BMI in patient with metastatic colorectal cancer treated with bevacizumab plus FOLFOX chemotherapy regimen in second-line treatment. Material and methods The analysis of 237 patients with metastatic colorectal cancer treated with bevacizumab plus FOLFOX in the second line (treated from January 2014 to August 2018) in 4 reference oncological centers in Poland. Results The median age of the patients was 65 years (range 34-82). The median overall survival (OS) and progression-free survival (PFS) of the all 237 patient was 14.6 and 8.8 months, respectively. Comparison of obese patient (BMI > 30 kg/m2) vs. overweight patients (BMI ≥ 25 to < 30 kg/m2) vs. normal BMI range patients revealed a significant improvement of median OS (17.5 vs. 14.3 vs. 13.1 months, p = 0.01) and median PFS (9.4 vs. 9.1 vs. 7.3 months, p = 0.03). The Cox hazard model showed that the BMI class is an important risk factor. However, the Cox model also showed that the significance of the BMI class applies only to patients with BMI < 25 kg/m2. This rule applies to both OS and PFS. The regression analysis also confirmed that there is a statistically significant relationship between the length of OS and PFS and the BMI value. Higher BMI was associated with a better prognosis. There were no differences in responses to treatment bevacizumab and FOLFOX chemotherapy and number adverse events according to BMI values. Conclusions Patients with mCRC treated with chemotherapy with bevacizumab in second-line treatment with higher BMI compared with normal weight patients have better prognosis in terms of PFS and OS. In this group, we found no evidence of changes in safety profile depending on BMI. Nevertheless, further large randomized studies are needed to assess the body weight on the effectiveness of chemotherapy in combination with bevacizumab.
Collapse
|
|
41
|
Kataru RP, Park HJ, Baik JE, Li C, Shin J, Mehrara BJ. Regulation of Lymphatic Function in Obesity. Front Physiol 2020; 11:459. [PMID: 32499718 PMCID: PMC7242657 DOI: 10.3389/fphys.2020.00459] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2020] [Accepted: 04/16/2020] [Indexed: 12/15/2022] Open
Abstract
The lymphatic system has many functions, including macromolecules transport, fat absorption, regulation and modulation of adaptive immune responses, clearance of inflammatory cytokines, and cholesterol metabolism. Thus, it is evident that lymphatic function can play a key role in the regulation of a wide array of biologic phenomenon, and that physiologic changes that alter lymphatic function may have profound pathologic effects. Recent studies have shown that obesity can markedly impair lymphatic function. Obesity-induced pathologic changes in the lymphatic system result, at least in part, from the accumulation of inflammatory cells around lymphatic vessel leading to impaired lymphatic collecting vessel pumping capacity, leaky initial and collecting lymphatics, alterations in lymphatic endothelial cell (LEC) gene expression, and degradation of junctional proteins. These changes are important since impaired lymphatic function in obesity may contribute to the pathology of obesity in other organ systems in a feed-forward manner by increasing low-grade tissue inflammation and the accumulation of inflammatory cytokines. More importantly, recent studies have suggested that interventions that inhibit inflammatory responses, either pharmacologically or by lifestyle modifications such as aerobic exercise and weight loss, improve lymphatic function and metabolic parameters in obese mice. The purpose of this review is to summarize the pathologic effects of obesity on the lymphatic system, the cellular mechanisms that regulate these responses, the effects of impaired lymphatic function on metabolic syndrome in obesity, and the interventions that may improve lymphatic function in obesity.
Collapse
Affiliation(s)
- Raghu P Kataru
- Plastic and Reconstructive Surgery Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, United States
| | - Hyeong Ju Park
- Plastic and Reconstructive Surgery Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, United States
| | - Jung Eun Baik
- Plastic and Reconstructive Surgery Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, United States
| | - Claire Li
- Plastic and Reconstructive Surgery Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, United States
| | - Jinyeon Shin
- Plastic and Reconstructive Surgery Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, United States
| | - Babak J Mehrara
- Plastic and Reconstructive Surgery Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, United States
| |
Collapse
|
|
42
|
Tokunaga R, Nakagawa S, Miyamoto Y, Ohuchi M, Izumi D, Kosumi K, Taki K, Higashi T, Miyata T, Yoshida N, Baba H. The clinical impact of preoperative body composition differs between male and female colorectal cancer patients. Colorectal Dis 2020; 22:62-70. [PMID: 31344314 DOI: 10.1111/codi.14793] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2019] [Accepted: 07/15/2019] [Indexed: 12/18/2022]
Abstract
AIM Patient body composition is an important indicator of metabolic status and is associated with cancer progression. Because body composition varies between men and women, we aimed to examine the difference in clinical impact of preoperative body composition according to sex. METHOD We used an integrated dataset of 559 colorectal cancer (CRC) patients. The association between preoperative body composition indices [body mass index (BMI), visceral to subcutaneous fat area ratio (VSR) and skeletal muscle index (SMI)] and patient outcome, clinicopathological factors and preoperative inflammation and nutritional status was analysed, comparing men and women. RESULTS Preoperative low BMI and low SMI in men was significantly associated with unfavourable overall survival (OS) [BMI: hazard ratio (HR) 2.22, 95% CI 1.28-4.14, P = 0.004; SMI: HR 2.54, 95% CI 1.61-4.07, P < 0.001] and high VSR in women was significantly associated with unfavourable OS (HR 1.79, 95% CI 1.03-3.02, P = 0.040). Additionally, low SMI in men was significantly associated with deeper tumour invasion and greater distant metastasis and high VSR in women was significantly associated with advanced age, right-sided tumour, lower total lymphocyte count and lower albumin levels. Interestingly, low BMI in men was significantly associated with deeper tumour invasion, but also with favourable inflammation and nutritional status (lower C-reactive protein and higher albumin). CONCLUSION The clinical impact of preoperative body composition differed between men and women: SMI in men and VSR in women were good prognosticators. Our findings may provide a novel insight for CRC treatment strategies.
Collapse
Affiliation(s)
- R Tokunaga
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - S Nakagawa
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Y Miyamoto
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - M Ohuchi
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - D Izumi
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - K Kosumi
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - K Taki
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - T Higashi
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - T Miyata
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - N Yoshida
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - H Baba
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| |
Collapse
|
|
43
|
Shepel RN, Drapkina OM. New directions in metabolic syndrome diagnosis: assessment of vascular endothelial growth factor, pentraxin-3 and transforming growth factor beta levels. КАРДИОВАСКУЛЯРНАЯ ТЕРАПИЯ И ПРОФИЛАКТИКА 2019. [DOI: 10.15829/1728-8800-2019-6-57-61] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022] Open
Affiliation(s)
- R. N. Shepel
- National Medical Research Center for Preventive Medicine
| | - O. M. Drapkina
- National Medical Research Center for Preventive Medicine
| |
Collapse
|
|
44
|
Abbasalizad Farhangi M, Vajdi M, Nikniaz L, Nikniaz Z. Interaction between Vascular Endothelial Growth Factor-A (rs2010963) Gene Polymorphisms and Dietary Diversity Score on Cardiovascular Risk Factors in Patients with Metabolic Syndrome. Lifestyle Genom 2019; 13:1-10. [DOI: 10.1159/000503789] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2019] [Accepted: 09/23/2019] [Indexed: 11/19/2022] Open
|
|
45
|
Yildiz M, Bozkurtlar E, Azizy A, Agirbasli M. Immunohistochemical expression of plasminogen activator inhibitor-1 in subcutaneous versus omental adipose tissue in patients after elective abdominal surgery. AUTOPSY AND CASE REPORTS 2019; 9:e2019121. [PMID: 31641662 PMCID: PMC6771447 DOI: 10.4322/acr.2019.121] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2019] [Accepted: 08/20/2019] [Indexed: 11/25/2022] Open
Abstract
Plasminogen activator inhibitor-1 (PAI-1) is a biomarker of thrombosis. Adipose and vascular tissues are among the major sources of PAI-1 production. Previous studies indicated that fat deposits mediate increased cardiovascular risk among obese individuals. We investigated the immunohistochemical (IHC) expression of PAI-1 in adipose and vascular tissues from the omentum and the subcutaneous tissue. The pathology samples were selected from 37 random patients who underwent elective abdominal surgery between 2008-2009. PAI-1 expression was semi-quantitatively scored and compared between the groups. Significant differences were noted in the IHC expression of PAI-1 between the omental and the subcutaneous adipose tissues (1.1 ± 0.8 versus 0.8 ± 0.6, respectively (p=0.05)). Adipose tissue displayed higher IHC expression of PAI-1 compared to vascular wall tissue in both omentum and subcutaneous sections (1.1 ± 0.8 versus 0.5 ± 0.9 (p=0.004), and 0.8 ± 0.6 versus 0.4 ± 0.6 (p=0.003), respectively). In conclusion, our study compared PAI-1 expression in the omentum versus the subcutaneous tissue and adipose versus vascular tissues. IHC expression of PAI-1 level was significantly higher in the omental adipose tissue compared to the subcutaneous adipose tissue. Adipose tissue displayed significantly higher PAI-1 expression than vascular tissue. The study elucidates the biological differences of adipose and vascular tissue from subcutaneous versus omental sections.
Collapse
Affiliation(s)
- Mehmet Yildiz
- Cleveland Clinic Fairview Hospital, Department of Internal Medicine. Cleveland, OH, USA
| | - Emine Bozkurtlar
- Marmara University Medical School, Department of Pathology. Istanbul, Turkey
| | - Abdulmunir Azizy
- Marmara University, Medical School, Department of Medicine. Istanbul, Turkey
| | - Mehmet Agirbasli
- Medeniyet University Medical School, Department of Cardiology. Istanbul, Turkey
| |
Collapse
|
|
46
|
Ruiz-Ojeda FJ, Méndez-Gutiérrez A, Aguilera CM, Plaza-Díaz J. Extracellular Matrix Remodeling of Adipose Tissue in Obesity and Metabolic Diseases. Int J Mol Sci 2019; 20:4888. [PMID: 31581657 PMCID: PMC6801592 DOI: 10.3390/ijms20194888] [Citation(s) in RCA: 169] [Impact Index Per Article: 28.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2019] [Revised: 09/25/2019] [Accepted: 09/29/2019] [Indexed: 12/15/2022] Open
Abstract
The extracellular matrix (ECM) is a network of different proteins and proteoglycans that controls differentiation, migration, repair, survival, and development, and it seems that its remodeling is required for healthy adipose tissue expansion. Obesity drives an excessive lipid accumulation in adipocytes, which provokes immune cells infiltration, fibrosis (an excess of deposition of ECM components such as collagens, elastin, and fibronectin) and inflammation, considered a consequence of local hypoxia, and ultimately insulin resistance. To understand the mechanism of this process is a challenge to treat the metabolic diseases. This review is focused at identifying the putative role of ECM in adipose tissue, describing its structure and components, its main tissue receptors, and how it is affected in obesity, and subsequently the importance of an appropriate ECM remodeling in adipose tissue expansion to prevent metabolic diseases.
Collapse
Affiliation(s)
- Francisco Javier Ruiz-Ojeda
- Department of Biochemistry and Molecular Biology II, School of Pharmacy, University of Granada, 18071 Granada, Spain.
- Instituto de Investigación Biosanitaria IBS.GRANADA, Complejo Hospitalario Universitario de Granada, 18014 Granada, Spain.
- RG Adipocytes and metabolism, Institute for Diabetes and Obesity, Helmholtz Diabetes Center at Helmholtz Center Munich, 85764 Neuherberg, Munich, Germany.
| | - Andrea Méndez-Gutiérrez
- Department of Biochemistry and Molecular Biology II, School of Pharmacy, University of Granada, 18071 Granada, Spain.
- Instituto de Investigación Biosanitaria IBS.GRANADA, Complejo Hospitalario Universitario de Granada, 18014 Granada, Spain.
- Institute of Nutrition and Food Technology "José Mataix", Center of Biomedical Research, University of Granada, Avda. del Conocimiento s/n. 18016 Armilla, Granada, Spain.
- CIBEROBN (CIBER Physiopathology of Obesity and Nutrition), Instituto de Salud Carlos III, 28029 Madrid, Spain.
| | - Concepción María Aguilera
- Department of Biochemistry and Molecular Biology II, School of Pharmacy, University of Granada, 18071 Granada, Spain.
- Instituto de Investigación Biosanitaria IBS.GRANADA, Complejo Hospitalario Universitario de Granada, 18014 Granada, Spain.
- Institute of Nutrition and Food Technology "José Mataix", Center of Biomedical Research, University of Granada, Avda. del Conocimiento s/n. 18016 Armilla, Granada, Spain.
- CIBEROBN (CIBER Physiopathology of Obesity and Nutrition), Instituto de Salud Carlos III, 28029 Madrid, Spain.
| | - Julio Plaza-Díaz
- Department of Biochemistry and Molecular Biology II, School of Pharmacy, University of Granada, 18071 Granada, Spain.
- Instituto de Investigación Biosanitaria IBS.GRANADA, Complejo Hospitalario Universitario de Granada, 18014 Granada, Spain.
- Institute of Nutrition and Food Technology "José Mataix", Center of Biomedical Research, University of Granada, Avda. del Conocimiento s/n. 18016 Armilla, Granada, Spain.
| |
Collapse
|
|
47
|
Wade KNS, Brady MF, Thai T, Wang Y, Zheng B, Salani R, Tewari KS, Gray HJ, Bakkum-Gamez JN, Burger RA, Moore KN, Bookman MA. Measurements of adiposity as prognostic biomarkers for survival with anti-angiogenic treatment in epithelial ovarian cancer: An NRG Oncology/Gynecologic Oncology Group ancillary data analysis of GOG 218. Gynecol Oncol 2019; 155:69-74. [PMID: 31409486 PMCID: PMC7048388 DOI: 10.1016/j.ygyno.2019.07.020] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2019] [Revised: 07/16/2019] [Accepted: 07/19/2019] [Indexed: 11/22/2022]
Abstract
OBJECTIVE Adiposity has been hypothesized to interfere with the activity of bevacizumab (BEV), an anti-angiogenic agent. Measurements of adiposity, BMI, surface fat area (SFA), and visceral fat area (VFA) were investigated as prognostic of oncologic outcomes among patients treated with chemotherapy, with or without BEV, on GOG 218, a prospective phase III trial. METHOD Pretreatment computed tomography (CT) for 1538 GOG 218 participants were analyzed. Proportional hazards models assessed association between adiposity and overall survival (OS) adjusted for other prognostic factors. The predictive value of adiposity as a function of BEV treatment was assessed in 1019 patients randomized to either chemotherapy (CT) + placebo (P) → P or CT + BEV → BEV. RESULTS After adjusting for prognostic factors, SFA was not associated with the overall hazard of death (p = 0.981). There was a non-significant 0.1% (p = 0.062) increase in hazard of death associated with a unit increase in VFA. When comparing the treatment HRs for patients who did and did not receive BEV, there was no association with SFA (p = 0.890) or VFA (p = 0.106). A non-significant 0.8% increase in the hazard of death with unit increase in BMI (p = 0.086) was observed. BMI values were not predictive of a longer survival for patients with BEV vs placebo (p = 0.606). CONCLUSION Measures of adiposity strongly correlated to one another but were not predictive of efficacy for BEV. VFA is a weak prognostic factor.
Collapse
Affiliation(s)
| | - M F Brady
- NRG Oncology Statistical and Data Center, Roswell Park Cancer Institute, University of Buffalo, Buffalo, NY, USA.
| | - T Thai
- The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
| | - Y Wang
- The University of Oklahoma, Norman, OK, USA.
| | - B Zheng
- The University of Oklahoma, Norman, OK, USA.
| | - R Salani
- The Ohio State University, James Cancer Hospital, Columbus, OH, USA.
| | - K S Tewari
- UC Irvine Medical Center, Orange, CA, USA.
| | - H J Gray
- University of Washington Medical Center, Seattle, WA, USA.
| | | | - R A Burger
- University of Pennsylvania, Philadelphia, PA, USA.
| | - K N Moore
- The University of Oklahoma, Oklahoma City, OK, USA.
| | - M A Bookman
- US Oncology Research and Arizona Oncology, Tucson, AZ, USA.
| |
Collapse
|
|
48
|
Shen HH, Yang CY, Kung CW, Chen SY, Wu HM, Cheng PY, Lam KK, Lee YM. Raloxifene inhibits adipose tissue inflammation and adipogenesis through Wnt regulation in ovariectomized rats and 3 T3-L1 cells. J Biomed Sci 2019; 26:62. [PMID: 31470850 PMCID: PMC6717377 DOI: 10.1186/s12929-019-0556-3] [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] [Subscribe] [Scholar Register] [Received: 03/05/2019] [Accepted: 08/22/2019] [Indexed: 01/17/2023] Open
Abstract
BACKGROUND Loss of ovarian function, as in menopause or after ovariectomy (OVX), is closely associated with obesity and white adipose tissue (WAT) inflammation. Estrogen replacement protects against postmenopausal obesity but increases the risks of carcinogenesis. In the present study, we investigated the effects of long-term treatment of raloxifene (RAL), a selective estrogen receptor modulator, on the features of estrogen deficiency-induced obesity and explored the involvement of canonical and non-canonical Wnt regulation in vivo and in vitro. METHODS Adult female rats received bilateral OVX and divided into 5 groups: (1) Sham, (2) OVX, (3) OVX + E2: OVX rats were administered with E2 (50 μg/kg, s.c., 3 times/week), (4) OVX + RAL: OVX rats were treated with RAL (gavage, 1 mg/kg/day) suspended in 0.8% carboxymethylcellulose (CMC), (5) OVX + CMC: 0.8% CMC as vehicle control. All treatments were given for 8 weeks beginning at 1 week after OVX. In 3 T3-L1 cells, the effects of RAL on adipogenesis and lipopolysaccharide (LPS)-induced inflammation were evaluated. RESULTS Treatment with RAL significantly decreased body weight, visceral fat pad mass, adipocyte size and plasma levels of glucose but increased plasma adiponectin. RAL reduced the elevation of HIF-1α, VEGF-A and proinflammatory cytokines (MCP-1 and TNF-α) expression by inhibition of NF-κB p65 and JNK cascades in retroperitoneal WAT. This anti-inflammatory capacity of RAL may result from upregulation of secreted frizzle-related protein 5 (SFRP5), an adipokine that repressed Wnt5a signaling. Furthermore, RAL inhibited adipogenic factors such as PPAR-γ, C/EBP-α, and FABP4, and preserved canonical Wnt10b/β-catenin protein expression. In 3 T3-L1 adipocytes, RAL (20 μM) diminished lipid accumulation and inhibited adipogenic factors accompanied with the induction of β-catenin, which were effectively reversed by the β-catenin inhibitor IWR-1-endo. In addition, RAL reduced LPS-induced NF-κB p65 and p-IκB expression as well as TNF-α secretion. Suppression of SFRP5 by small interfering RNA significantly abrogated the anti-inflammatory effects of RAL. CONCLUSIONS Distinct activation of canonical β-catenin on inhibition of adipogenesis and non-canonical SFRP5 on suppression of WAT inflammation may contribute to the beneficial effects of RAL. Therefore, this study provides a rationale for the therapeutic potential of RAL for postmenopausal obesity.
Collapse
Affiliation(s)
- Hsin-Hsueh Shen
- 0000 0004 0634 0356grid.260565.2Department and Institute of Pharmacology, National Defense Medical Center, Taipei, Taiwan
- 0000 0004 0634 0356grid.260565.2Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan
- 0000 0004 0634 0356grid.260565.2Department of Pharmacy Practice, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Chien-Yi Yang
- 0000 0004 0638 9360grid.278244.fDivision of General Surgery, Department of Surgery, Tri-Service General Hospital Sungshan Branch, Taipei, Taiwan
| | - Ching-Wen Kung
- 0000 0004 0622 7222grid.411824.aDepartment of Nursing, Tzu Chi University of Science and Technology, Hualien, Taiwan
| | - Shu-Ying Chen
- 0000 0004 1770 3722grid.411432.1Department of Nursing, Hung Kuang University, Taichung, Taiwan
| | - Hong-Min Wu
- 0000 0004 0634 0356grid.260565.2Department and Institute of Pharmacology, National Defense Medical Center, Taipei, Taiwan
| | - Pao-Yun Cheng
- 0000 0004 0634 0356grid.260565.2Department of Physiology & Biophysics, National Defense Medical Center, Taipei, Taiwan
| | - Kwok-Keung Lam
- 0000 0000 9337 0481grid.412896.0Department of Pharmacology, Taipei Medical University, Taipei, Taiwan
- Department of Anesthesiology, Catholic Mercy Hospital, Hsinchu, Taiwan
| | - Yen-Mei Lee
- 0000 0004 0634 0356grid.260565.2Department and Institute of Pharmacology, National Defense Medical Center, Taipei, Taiwan
| |
Collapse
|
|
49
|
Artaç M, Korkmaz L, Coşkun HŞ, Dane F, Karabulut B, Karaağaç M, Çabuk D, Karabulut S, Aykan NF, Doruk H, Avcı N, Turhal NS. Bevacuzimab May Be Less Effective in Obese Metastatic Colorectal Cancer Patients. J Gastrointest Cancer 2019; 50:214-220. [PMID: 29302856 DOI: 10.1007/s12029-017-0047-2] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
PURPOSE The purpose of this study was to investigate whether obesity affects survival in metastatic colorectal cancer (mCRC) patients treated with bevacizumab combined with chemotherapy. METHODS A total of 563 patients with mCRC who had received first-line chemotherapy in combination with bevacizumab were studied. Patients were grouped as obese (BMI levels > 30) or non-obese (BMI levels < 30). Progression-free survival (PFS) and overall survival (OS) were analyzed. Primary tumor location was also investigated in terms of PFS and OS. RESULTS The median age of the patients was 59 years. The non-obese group had longer PFS than the obese group (P = 0.030). The 2-year survival rate of the non-obese group was also significantly higher (P = 0.036). The median PFS of non-obese patients was significantly longer in Kras wild-type patients (10.1 vs. 8.1 months, P = 0.010). Among patients with left-sided primary tumor location, median PFS and OS were significantly higher in the non-obese group (PFS non-obese, 11.5 months; obese, 8.8 months; P = 0.002) (OS non-obese, 29.4 months; obese, 21.4 months; P = 0.026). CONCLUSIONS Efficacy of bevacizumab may be lower in obese patients. Among patients with Kras wild-type left-sided tumors treated with bevacizumab-based regimens, the prognosis could be worse for obese patients than that for non-obese patients. There is a need for prospectively designed studies of obese patients to prove the efficacy and dosages of bevacizumab in treatment of mCRC.
Collapse
Affiliation(s)
- Mehmet Artaç
- Department of Medical Oncology, Meram Faculty of Medicine, Necmettin Erbakan University, 42080, Konya, Turkey.
| | - Levent Korkmaz
- Department of Medical Oncology, Meram Faculty of Medicine, Necmettin Erbakan University, 42080, Konya, Turkey
| | - Hasan Şenol Coşkun
- Department of Medical Oncology, Faculty of Medicine, Akdeniz University, Antalya, Turkey
| | - Faysal Dane
- Department of Medical Oncology, Faculty of Medicine, Marmara University, Istanbul, Turkey
| | - Bülent Karabulut
- Department of Medical Oncology, Faculty of Medicine, Ege University, Izmir, Turkey
| | - Mustafa Karaağaç
- Department of Medical Oncology, Meram Faculty of Medicine, Necmettin Erbakan University, 42080, Konya, Turkey
| | - Devrim Çabuk
- Department of Medical Oncology, Faculty of Medicine, Kocaeli University, Kocaeli, Turkey
| | - Senem Karabulut
- Department of Medical Oncology, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey
| | - Nuri Faruk Aykan
- Department of Medical Oncology, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey
| | - Hatice Doruk
- Department of Medical Oncology, Acıbadem Bursa Hospital, Bursa, Turkey
| | - Nilüfer Avcı
- Department of Medical Oncology, Ali Osman Sönmez Oncology Hospital, Bursa, Turkey
| | | |
Collapse
|
|
50
|
Mundi S, Massaro M, Scoditti E, Carluccio MA, van Hinsbergh VWM, Iruela-Arispe ML, De Caterina R. Endothelial permeability, LDL deposition, and cardiovascular risk factors-a review. Cardiovasc Res 2019; 114:35-52. [PMID: 29228169 DOI: 10.1093/cvr/cvx226] [Citation(s) in RCA: 216] [Impact Index Per Article: 36.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2017] [Accepted: 12/05/2017] [Indexed: 12/21/2022] Open
Abstract
Early atherosclerosis features functional and structural changes in the endothelial barrier function that affect the traffic of molecules and solutes between the vessel lumen and the vascular wall. Such changes are mechanistically related to the development of atherosclerosis. Proatherogenic stimuli and cardiovascular risk factors, such as dyslipidaemias, diabetes, obesity, and smoking, all increase endothelial permeability sharing a common signalling denominator: an imbalance in the production/disposal of reactive oxygen species (ROS), broadly termed oxidative stress. Mostly as a consequence of the activation of enzymatic systems leading to ROS overproduction, proatherogenic factors lead to a pro-inflammatory status that translates in changes in gene expression and functional rearrangements, including changes in the transendothelial transport of molecules, leading to the deposition of low-density lipoproteins (LDL) and the subsequent infiltration of circulating leucocytes in the intima. In this review, we focus on such early changes in atherogenesis and on the concept that proatherogenic stimuli and risk factors for cardiovascular disease, by altering the endothelial barrier properties, co-ordinately trigger the accumulation of LDL in the intima and ultimately plaque formation.
Collapse
Affiliation(s)
- Santa Mundi
- Department of Biological and Environmental Science and Technology (DISTEBA), University of Salento, via Monteroni, 73100, Lecce, Italy
| | - Marika Massaro
- National Research Council (CNR), Department of Biomedical sciences, Institute of Clinical Physiology, Via Monteroni, 73100, Lecce, Italy
| | - Egeria Scoditti
- National Research Council (CNR), Department of Biomedical sciences, Institute of Clinical Physiology, Via Monteroni, 73100, Lecce, Italy
| | - Maria Annunziata Carluccio
- National Research Council (CNR), Department of Biomedical sciences, Institute of Clinical Physiology, Via Monteroni, 73100, Lecce, Italy
| | - Victor W M van Hinsbergh
- Department of Physiology, Institute for Cardiovascular Research, VU University Medical Center, van der Boechorststraat, NL-1081 BT, Amsterdam, The Netherlands
| | - Marial Luisa Iruela-Arispe
- Department of Molecular, Cell and Developmental Biology and Molecular Biology Institute, University of California, 610 Charles E Young Dr S, 90095, Los Angeles, USA; and
| | - Raffaele De Caterina
- Department of Neuroscience, Imaging and Clinical Science and Institute of Advanced Biomedical Technologies, University G. D'Annunzio, via dei Vestini, 66100 Chieti, Italy
| |
Collapse
|