|
1
|
Guo Z, Li H, Jiang S, Rahmati M, Su J, Yang S, Wu Y, Li Y, Deng Z. The role of AGEs in muscle ageing and sarcopenia. Bone Joint Res 2025; 14:185-198. [PMID: 40036085 PMCID: PMC11878473 DOI: 10.1302/2046-3758.143.bjr-2024-0252.r1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/06/2025] Open
Abstract
Sarcopenia is an ageing-related disease featured by the loss of skeletal muscle quality and function. Advanced glycation end-products (AGEs) are a complex set of modified proteins or lipids by non-enzymatic glycosylation and oxidation. The formation of AGEs is irreversible, and they accumulate in tissues with increasing age. Currently, AGEs, as a biomarker of ageing, are viewed as a risk factor for sarcopenia. AGE accumulation could cause harmful effects in the human body such as elevated inflammation levels, enhanced oxidative stress, and targeted glycosylation of proteins inside and outside the cells. Several studies have illustrated the pathogenic role of AGEs in sarcopenia, which includes promoting skeletal muscle atrophy, impairing muscle regeneration, disrupting the normal structure of skeletal muscle extracellular matrix, and contributing to neuromuscular junction lesion and vascular disorders. This article reviews studies focused on the pathogenic role of AGEs in sarcopenia and the potential mechanisms of the detrimental effects, aiming to provide new insights into the pathogenesis of sarcopenia and develop novel methods for the prevention and therapy of sarcopenia.
Collapse
Affiliation(s)
- Zhaojing Guo
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, China
- Xiangya School of Medicine, Central South University, Changsha, China
| | - Hengzhen Li
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Shide Jiang
- The Central Hospital of Yongzhou, Yongzhou, China
| | - Masoud Rahmati
- Department of Physical Education and Sport Sciences, Faculty of Literature and Human Sciences, Lorestan University, Khorramabad, Iran
- Department of Physical Education and Sport Sciences, Faculty of Literature and Humanities, Vali-E-Asr University of Rafsanjan, Rafsanjan, Iran
| | - Jingyue Su
- Department of Orthopedics, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
- Geriatrics Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Shengwu Yang
- Department of Orthopedics, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
- Geriatrics Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Yuxiang Wu
- Department of Health and Physical Education, Jianghan University, Wuhan, China
| | - Yusheng Li
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Zhenhan Deng
- Department of Orthopedics, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
- Geriatrics Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| |
Collapse
|
|
2
|
Garza-Campos A, Prieto-Correa JR, Domínguez-Rosales JA, Hernández-Nazará ZH. Implications of receptor for advanced glycation end products for progression from obesity to diabetes and from diabetes to cancer. World J Diabetes 2023; 14:977-994. [PMID: 37547586 PMCID: PMC10401444 DOI: 10.4239/wjd.v14.i7.977] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2023] [Revised: 01/31/2023] [Accepted: 04/17/2023] [Indexed: 07/12/2023] Open
Abstract
Obesity and type 2 diabetes mellitus (T2DM) are chronic pathologies with a high incidence worldwide. They share some pathological mechanisms, including hyperinsulinemia, the production and release of hormones, and hyperglycemia. The above, over time, affects other systems of the human body by causing tissue hypoxia, low-grade inflammation, and oxidative stress, which lay the pathophysiological groundwork for cancer. The leading causes of death globally are T2DM and cancer. Other main alterations of this pathological triad include the accumulation of advanced glycation end products and the release of endogenous alarmins due to cell death (i.e., damage-associated molecular patterns) such as the intracellular proteins high-mobility group box protein 1 and protein S100 that bind to the receptor for advanced glycation products (RAGE) - a multiligand receptor involved in inflammatory and metabolic and neoplastic processes. This review analyzes the latest advanced reports on the role of RAGE in the development of obesity, T2DM, and cancer, with an aim to understand the intracellular signaling mechanisms linked with cancer initiation. This review also explores inflammation, oxidative stress, hypoxia, cellular senescence, RAGE ligands, tumor microenvironment changes, and the “cancer hallmarks” of the leading tumors associated with T2DM. The assimilation of this information could aid in the development of diagnostic and therapeutic approaches to lower the morbidity and mortality associated with these diseases.
Collapse
Affiliation(s)
- Andrea Garza-Campos
- Programa de Doctorado en Ciencias en Biología Molecular en Medicina, Universidad de Guadalajara, Guadalajara 44340, Jalisco, Mexico
- Departamento de Biología Molecular y Genómica, Instituto de Investigación en Enfermedades Crónico-Degenerativas, Universidad de Guadalajara, Guadalajara 44340, Jalisco, Mexico
| | - José Roberto Prieto-Correa
- Programa de Doctorado en Ciencias en Biología Molecular en Medicina, Universidad de Guadalajara, Guadalajara 44340, Jalisco, Mexico
- Departamento de Biología Molecular y Genómica, Instituto de Investigación en Enfermedades Crónico-Degenerativas, Universidad de Guadalajara, Guadalajara 44340, Jalisco, Mexico
| | - José Alfredo Domínguez-Rosales
- Departamento de Biología Molecular y Genómica, Instituto de Investigación en Enfermedades Crónico-Degenerativas, Universidad de Guadalajara, Guadalajara 44340, Jalisco, Mexico
| | - Zamira Helena Hernández-Nazará
- Departamento de Biología Molecular y Genómica, Instituto de Investigación en Enfermedades Crónico-Degenerativas, Universidad de Guadalajara, Guadalajara 44340, Jalisco, Mexico
| |
Collapse
|
|
3
|
Tsubokawa M, Nishimura M, Murashita K, Iwane T, Tamada Y. Correlation between Glycation-Related Biomarkers and Quality of Life in the General Japanese Population: The Iwaki Cross-Sectional Research Study. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:ijerph19159391. [PMID: 35954745 PMCID: PMC9368172 DOI: 10.3390/ijerph19159391] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 06/01/2022] [Revised: 07/21/2022] [Accepted: 07/28/2022] [Indexed: 11/27/2022]
Abstract
The correlation between diabetes-related biomarkers and quality of life (QOL) remains unclear. In this cross-sectional study, we investigated the correlation between diabetes-related biomarkers and QOL in a general Japanese population who underwent health checkups as a part of the Iwaki Health Promotion Project. Male and female participants aged ≥ 20 years from Iwaki District, Hirosaki City, Aomori Prefecture who participated in the 2019 medical evaluation were recruited. QOL was evaluated using the Short Form Health Survey 36 (SF-36). Fasting blood glucose, homeostatic model assessment-estimated insulin resistance (HOMA-IR), hemoglobin A1c (HbA1c), glycoalbumin, and plasma pentosidine were also evaluated as diabetes-related markers. Of the 1065 recruited participants, 1053 completed the clinical and QOL evaluations. Multivariate regression analysis revealed that upregulated diabetes-related markers levels were correlated with decreased SF-36 scores. Blood glucose, HOMA-IR, HbA1c, glycoalbumin, and plasma pentosidine levels were correlated with general health. Moreover, plasma pentosidine levels were correlated with role physical, social functioning, and role emotional in addition to general health. These results indicated that the levels of diabetes-related biomarkers, particularly the levels of plasma pentosidine, a glycation marker, were associated with QOL in our cohort.
Collapse
Affiliation(s)
- Masaya Tsubokawa
- Innovation Center for Health Promotion, Graduate School of Medicine, Hirosaki University, Hirosaki 036-8562, Japan;
- Health Science Research Center, FANCL Research Institute, Yokohama 244-0806, Japan;
- Correspondence: ; Tel.: +81-045-820-3659
| | - Miyuki Nishimura
- Health Science Research Center, FANCL Research Institute, Yokohama 244-0806, Japan;
| | - Koichi Murashita
- Center of Innovation Research Initiatives Organization, Hirosaki University, Hirosaki 036-8562, Japan; (K.M.); (T.I.)
| | - Takuro Iwane
- Center of Innovation Research Initiatives Organization, Hirosaki University, Hirosaki 036-8562, Japan; (K.M.); (T.I.)
| | - Yoshinori Tamada
- Innovation Center for Health Promotion, Graduate School of Medicine, Hirosaki University, Hirosaki 036-8562, Japan;
| |
Collapse
|
|
4
|
Mehmood H, Haroon M, Akhtar T, Woodward S, Andleeb H. Synthesis and molecular docking studies of 5-acetyl-2-(arylidenehydrazin-1-yl)-4-methyl-1,3-thiazoles as α-amylase inhibitors. J Mol Struct 2022. [DOI: 10.1016/j.molstruc.2021.131807] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
|
|
5
|
Moriwaki K, Matsumoto H, Tanimura C, Osaki M, Nagashima H, Hagino H. Urinary pentosidine level is associated with grip strength and gait speed in community-dwelling adults: a cross-sectional study. BMC Musculoskelet Disord 2021; 22:392. [PMID: 33902533 PMCID: PMC8077690 DOI: 10.1186/s12891-021-04279-5] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2020] [Accepted: 04/20/2021] [Indexed: 01/22/2023] Open
Abstract
Background Muscle and bone interactions might be associated with osteoporosis and sarcopenia. Urinary pentosidine and serum 25-hydroxyvitamin D (25(OH)D) might affect muscle and bone interactions. It is unclear whether these biomarkers are affected by age and sex or play a role in muscle and physical functions. We aimed to investigate the association between urinary pentosidine and serum 25(OH)D levels with muscle mass, muscle strength, and physical performance in community-dwelling adults. Methods Two-hundred and fifty-four middle-aged and elderly adults were enrolled. There was no significant difference in age between 97 men (75.0 ± 8.9 years) and 157 women (73.6 ± 8.1 years). The skeletal muscle mass index (SMI), grip strength, and gait speed were assessed. The urinary pentosidine level was measured. We evaluated the association of urinary pentosidine and serum 25(OH)D levels with age and sex (student’s t-test) and correlations between biomarker and each variable (Pearson’s correlation coefficients). Multiple regression analysis was performed with grip strength and gait speed as dependent variables and with age, height, weight, body mass index (BMI), speed of sound (SOS), SMI, glycated hemoglobin (HbA1c), estimated glomerular filtration rate (eGFR), 25(OH)D, and pentosidine as independent variables using the stepwise method. Results The urinary pentosidine level was negatively correlated with grip strength, gait speed, eGFR, and insulin-like growth factor-1 (IGF-1) in men and with SOS, grip strength, and gait speed in women. The serum 25(OH)D level was positively correlated with IGF-1 in women and grip strength in men. Grip strength was associated with age, height, and pentosidine in men and height and pentosidine in women. Gait speed was associated with age, BMI, and pentosidine in men and age, height, and pentosidine in women. Conclusion Urinary pentosidine levels are significantly associated with grip strength and gait speed and may serve as a biomarker of muscle and bone interactions.
Collapse
Affiliation(s)
- Kenta Moriwaki
- Department of Orthopedic Surgery, Faculty of Medicine, Tottori University, Nishicho 36-1, Yonago, Tottori, 683-8504, Japan. .,Department of Orthopedic Surgery, Misasa Onsen Hospital, Yamada 690Misasa, Tottori, 682-0122, Japan.
| | - Hiromi Matsumoto
- Department of Rehabilitation, Faculty of Health Science and Technology, Kawasaki University of Medical Welfare, Matsushima 288, Kurashiki, Okayama, 701-0193, Japan
| | - Chika Tanimura
- School of Health Science, Faculty of Medicine, Tottori University, Nishicho 86, Yonago, Tottori, 683-8504, Japan
| | - Mari Osaki
- Rehabilitation Division, Tottori University Hospital, Nishicho 36-1, Yonago, Tottori, 683-8504, Japan
| | - Hideki Nagashima
- Department of Orthopedic Surgery, Faculty of Medicine, Tottori University, Nishicho 36-1, Yonago, Tottori, 683-8504, Japan
| | - Hiroshi Hagino
- School of Health Science, Faculty of Medicine, Tottori University, Nishicho 86, Yonago, Tottori, 683-8504, Japan.,Rehabilitation Division, Tottori University Hospital, Nishicho 36-1, Yonago, Tottori, 683-8504, Japan
| |
Collapse
|
|
6
|
Yabuuchi J, Ueda S, Yamagishi SI, Nohara N, Nagasawa H, Wakabayashi K, Matsui T, Yuichiro H, Kadoguchi T, Otsuka T, Gohda T, Suzuki Y. Association of advanced glycation end products with sarcopenia and frailty in chronic kidney disease. Sci Rep 2020; 10:17647. [PMID: 33077879 PMCID: PMC7573579 DOI: 10.1038/s41598-020-74673-x] [Citation(s) in RCA: 47] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2020] [Accepted: 10/05/2020] [Indexed: 12/27/2022] Open
Abstract
Prevalence of sarcopenia is high in patients with chronic kidney disease (CKD), especially in those with dialysis. Various pathological conditions related to CKD, such as chronic inflammation, insulin resistance, and endothelial dysfunction, are thought to be associated with the development and progression of sarcopenia. Advanced glycation end products (AGE), one of the representative uremic toxins, have been shown to contribute to various CKD-associated complications. This study investigated the role of AGE in frailty and sarcopenia in patients and animals with CKD, respectively. In patients undergoing dialysis, serum AGE levels were significantly increased according to the frailty status and inversely associated with physical performance and activity. AGE accumulated in the gastrocnemius muscle of 5/6 nephrectomy mice in association with morphological abnormalities, capillary rarefaction, and mitochondrial dysfunction, all of which were completely inhibited by DNA-aptamer raised against AGE. Our present findings may suggest the pathological role of AGE in sarcopenia and frailty in CKD.
Collapse
Affiliation(s)
- Junko Yabuuchi
- Department of Nephrology, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan
| | - Seiji Ueda
- Department of Nephrology, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
| | - Sho-Ichi Yamagishi
- Division of Diabetes, Metabolism and Endocrinology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan
| | - Nao Nohara
- Department of Nephrology, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan
| | - Hajime Nagasawa
- Department of Nephrology, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan
| | - Keiichi Wakabayashi
- Department of Nephrology, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan
| | - Takanori Matsui
- Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume, Japan
| | | | - Tomoyasu Kadoguchi
- Department of Cardiovascular Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Tomoyuki Otsuka
- Department of Nephrology, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan
| | - Tomohito Gohda
- Department of Nephrology, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan
| | - Yusuke Suzuki
- Department of Nephrology, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan
| |
Collapse
|
|
7
|
Strieder-Barboza C, Baker NA, Flesher CG, Karmakar M, Neeley CK, Polsinelli D, Dimick JB, Finks JF, Ghaferi AA, Varban OA, Lumeng CN, O'Rourke RW. Advanced glycation end-products regulate extracellular matrix-adipocyte metabolic crosstalk in diabetes. Sci Rep 2019; 9:19748. [PMID: 31875018 PMCID: PMC6930305 DOI: 10.1038/s41598-019-56242-z] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2019] [Accepted: 12/07/2019] [Indexed: 12/28/2022] Open
Abstract
The adipose tissue extracellular matrix (ECM) regulates adipocyte cellular metabolism and is altered in obesity and type 2 diabetes, but mechanisms underlying ECM-adipocyte metabolic crosstalk are poorly defined. Advanced glycation end-product (AGE) formation is increased in diabetes. AGE alter tissue function via direct effects on ECM and by binding scavenger receptors on multiple cell types and signaling through Rho GTPases. Our goal was to determine the role and underlying mechanisms of AGE in regulating human ECM-adipocyte metabolic crosstalk. Visceral adipocytes from diabetic and non-diabetic humans with obesity were studied in 2D and 3D-ECM culture systems. AGE is increased in adipose tissue from diabetic compared to non-diabetic subjects. Glycated collagen 1 and AGE-modified ECM regulate adipocyte glucose uptake and expression of AGE scavenger receptors and Rho signaling mediators, including the DIAPH1 gene, which encodes the human Diaphanous 1 protein (hDia1). Notably, inhibition of hDia1, but not scavenger receptors RAGE or CD36, attenuated AGE-ECM inhibition of adipocyte glucose uptake. These data demonstrate that AGE-modification of ECM contributes to adipocyte insulin resistance in human diabetes, and implicate hDia1 as a potential mediator of AGE-ECM-adipocyte metabolic crosstalk.
Collapse
Affiliation(s)
- Clarissa Strieder-Barboza
- Department of Surgery, University of Michigan Medical School, Ann Arbor, MI, USA
- Department of Pediatrics and Communicable Diseases, University of Michigan Medical School, Ann Arbor, MI, USA
| | - Nicki A Baker
- Department of Surgery, University of Michigan Medical School, Ann Arbor, MI, USA
| | - Carmen G Flesher
- Department of Surgery, University of Michigan Medical School, Ann Arbor, MI, USA
| | - Monita Karmakar
- Department of Surgery, University of Michigan Medical School, Ann Arbor, MI, USA
| | - Christopher K Neeley
- Department of Surgery, University of Michigan Medical School, Ann Arbor, MI, USA
| | - Dominic Polsinelli
- Undergraduate Research Opportunity Program, University of Michigan, Ann Arbor, MI, USA
| | - Justin B Dimick
- Department of Surgery, University of Michigan Medical School, Ann Arbor, MI, USA
| | - Jonathan F Finks
- Department of Surgery, University of Michigan Medical School, Ann Arbor, MI, USA
| | - Amir A Ghaferi
- Department of Surgery, University of Michigan Medical School, Ann Arbor, MI, USA
| | - Oliver A Varban
- Department of Surgery, University of Michigan Medical School, Ann Arbor, MI, USA
| | - Carey N Lumeng
- Department of Pediatrics and Communicable Diseases, University of Michigan Medical School, Ann Arbor, MI, USA
- Graduate Program in Immunology, University of Michigan Medical School, Ann Arbor, MI, USA
- Graduate Program in Cellular and Molecular Biology, University of Michigan Medical School, Ann Arbor, MI, USA
| | - Robert W O'Rourke
- Department of Surgery, University of Michigan Medical School, Ann Arbor, MI, USA.
- Department of Surgery, Ann Arbor Veterans Affairs Healthcare System, Ann Arbor, MI, USA.
| |
Collapse
|
|
8
|
Mori H, Kuroda A, Ishizu M, Ohishi M, Takashi Y, Otsuka Y, Taniguchi S, Tamaki M, Kurahashi K, Yoshida S, Endo I, Aihara K, Funaki M, Akehi Y, Matsuhisa M. Association of accumulated advanced glycation end-products with a high prevalence of sarcopenia and dynapenia in patients with type 2 diabetes. J Diabetes Investig 2019; 10:1332-1340. [PMID: 30677242 PMCID: PMC6717916 DOI: 10.1111/jdi.13014] [Citation(s) in RCA: 66] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2018] [Revised: 01/17/2019] [Accepted: 01/17/2019] [Indexed: 12/12/2022] Open
Abstract
AIMS/INTRODUCTION Advanced glycation end-products (AGEs), which are a major cause of diabetic vascular complications, accumulate in various tissues under chronic hyperglycemic conditions, as well as with aging in patients with diabetes. The loss of muscle mass and strength, so-called sarcopenia and dynapenia, has recently been recognized as a diabetic complication. However, the influence of accumulated AGEs on muscle mass and strength remains unclear. The present study aimed to evaluate the association of sarcopenia and dynapenia with accumulated AGEs in patients with type 2 diabetes. MATERIALS AND METHODS We recruited 166 patients with type 2 diabetes aged ≥30 years (mean age 63.2 ± 12.3 years; body mass index 26.3 ± 4.9 kg/m2 ; glycated hemoglobin 7.1 ± 1.1%). Skin autofluorescence as a marker of AGEs, limb skeletal muscle mass index, grip strength, knee extension strength and gait speed were assessed. RESULTS Sarcopenia and dynapenia were observed in 7.2 and 13.9% of participants, respectively. Skin autofluorescence was significantly higher in patients with sarcopenia and dynapenia. Skin autofluorescence was the independent determinant for skeletal muscle mass index, grip strength, knee extension strength, sarcopenia and dynapenia. CONCLUSIONS Accumulated AGEs could contribute to reduced muscle mass and strength, leading to sarcopenia and dynapenia in patients with type 2 diabetes.
Collapse
Affiliation(s)
- Hiroyasu Mori
- Diabetes Therapeutics and Research CenterInstitute of Advanced Medical SciencesTokushima UniversityTokushimaJapan
| | - Akio Kuroda
- Diabetes Therapeutics and Research CenterInstitute of Advanced Medical SciencesTokushima UniversityTokushimaJapan
| | - Masashi Ishizu
- Diabetes Therapeutics and Research CenterInstitute of Advanced Medical SciencesTokushima UniversityTokushimaJapan
- Department of Hematology, Endocrinology and MetabolismTokushima University Graduate School of Biomedical SciencesTokushimaJapan
| | - Mami Ohishi
- Diabetes Therapeutics and Research CenterInstitute of Advanced Medical SciencesTokushima UniversityTokushimaJapan
| | - Yuichi Takashi
- Diabetes Therapeutics and Research CenterInstitute of Advanced Medical SciencesTokushima UniversityTokushimaJapan
| | - Yinhua Otsuka
- Diabetes Therapeutics and Research CenterInstitute of Advanced Medical SciencesTokushima UniversityTokushimaJapan
| | - Satoshi Taniguchi
- Diabetes Therapeutics and Research CenterInstitute of Advanced Medical SciencesTokushima UniversityTokushimaJapan
| | - Motoyuki Tamaki
- Diabetes Therapeutics and Research CenterInstitute of Advanced Medical SciencesTokushima UniversityTokushimaJapan
| | - Kiyoe Kurahashi
- Department of Hematology, Endocrinology and MetabolismTokushima University Graduate School of Biomedical SciencesTokushimaJapan
| | - Sumiko Yoshida
- Department of Hematology, Endocrinology and MetabolismTokushima University Graduate School of Biomedical SciencesTokushimaJapan
| | - Itsuro Endo
- Department of Hematology, Endocrinology & MetabolismInstitute of Biomedical SciencesTokushima University Graduate School of Biomedical SciencesTokushimaJapan
| | - Ken‐ichi Aihara
- Department of Community Medicine for Diabetes and Metabolic DisordersTokushima University Graduate School of Biomedical SciencesTokushimaJapan
| | - Makoto Funaki
- Clinical Research Center for DiabetesTokushima University HospitalTokushimaJapan
| | - Yuko Akehi
- Diabetes Therapeutics and Research CenterInstitute of Advanced Medical SciencesTokushima UniversityTokushimaJapan
| | - Munehide Matsuhisa
- Diabetes Therapeutics and Research CenterInstitute of Advanced Medical SciencesTokushima UniversityTokushimaJapan
| |
Collapse
|
|
9
|
Silva DM, Queiroz NP, Freitas ATVS, Passarelli M, Corgosinho¹ FC, Peixoto MDRG. Serum advanced glycation end products are not associated with muscle strength in hemodialysis patients. Eur J Clin Nutr 2019; 73:617-623. [DOI: 10.1038/s41430-018-0379-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2018] [Revised: 11/28/2018] [Accepted: 12/03/2018] [Indexed: 01/03/2023]
|
|
10
|
Riuzzi F, Sorci G, Sagheddu R, Chiappalupi S, Salvadori L, Donato R. RAGE in the pathophysiology of skeletal muscle. J Cachexia Sarcopenia Muscle 2018; 9:1213-1234. [PMID: 30334619 PMCID: PMC6351676 DOI: 10.1002/jcsm.12350] [Citation(s) in RCA: 81] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2018] [Revised: 07/20/2018] [Accepted: 08/24/2018] [Indexed: 12/14/2022] Open
Abstract
Emerging evidence suggests that the signalling of the Receptor for Advanced Glycation End products (RAGE) is critical for skeletal muscle physiology controlling both the activity of muscle precursors during skeletal muscle development and the correct time of muscle regeneration after acute injury. On the other hand, the aberrant re-expression/activity of RAGE in adult skeletal muscle is a hallmark of muscle wasting that occurs in response to ageing, genetic disorders, inflammatory conditions, cancer, and metabolic alterations. In this review, we discuss the mechanisms of action and the ligands of RAGE involved in myoblast differentiation, muscle regeneration, and muscle pathological conditions. We highlight potential therapeutic strategies for targeting RAGE to improve skeletal muscle function.
Collapse
Affiliation(s)
- Francesca Riuzzi
- Department of Experimental Medicine, University of Perugia, Perugia, Italy.,Interuniversity Institute of Myology
| | - Guglielmo Sorci
- Department of Experimental Medicine, University of Perugia, Perugia, Italy.,Interuniversity Institute of Myology
| | - Roberta Sagheddu
- Department of Experimental Medicine, University of Perugia, Perugia, Italy.,Interuniversity Institute of Myology
| | - Sara Chiappalupi
- Department of Experimental Medicine, University of Perugia, Perugia, Italy.,Interuniversity Institute of Myology
| | - Laura Salvadori
- Department of Experimental Medicine, University of Perugia, Perugia, Italy.,Interuniversity Institute of Myology
| | - Rosario Donato
- Department of Experimental Medicine, University of Perugia, Perugia, Italy.,Interuniversity Institute of Myology.,Centro Universitario di Ricerca sulla Genomica Funzionale, University of Perugia, Perugia, Italy
| |
Collapse
|
|
11
|
Nowotny K, Schröter D, Schreiner M, Grune T. Dietary advanced glycation end products and their relevance for human health. Ageing Res Rev 2018; 47:55-66. [PMID: 29969676 DOI: 10.1016/j.arr.2018.06.005] [Citation(s) in RCA: 170] [Impact Index Per Article: 24.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2018] [Revised: 06/26/2018] [Accepted: 06/27/2018] [Indexed: 12/23/2022]
Abstract
Due to their bioactivity and harmful potential, advanced glycation end products (AGEs) are discussed to affect human health. AGEs are compounds formed endogenously in the human body andexogenously, especially, in foods while thermal processing. In contrast to endogenous AGEs, dietary AGEs are formed in much higher extent. However, their risk potential is also depending on absorption, distribution, metabolism and elimination. For over 10 years an intense debate on the risk of dietary AGEs on human health is going on. On the one hand, studies provided evidence that dietary AGEs contribute to clinical outcomes. On the other hand, human studies failed to observe any association. Because it was not possible to draw a final conclusion, the call for new interdisciplinary approaches arose. In this review, we will give an overview on the current state of scientific knowledge in this field. In particular, we focus on (I) the occurrence of AGEs in foods and the daily uptake of AGEs, (II) contribution to endogenous levels and (III) the effect on health-/disease-related biomarkers in humans.
Collapse
Affiliation(s)
- Kerstin Nowotny
- Department of Molecular Toxicology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), 14558 Nuthetal, Germany
| | - David Schröter
- Department of Molecular Toxicology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), 14558 Nuthetal, Germany; Leibniz Institute of Vegetable and Ornamental Crops Grossbeeren e.V. (IGZ), 14979 Grossbeeren, Germany; Institute of Food Chemistry, Hamburg School of Food Science, University of Hamburg, 20146 Hamburg, Germany
| | - Monika Schreiner
- Leibniz Institute of Vegetable and Ornamental Crops Grossbeeren e.V. (IGZ), 14979 Grossbeeren, Germany; NutriAct-Competence Cluster Nutrition Research Berlin-Potsdam, 14458 Nuthetal, Germany
| | - Tilman Grune
- Department of Molecular Toxicology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), 14558 Nuthetal, Germany; Institute of Nutrition, University of Potsdam, 14558 Nuthetal, Germany; German Center for Diabetes Research (DZD), 85764 München-Neuherberg, Germany; German Center for Cardiovascular Research (DZHK), 10117 Berlin, Germany; NutriAct-Competence Cluster Nutrition Research Berlin-Potsdam, 14458 Nuthetal, Germany.
| |
Collapse
|
|
12
|
Chen JH, Lin X, Bu C, Zhang X. Role of advanced glycation end products in mobility and considerations in possible dietary and nutritional intervention strategies. Nutr Metab (Lond) 2018; 15:72. [PMID: 30337945 PMCID: PMC6180645 DOI: 10.1186/s12986-018-0306-7] [Citation(s) in RCA: 119] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2018] [Accepted: 09/21/2018] [Indexed: 02/08/2023] Open
Abstract
Advanced glycation end products (AGEs), a group of compounds that are formed by non-enzymatic reactions between carbonyl groups of reducing sugars and free amino groups of proteins, lipids or nucleic acids, can be obtained exogenously from diet or formed endogenously within the body. AGEs accumulate intracellularly and extracellularly in all tissues and body fluids and can cross-link with other proteins and thus affect their normal functions. Furthermore, AGEs can interact with specific cell surface receptors and hence alter cell intracellular signaling, gene expression, the production of reactive oxygen species and the activation of several inflammatory pathways. High levels of AGEs in diet as well as in tissues and the circulation are pathogenic to a wide range of diseases. With respect to mobility, AGEs accumulate in bones, joints and skeletal muscles, playing important roles in the development of osteoporosis, osteoarthritis, and sarcopenia with aging. This report covered the related pathological mechanisms and the potential pharmaceutical and dietary intervention strategies in reducing systemic AGEs. More prospective studies are needed to determine whether elevated serum AGEs and/or skin autofluorescence predict a decline in measures of mobility. In addition, human intervention studies are required to investigate the beneficial effects of exogenous AGEs inhibitors on mobility outcomes.
Collapse
Affiliation(s)
- Jie-Hua Chen
- Science and Technology Centre, By-Health Co. Ltd, No. 3 Kehui 3rd Street, No. 99 Kexue Avenue Central, Science City, Luogang District, Guangzhou, 510000 China
| | - Xu Lin
- CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031 China
| | - Cuihong Bu
- Science and Technology Centre, By-Health Co. Ltd, No. 3 Kehui 3rd Street, No. 99 Kexue Avenue Central, Science City, Luogang District, Guangzhou, 510000 China
| | - Xuguang Zhang
- Science and Technology Centre, By-Health Co. Ltd, No. 3 Kehui 3rd Street, No. 99 Kexue Avenue Central, Science City, Luogang District, Guangzhou, 510000 China
| |
Collapse
|
|
13
|
Banevicius M, Vilkeviciute A, Kriauciuniene L, Liutkeviciene R, Deltuva VP. The Association Between Variants of Receptor for Advanced Glycation End Products (RAGE) Gene Polymorphisms and Age-Related Macular Degeneration. Med Sci Monit 2018; 24:190-199. [PMID: 29317590 PMCID: PMC5771184 DOI: 10.12659/msm.905311] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023] Open
Abstract
Background Age-related macular degeneration (AMD) is the leading cause of blindness in people aged 65 years and older in developed countries. The pathogenesis of AMD has been linked to mechanisms involving inflammation, oxidative stress, and basal laminar deposit formation between retinal pigment epithelium (RPE) cells and the basal membrane, caused by advanced glycation end products (AGEs). AGEs are implicated in the pathogenesis of AMD through the AGE-and receptor for AGE (RAGE) interaction, which can be altered by polymorphisms of the RAGE gene. We examined RAGE rs1800624 and rs1800625 gene polymorphisms contributing to AMD development. Material/Methods The study enrolled 300 patients with early AMD, 300 patients with exudative AMD, and 800 healthy controls. The genotyping was carried out using the RT-PCR method. Results The analysis of two single nucleotide polymorphisms (SNPs) in the RAGE gene showed that rs1800624 was associated with a 1.6-fold decreased risk for exudative AMD under the dominant model after adjustment for age (OR=0.616; 95% CI: 0.394–0.963; p=0.034) and each copy of allele T at rs1800624 was associated with a 1.4-fold decreased risk for exudative AMD development under the additive model after adjustment for age (OR=0.701; 95% CI: 0.510–0.962; p=0.028). Analysis revealed that the rs1800625 allele G at rs1800625 was associated with a 1.5-fold increased risk for exudative AMD after adjustment for age (OR=1.545; 95% CI: 1.003–2.379; p=0.048). These results suggested that the allele G at rs1800625 was a risk-allele for exudative AMD development. In haplotype analysis, A-G haplotype was significantly more frequently observed in exudative AMD patients compared to healthy controls (3.3% versus 1.4%, p=0.035). Conclusions We revealed a significant association between RAGE gene rs1800624 and rs1800625 polymorphisms and AMD risk. We considered T allele at rs1800624 to be protective against AMD development, while allele G at rs1800625 was considered to be a marker of poor prognosis in AMD development.
Collapse
Affiliation(s)
- Mantas Banevicius
- Department of Ophthalmology, Lithuanian University of Health Sciences, Medical Academy, Kaunas, Lithuania
| | - Alvita Vilkeviciute
- Neuroscience Institute, Lithuanian University of Health Sciences, Medical Academy, Kaunas, Lithuania
| | - Loresa Kriauciuniene
- Department of Ophthalmology, Lithuanian University of Health Sciences, Medical Academy, Kaunas, Lithuania.,Neuroscience Institute, Lithuanian University of Health Sciences, Medical Academy, Kaunas, Lithuania
| | - Rasa Liutkeviciene
- Department of Ophthalmology, Lithuanian University of Health Sciences, Medical Academy, Kaunas, Lithuania.,Neuroscience Institute, Lithuanian University of Health Sciences, Medical Academy, Kaunas, Lithuania
| | - Vytenis Pranas Deltuva
- Neuroscience Institute, Lithuanian University of Health Sciences, Medical Academy, Kaunas, Lithuania
| |
Collapse
|
|
14
|
Delgado-Andrade C. Carboxymethyl-lysine: thirty years of investigation in the field of AGE formation. Food Funct 2016; 7:46-57. [PMID: 26462729 DOI: 10.1039/c5fo00918a] [Citation(s) in RCA: 114] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
In 1985 carboxymethyl-lysine (CML), the first glycoxidation product, was discovered by Dr Ahmed while trying to identify the major products formed in reactions of glucose with lysine under physiological conditions. From that moment, a significant number of researchers have joined efforts to study its formation routes both in foods and in living beings, and the possibility of the existence of an additive action between food-occurring and in vivo produced CML and to explore all the implications associated with its appearance in the biological systems, regardless of its origin. This review presents interesting information on the latest advances in the research on CML sources, mitigation strategies, intake, metabolism and body fluid and tissue delivery, its possible in vivo synergy with highly modified advanced glycation end products-protein, and the physio-pathological implications derived from the presence of this compound in body fluids and tissues.
Collapse
Affiliation(s)
- Cristina Delgado-Andrade
- Department of Physiology and Biochemistry of Animal Nutrition, Estación Experimental del Zaidín (EEZ-CSIC), 18100, Granada, Spain.
| |
Collapse
|
|
15
|
Hunt WR, Helfman BR, McCarty NA, Hansen JM. Advanced glycation end products are elevated in cystic fibrosis-related diabetes and correlate with worse lung function. J Cyst Fibros 2016; 15:681-8. [DOI: 10.1016/j.jcf.2015.12.011] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2015] [Revised: 11/09/2015] [Accepted: 12/14/2015] [Indexed: 11/27/2022]
|
|
16
|
Guerrero N, Bunout D, Hirsch S, Barrera G, Leiva L, Henríquez S, De la Maza MP. Premature loss of muscle mass and function in type 2 diabetes. Diabetes Res Clin Pract 2016; 117:32-8. [PMID: 27329020 DOI: 10.1016/j.diabres.2016.04.011] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2015] [Revised: 03/22/2016] [Accepted: 04/15/2016] [Indexed: 12/25/2022]
Abstract
INTRODUCTION Muscle mass and function are among the most relevant factors that contribute to an optimal quality of life, and are strong predictors of mortality in the elderly. Loss of lean tissues and deterioration of muscle function have been described as one of the many complications of type 2 diabetes mellitus (DM2), but most studies do not isolate age as an intervening factor. AIM To study whether adult DM2 patients up to 60years of age have decreased muscle mass and function compared with healthy non-diabetic (ND) subjects of similar age. METHODOLOGY Appendicular fat-free mass (ApFFM) by dual X-ray absorptiometry (DEXA), handgrip strength (HS), quadriceps strength (QS), 12 min walking capacity (12MW) and the Timed Up and Go test (TUG) were measured in 100 DM2 patients and 39 ND controls. Muscle quality, or the ratio between lean mass and muscle strength of upper and lower limbs, and the functional limitations associated with pain and stiffness assessed according to the Western Ontario and McMaster Universities Arthrosis Index (WOMAC) were also recorded. Specific tests were performed to rule out microvascular diabetic complications (retinal and peripheral nerves), metabolic control, kidney function and vitamin D status and examine their association with ApFFM and function. RESULTS ApFFM was significantly higher among DM2 female patients and lower among diabetic men. However opposite results were obtained when individual values were corrected for body mass index (BMI), specifically among women, who were more likely to be obese. As for muscle strength and global functionality tests, significantly better performances in TUG, 12MW, QS and HS were observed among ND subjects of both sexes. These differences prevailed even after excluding diabetic patients with microvascular complications as well as those with more than 10years of diabetes. Muscle quality was also significantly better among ND women. Higher scores of pain and stiffness in the WOMAC scale correlated with 12MW and TUG in both groups but did not correlate with ApFFM. CONCLUSIONS We found a clear deterioration of lean mass and muscle functions among adult DM2 patients of up to 60years old, independent of length of disease, metabolic control, vitamin D status and presence of microvascular complications and pain.
Collapse
Affiliation(s)
- N Guerrero
- Institute of Nutrition and Food Technology Dr. Fernando Monckeberg Barros (INTA), University of Chile, Chile
| | - D Bunout
- Institute of Nutrition and Food Technology Dr. Fernando Monckeberg Barros (INTA), University of Chile, Chile
| | - S Hirsch
- Institute of Nutrition and Food Technology Dr. Fernando Monckeberg Barros (INTA), University of Chile, Chile
| | - G Barrera
- Institute of Nutrition and Food Technology Dr. Fernando Monckeberg Barros (INTA), University of Chile, Chile
| | - L Leiva
- Institute of Nutrition and Food Technology Dr. Fernando Monckeberg Barros (INTA), University of Chile, Chile
| | - S Henríquez
- Institute of Nutrition and Food Technology Dr. Fernando Monckeberg Barros (INTA), University of Chile, Chile
| | - M P De la Maza
- Institute of Nutrition and Food Technology Dr. Fernando Monckeberg Barros (INTA), University of Chile, Chile.
| |
Collapse
|
|
17
|
Drenth H, Zuidema S, Bunt S, Bautmans I, van der Schans C, Hobbelen H. The Contribution of Advanced Glycation End product (AGE) accumulation to the decline in motor function. Eur Rev Aging Phys Act 2016; 13:3. [PMID: 26949420 PMCID: PMC4779236 DOI: 10.1186/s11556-016-0163-1] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2015] [Accepted: 03/01/2016] [Indexed: 12/23/2022] Open
Abstract
Diminishing motor function is commonly observed in the elderly population and is associated with a wide range of adverse health consequences. Advanced Glycation End products (AGE's) may contribute to age-related decline in the function of cells and tissues in normal ageing. Although the negative effect of AGE's on the biomechanical properties of musculoskeletal tissues and the central nervous system have been previously described, the evidence regarding the effect on motor function is fragmented, and a systematic review on this topic is lacking. Therefore, a systematic review was conducted from a total of eight studies describing AGE's related to physical functioning, physical performance, and musculoskeletal outcome which reveals a positive association between high AGE's levels and declined walking abilities, inferior ADL, decreased muscle properties (strength, power and mass) and increased physical frailty. Elevated AGE's levels might be an indication to initiate (early) treatment such as dietary advice, muscle strengthening exercises, and functional training to maintain physical functions. Further longitudinal observational and controlled trial studies are necessary to investigate a causal relationship, and to what extent, high AGE's levels are a contributing risk factor and potential biomarker for a decline in motor function as a component of the ageing process.
Collapse
Affiliation(s)
- Hans Drenth
- />Research Group Healthy Ageing, Allied Healthcare and Nursing, Hanze University of Applied Sciences, PO Box 3109, 9701 DC Groningen, The Netherlands
- />Zuid Oost Zorg, Organisation for Elderly Care. Burg, Wuiteweg 140, 9203 KP Drachten, The Netherlands
| | - Sytse Zuidema
- />Department of General Practice, University of Groningen, University Medical Center Groningen, PO Box 196 9700 AD, Groningen, HPC FA21 The Netherlands
| | - Steven Bunt
- />Research Group Healthy Ageing, Allied Healthcare and Nursing, Hanze University of Applied Sciences, PO Box 3109, 9701 DC Groningen, The Netherlands
| | - Ivan Bautmans
- />Frailty in Ageing Research Group and Gerontology Department, Free University of Brussels, Laarbeeklaan 103, B-1090 Brussels, Belgium
| | - Cees van der Schans
- />Research Group Healthy Ageing, Allied Healthcare and Nursing, Hanze University of Applied Sciences, PO Box 3109, 9701 DC Groningen, The Netherlands
| | - Hans Hobbelen
- />Research Group Healthy Ageing, Allied Healthcare and Nursing, Hanze University of Applied Sciences, PO Box 3109, 9701 DC Groningen, The Netherlands
| |
Collapse
|
|
18
|
Mastrocola R, Nigro D, Chiazza F, Medana C, Dal Bello F, Boccuzzi G, Collino M, Aragno M. Fructose-derived advanced glycation end-products drive lipogenesis and skeletal muscle reprogramming via SREBP-1c dysregulation in mice. Free Radic Biol Med 2016; 91:224-35. [PMID: 26721591 DOI: 10.1016/j.freeradbiomed.2015.12.022] [Citation(s) in RCA: 54] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2015] [Revised: 12/07/2015] [Accepted: 12/19/2015] [Indexed: 12/21/2022]
Abstract
Advanced Glycation End-Products (AGEs) have been recently related to the onset of metabolic diseases and related complications. Moreover, recent findings indicate that AGEs can endogenously be formed by high dietary sugars, in particular by fructose which is widely used as added sweetener in foods and drinks. The aim of the present study was to investigate the impact of a high-fructose diet and the causal role of fructose-derived AGEs in mice skeletal muscle morphology and metabolism. C57Bl/6J mice were fed a standard diet (SD) or a 60% fructose diet (HFRT) for 12 weeks. Two subgroups of SD and HFRT mice received the anti-glycative compound pyridoxamine (150 mg/kg/day) in the drinking water. At the end of protocol high levels of AGEs were detected in both plasma and gastrocnemius muscle of HFRT mice associated to impaired expression of AGE-detoxifying AGE-receptor 1. In gastrocnemius, AGEs upregulated the lipogenesis by multiple interference on SREBP-1c through downregulation of the SREBP-inhibiting enzyme SIRT-1 and increased glycation of the SREBP-activating protein SCAP. The AGEs-induced SREBP-1c activation affected the expression of myogenic regulatory factors leading to alterations in fiber type composition, associated with reduced mitochondrial efficiency and muscular strength. Interestingly, pyridoxamine inhibited AGEs generation, thus counteracting all the fructose-induced alterations. The unsuspected involvement of diet-derived AGEs in muscle metabolic derangements and proteins reprogramming opens new perspectives in pathogenic mechanisms of metabolic diseases.
Collapse
Affiliation(s)
- R Mastrocola
- Department of Clinical and Biological Sciences, University of Turin, Italy.
| | - D Nigro
- Department of Clinical and Biological Sciences, University of Turin, Italy
| | - F Chiazza
- Department of Drug Science and Technology, University of Turin, Italy
| | - C Medana
- Department of Molecular Biotechnology and Health Sciences, University of Turin, Italy
| | - F Dal Bello
- Department of Molecular Biotechnology and Health Sciences, University of Turin, Italy
| | - G Boccuzzi
- Department of Medical Sciences, University of Turin, Italy
| | - M Collino
- Department of Drug Science and Technology, University of Turin, Italy
| | - M Aragno
- Department of Clinical and Biological Sciences, University of Turin, Italy
| |
Collapse
|
|
19
|
Ottum MS, Mistry AM. Advanced glycation end-products: modifiable environmental factors profoundly mediate insulin resistance. J Clin Biochem Nutr 2015; 57:1-12. [PMID: 26236094 PMCID: PMC4512899 DOI: 10.3164/jcbn.15-3] [Citation(s) in RCA: 55] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2015] [Accepted: 04/13/2015] [Indexed: 12/25/2022] Open
Abstract
Advanced glycation end-products are toxic by-products of metabolism and are also acquired from high-temperature processed foods. They promote oxidative damage to proteins, lipids and nucleotides. Aging and chronic diseases are strongly associated with markers for oxidative stress, especially advanced glycation end-products, and resistance to peripheral insulin-mediated glucose uptake. Modifiable environmental factors including high levels of refined and simple carbohydrate diets, hypercaloric diets and sedentary lifestyles drive endogenous formation of advanced glycation end-products via accumulation of highly reactive glycolysis intermediates and activation of the polyol/aldose reductase pathway producing high intracellular fructose. High advanced glycation end-products overwhelm innate defenses of enzymes and receptor-mediated endocytosis and promote cell damage via the pro-inflammatory and pro-oxidant receptor for advanced glycation end-products. Oxidative stress disturbs cell signal transduction, especially insulin-mediated metabolic responses. Here we review emerging evidence that restriction of dietary advanced glycation end-products significantly reduces total systemic load and insulin resistance in animals and humans in diabetes, polycystic ovary syndrome, healthy populations and dementia. Of clinical importance, this insulin sensitizing effect is independent of physical activity, caloric intake and adiposity level.
Collapse
Affiliation(s)
- Mona S Ottum
- Dietetics and Human Nutrition Program, 318 Marshall Building, Eastern Michigan University, Ypsilanti, MI 48197, USA
| | - Anahita M Mistry
- Dietetics and Human Nutrition Program, 318 Marshall Building, Eastern Michigan University, Ypsilanti, MI 48197, USA
| |
Collapse
|
|
20
|
de la Maza MP, Rodriguez JM, Hirsch S, Leiva L, Barrera G, Bunout D. Skeletal muscle ceramide species in men with abdominal obesity. J Nutr Health Aging 2015; 19:389-96. [PMID: 25809802 DOI: 10.1007/s12603-014-0548-7] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Obesity is a risk factor for diabetes and its consequences, including accelerated ageing and mortality. The underlying factor could be accumulation of certain lipid moieties, such as ceramides (CER) and diacylgycerol (DAG) within muscle tissue, which are known to promote insulin resistance (IR), induce inflammation and oxidative injury, ultimately altering muscle function. AIM First, to study the relationship between body composition and age (independent variables) with skeletal muscle accumulation of lipid species, oxidative injury and strength. Second, to analyze the relationship between muscle tissue metabolites and insulin resistance, inflammation and lymphocyte telomere length, the latter as an indicator of ageing. METHODOLOGY The sample included 56 healthy sedentary males, scheduled for inguinal hernia surgery, aged 27 to 80 y. Each individual was subject to anthropometric measurements, body composition assessment through radiologic densitometry (DEXA), measurement of handgrip and quadriceps strength, serum biochemical parameters (lipoproteins, creatinine, high sensitivity C reactive protein [hsCRP], fasting and post glucose insulin and glucose concentrations for calculation of IR through the Matsuda and HOMA-IR indexes), and extraction of peripheral leukocytes for measurement of telomere length. During the surgical procedure, a sample of muscle tissue was obtained (anterior abdominal oblique) in order to measure CER and DAG (and sub species according to chain length and saturation) by mass spectrometry, 4 hydroxy-2-nonenal adducts (4-HNE) using electron microscopy immunohistochemistry, and carboxymethyl-lisine (CML) by immunohistochemistry, the latter as indicators of oxidative stress (OS). RESULTS Body mass index (BMI) of twenty six individuals was > 25 k/m2, while BMI of 7 was > 30 k/m2. Overweight/obese individuals, did not exhibit differences in skeletal muscle lipid metabolites, however total CER and specific long chain CER sub-species (20 and 22 carbon) increased significantly among individuals with a central fat distribution (n = 14) as well as in glucose intolerant subjects (n =23). A negative association was found between mononuclear leukocyte telomere length and 20 and 22 carbon CER (rho = - 0.4 and -0.5 0 p < 0.05). Muscle strength was not associated with any of the measured muscle metabolites or markers of OS. A multiple regression analysis accepted central abdominal fat and telomere length as significant predictors of CER (R2 = 0.28). CONCLUSIONS An association was found between accumulation of specific ceramide species in muscle tissue and abdominal obesity, glucose intolerance and shortening of leukocyte telomeres, although not with muscle oxidative injury or dysfunction.
Collapse
Affiliation(s)
- M P de la Maza
- Maria Pia de la Maza, Institute of Nutrition and Food Technology, Human Nutrition, El Libano 5524, Santiago, 7830490, Chile, Tel: 56229781502, mobile: 56988894245, Fax: 56222214030,
| | | | | | | | | | | |
Collapse
|
|
21
|
Van Puyvelde K, Mets T, Njemini R, Beyer I, Bautmans I. Effect of advanced glycation end product intake on inflammation and aging: a systematic review. Nutr Rev 2014; 72:638-50. [PMID: 25231200 DOI: 10.1111/nure.12141] [Citation(s) in RCA: 84] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Aging is associated with a chronic low-grade inflammatory status that contributes to chronic diseases such as age-related muscle wasting, kidney disease, and diabetes mellitus. Since advanced glycation end products (AGEs) are known to be proinflammatory, this systematic review examined the relation between the dietary intake of AGEs and inflammatory processes. The PubMed and Web of Science databases were screened systematically. Seventeen relevant studies in humans or animals were included. The intervention studies in humans showed mainly a decrease in inflammation in subjects on a low-AGE diet, while an increase in inflammation in subjects on a high-AGE diet was less apparent. About half of the observational studies found a relationship between inflammatory processes and AGEs in food. When the results are considered together, the dietary intake of AGEs appears to be related to inflammatory status and the level of circulating AGEs. Moreover, limiting AGE intake may lead to a decrease in inflammation and chronic diseases related to inflammatory status. Most of the trials were conducted in patients with chronic kidney disease or diabetes, and thus additional studies in healthy individuals are needed. Further investigation is needed to elucidate the effects of lifetime exposure of dietary AGEs on aging and health.
Collapse
Affiliation(s)
- Katrien Van Puyvelde
- Frailty in Ageing (FRIA) Research Group and Gerontology Department, Vrije Universiteit Brussel, Brussels, Belgium; Department of Geriatric Medicine, Universitair Ziekenhuis Brussel, Brussels, Belgium
| | | | | | | | | |
Collapse
|
|
22
|
Serrão PRMS, Vasilceac FA, Gramani-Say K, Lessi GC, Reiff RBM, Mattiello-Sverzut AC, Mattiello SM. Expression of receptors of advanced glycation end product (RAGE) and types I, III and IV collagen in the vastus lateralis muscle of men in early stages of knee osteoarthritis. Connect Tissue Res 2014; 55:331-8. [PMID: 25039336 DOI: 10.3109/03008207.2014.947368] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
Alterations in the contractile and non-contractile proteins of the skeletal muscle may reduce muscle function in knee osteoarthritis (OA), and the formation and accumulation of advanced glycation end products, particularly in collagen, can influence the quality of these muscle proteins. The objective of this study was to evaluate the reactivity of types I, III and IV collagen and the expression and localization of receptor for advanced glycation end products (RAGE) in the vastus lateralis (VL) muscle in early stages of knee OA. The hypothesis was that these patients present a higher expression of RAGE and increased immunoreactivity in the collagen. Thirty-five men were divided into two groups: the control group (CG; n = 17) and the osteoarthritis group (OAG; n = 18). All participants were submitted to a biopsy of the VL. The muscle samples were analyzed by immunohistochemistry for collagen and for RAGE and laminin. The expression of RAGE was counted (intracellular, extracellular and total). Student's t-test for independent samples and Mann-Whitney U test were used for the RAGE's intergroup analysis (α ≤ 0.05). A semiquantitative analysis was performed to assess the collagen reactivity. No significant differences were observed in the intracellular, extracellular or total localization of RAGE (p > 0.05). Higher immunoreactivity was observed in the OAG for all types of collagen, with more reactivity for collagen III and IV. We concluded that in the initial stages of knee OA, no differences were observed for RAGE levels between the groups. However, the OAG's higher collagen expression may represent adaptations for reducing muscle stiffness and avoiding injury.
Collapse
|
|
23
|
Gaens KHJ, Goossens GH, Niessen PM, van Greevenbroek MM, van der Kallen CJH, Niessen HW, Rensen SS, Buurman WA, Greve JWM, Blaak EE, van Zandvoort MA, Bierhaus A, Stehouwer CDA, Schalkwijk CG. Nε-(carboxymethyl)lysine-receptor for advanced glycation end product axis is a key modulator of obesity-induced dysregulation of adipokine expression and insulin resistance. Arterioscler Thromb Vasc Biol 2014; 34:1199-208. [PMID: 24723555 DOI: 10.1161/atvbaha.113.302281] [Citation(s) in RCA: 156] [Impact Index Per Article: 14.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
OBJECTIVE Dysregulation of inflammatory adipokines by the adipose tissue plays an important role in obesity-associated insulin resistance. Pathways leading to this dysregulation remain largely unknown. We hypothesized that the receptor for advanced glycation end products (RAGE) and the ligand N(ε)-(carboxymethyl)lysine (CML) are increased in adipose tissue and, moreover, that activation of the CML-RAGE axis plays an important role in obesity-associated inflammation and insulin resistance. APPROACH AND RESULTS In this study, we observed a strong CML accumulation and increased expression of RAGE in adipose tissue in obesity. We confirmed in cultured human preadipocytes that adipogenesis is associated with increased levels of CML and RAGE. Moreover, CML induced a dysregulation of inflammatory adipokines in adipocytes via a RAGE-dependent pathway. To test the role of RAGE in obesity-associated inflammation further, we constructed an obese mouse model that is deficient for RAGE (ie, RAGE(-/-)/Leptr(Db-/-) mice). RAGE(-/-)/Leptr(Db-/-) mice displayed an improved inflammatory profile and glucose homeostasis when compared with RAGE(+/+)/Leptr(Db-/-) mice. In addition, CML was trapped in adipose tissue in RAGE(+/+)/Leptr(Db-/-) mice but not in RAGE(-/-)/Leptr(Db-/-). RAGE-mediated trapping in adipose tissue provides a mechanism underlying CML accumulation in adipose tissue and explaining decreased CML plasma levels in obese subjects. Decreased CML plasma levels in obese individuals were strongly associated with insulin resistance. CONCLUSIONS RAGE-mediated CML accumulation in adipose tissue and the activation of the CML-RAGE axis are important mechanisms involved in the dysregulation of adipokines in obesity, thereby contributing to the development of obesity-associated insulin resistance.
Collapse
Affiliation(s)
- Katrien H J Gaens
- From the Department of Internal Medicine and the Laboratory of Metabolism and Vascular Medicine (K.H.J.G., P.M.N., M.M.v.G., C.J.H.v.d.K., C.D.A.S., C.G.S.), Cardiovascular Research Institute Maastricht (K.H.J.G., P.M.N., M.M.v.G., C.J.H.v.d.K., M.A.v.Z., C.D.A.S., C.G.S.), Department of Human Biology (G.H.G., E.E.B.), NUTRIM School for Nutrition, Toxicology, and Metabolism (G.H.G., S.S.R., W.A.B., J.W.M.G., E.E.B.), Department of General Surgery (S.S.R., W.A.B., J.W.M.G.), and Department of Biomedical Engineering (M.A.v.Z.), Maastricht University Medical Center, Maastricht, The Netherlands; Department of Pathology and Cardiac Surgery, Institute for Cardiovascular Research, Vrije Universiteit Medical Center, Amsterdam, The Netherlands (H.W.N.); and Department of Medicine and Clinical Chemistry, University of Heidelberg, Heidelberg, Germany (A.B.)
| | - Gijs H Goossens
- From the Department of Internal Medicine and the Laboratory of Metabolism and Vascular Medicine (K.H.J.G., P.M.N., M.M.v.G., C.J.H.v.d.K., C.D.A.S., C.G.S.), Cardiovascular Research Institute Maastricht (K.H.J.G., P.M.N., M.M.v.G., C.J.H.v.d.K., M.A.v.Z., C.D.A.S., C.G.S.), Department of Human Biology (G.H.G., E.E.B.), NUTRIM School for Nutrition, Toxicology, and Metabolism (G.H.G., S.S.R., W.A.B., J.W.M.G., E.E.B.), Department of General Surgery (S.S.R., W.A.B., J.W.M.G.), and Department of Biomedical Engineering (M.A.v.Z.), Maastricht University Medical Center, Maastricht, The Netherlands; Department of Pathology and Cardiac Surgery, Institute for Cardiovascular Research, Vrije Universiteit Medical Center, Amsterdam, The Netherlands (H.W.N.); and Department of Medicine and Clinical Chemistry, University of Heidelberg, Heidelberg, Germany (A.B.)
| | - Petra M Niessen
- From the Department of Internal Medicine and the Laboratory of Metabolism and Vascular Medicine (K.H.J.G., P.M.N., M.M.v.G., C.J.H.v.d.K., C.D.A.S., C.G.S.), Cardiovascular Research Institute Maastricht (K.H.J.G., P.M.N., M.M.v.G., C.J.H.v.d.K., M.A.v.Z., C.D.A.S., C.G.S.), Department of Human Biology (G.H.G., E.E.B.), NUTRIM School for Nutrition, Toxicology, and Metabolism (G.H.G., S.S.R., W.A.B., J.W.M.G., E.E.B.), Department of General Surgery (S.S.R., W.A.B., J.W.M.G.), and Department of Biomedical Engineering (M.A.v.Z.), Maastricht University Medical Center, Maastricht, The Netherlands; Department of Pathology and Cardiac Surgery, Institute for Cardiovascular Research, Vrije Universiteit Medical Center, Amsterdam, The Netherlands (H.W.N.); and Department of Medicine and Clinical Chemistry, University of Heidelberg, Heidelberg, Germany (A.B.)
| | - Marleen M van Greevenbroek
- From the Department of Internal Medicine and the Laboratory of Metabolism and Vascular Medicine (K.H.J.G., P.M.N., M.M.v.G., C.J.H.v.d.K., C.D.A.S., C.G.S.), Cardiovascular Research Institute Maastricht (K.H.J.G., P.M.N., M.M.v.G., C.J.H.v.d.K., M.A.v.Z., C.D.A.S., C.G.S.), Department of Human Biology (G.H.G., E.E.B.), NUTRIM School for Nutrition, Toxicology, and Metabolism (G.H.G., S.S.R., W.A.B., J.W.M.G., E.E.B.), Department of General Surgery (S.S.R., W.A.B., J.W.M.G.), and Department of Biomedical Engineering (M.A.v.Z.), Maastricht University Medical Center, Maastricht, The Netherlands; Department of Pathology and Cardiac Surgery, Institute for Cardiovascular Research, Vrije Universiteit Medical Center, Amsterdam, The Netherlands (H.W.N.); and Department of Medicine and Clinical Chemistry, University of Heidelberg, Heidelberg, Germany (A.B.)
| | - Carla J H van der Kallen
- From the Department of Internal Medicine and the Laboratory of Metabolism and Vascular Medicine (K.H.J.G., P.M.N., M.M.v.G., C.J.H.v.d.K., C.D.A.S., C.G.S.), Cardiovascular Research Institute Maastricht (K.H.J.G., P.M.N., M.M.v.G., C.J.H.v.d.K., M.A.v.Z., C.D.A.S., C.G.S.), Department of Human Biology (G.H.G., E.E.B.), NUTRIM School for Nutrition, Toxicology, and Metabolism (G.H.G., S.S.R., W.A.B., J.W.M.G., E.E.B.), Department of General Surgery (S.S.R., W.A.B., J.W.M.G.), and Department of Biomedical Engineering (M.A.v.Z.), Maastricht University Medical Center, Maastricht, The Netherlands; Department of Pathology and Cardiac Surgery, Institute for Cardiovascular Research, Vrije Universiteit Medical Center, Amsterdam, The Netherlands (H.W.N.); and Department of Medicine and Clinical Chemistry, University of Heidelberg, Heidelberg, Germany (A.B.)
| | - Hans W Niessen
- From the Department of Internal Medicine and the Laboratory of Metabolism and Vascular Medicine (K.H.J.G., P.M.N., M.M.v.G., C.J.H.v.d.K., C.D.A.S., C.G.S.), Cardiovascular Research Institute Maastricht (K.H.J.G., P.M.N., M.M.v.G., C.J.H.v.d.K., M.A.v.Z., C.D.A.S., C.G.S.), Department of Human Biology (G.H.G., E.E.B.), NUTRIM School for Nutrition, Toxicology, and Metabolism (G.H.G., S.S.R., W.A.B., J.W.M.G., E.E.B.), Department of General Surgery (S.S.R., W.A.B., J.W.M.G.), and Department of Biomedical Engineering (M.A.v.Z.), Maastricht University Medical Center, Maastricht, The Netherlands; Department of Pathology and Cardiac Surgery, Institute for Cardiovascular Research, Vrije Universiteit Medical Center, Amsterdam, The Netherlands (H.W.N.); and Department of Medicine and Clinical Chemistry, University of Heidelberg, Heidelberg, Germany (A.B.)
| | - Sander S Rensen
- From the Department of Internal Medicine and the Laboratory of Metabolism and Vascular Medicine (K.H.J.G., P.M.N., M.M.v.G., C.J.H.v.d.K., C.D.A.S., C.G.S.), Cardiovascular Research Institute Maastricht (K.H.J.G., P.M.N., M.M.v.G., C.J.H.v.d.K., M.A.v.Z., C.D.A.S., C.G.S.), Department of Human Biology (G.H.G., E.E.B.), NUTRIM School for Nutrition, Toxicology, and Metabolism (G.H.G., S.S.R., W.A.B., J.W.M.G., E.E.B.), Department of General Surgery (S.S.R., W.A.B., J.W.M.G.), and Department of Biomedical Engineering (M.A.v.Z.), Maastricht University Medical Center, Maastricht, The Netherlands; Department of Pathology and Cardiac Surgery, Institute for Cardiovascular Research, Vrije Universiteit Medical Center, Amsterdam, The Netherlands (H.W.N.); and Department of Medicine and Clinical Chemistry, University of Heidelberg, Heidelberg, Germany (A.B.)
| | - Wim A Buurman
- From the Department of Internal Medicine and the Laboratory of Metabolism and Vascular Medicine (K.H.J.G., P.M.N., M.M.v.G., C.J.H.v.d.K., C.D.A.S., C.G.S.), Cardiovascular Research Institute Maastricht (K.H.J.G., P.M.N., M.M.v.G., C.J.H.v.d.K., M.A.v.Z., C.D.A.S., C.G.S.), Department of Human Biology (G.H.G., E.E.B.), NUTRIM School for Nutrition, Toxicology, and Metabolism (G.H.G., S.S.R., W.A.B., J.W.M.G., E.E.B.), Department of General Surgery (S.S.R., W.A.B., J.W.M.G.), and Department of Biomedical Engineering (M.A.v.Z.), Maastricht University Medical Center, Maastricht, The Netherlands; Department of Pathology and Cardiac Surgery, Institute for Cardiovascular Research, Vrije Universiteit Medical Center, Amsterdam, The Netherlands (H.W.N.); and Department of Medicine and Clinical Chemistry, University of Heidelberg, Heidelberg, Germany (A.B.)
| | - Jan Willem M Greve
- From the Department of Internal Medicine and the Laboratory of Metabolism and Vascular Medicine (K.H.J.G., P.M.N., M.M.v.G., C.J.H.v.d.K., C.D.A.S., C.G.S.), Cardiovascular Research Institute Maastricht (K.H.J.G., P.M.N., M.M.v.G., C.J.H.v.d.K., M.A.v.Z., C.D.A.S., C.G.S.), Department of Human Biology (G.H.G., E.E.B.), NUTRIM School for Nutrition, Toxicology, and Metabolism (G.H.G., S.S.R., W.A.B., J.W.M.G., E.E.B.), Department of General Surgery (S.S.R., W.A.B., J.W.M.G.), and Department of Biomedical Engineering (M.A.v.Z.), Maastricht University Medical Center, Maastricht, The Netherlands; Department of Pathology and Cardiac Surgery, Institute for Cardiovascular Research, Vrije Universiteit Medical Center, Amsterdam, The Netherlands (H.W.N.); and Department of Medicine and Clinical Chemistry, University of Heidelberg, Heidelberg, Germany (A.B.)
| | - Ellen E Blaak
- From the Department of Internal Medicine and the Laboratory of Metabolism and Vascular Medicine (K.H.J.G., P.M.N., M.M.v.G., C.J.H.v.d.K., C.D.A.S., C.G.S.), Cardiovascular Research Institute Maastricht (K.H.J.G., P.M.N., M.M.v.G., C.J.H.v.d.K., M.A.v.Z., C.D.A.S., C.G.S.), Department of Human Biology (G.H.G., E.E.B.), NUTRIM School for Nutrition, Toxicology, and Metabolism (G.H.G., S.S.R., W.A.B., J.W.M.G., E.E.B.), Department of General Surgery (S.S.R., W.A.B., J.W.M.G.), and Department of Biomedical Engineering (M.A.v.Z.), Maastricht University Medical Center, Maastricht, The Netherlands; Department of Pathology and Cardiac Surgery, Institute for Cardiovascular Research, Vrije Universiteit Medical Center, Amsterdam, The Netherlands (H.W.N.); and Department of Medicine and Clinical Chemistry, University of Heidelberg, Heidelberg, Germany (A.B.)
| | - Marc A van Zandvoort
- From the Department of Internal Medicine and the Laboratory of Metabolism and Vascular Medicine (K.H.J.G., P.M.N., M.M.v.G., C.J.H.v.d.K., C.D.A.S., C.G.S.), Cardiovascular Research Institute Maastricht (K.H.J.G., P.M.N., M.M.v.G., C.J.H.v.d.K., M.A.v.Z., C.D.A.S., C.G.S.), Department of Human Biology (G.H.G., E.E.B.), NUTRIM School for Nutrition, Toxicology, and Metabolism (G.H.G., S.S.R., W.A.B., J.W.M.G., E.E.B.), Department of General Surgery (S.S.R., W.A.B., J.W.M.G.), and Department of Biomedical Engineering (M.A.v.Z.), Maastricht University Medical Center, Maastricht, The Netherlands; Department of Pathology and Cardiac Surgery, Institute for Cardiovascular Research, Vrije Universiteit Medical Center, Amsterdam, The Netherlands (H.W.N.); and Department of Medicine and Clinical Chemistry, University of Heidelberg, Heidelberg, Germany (A.B.)
| | - Angelika Bierhaus
- From the Department of Internal Medicine and the Laboratory of Metabolism and Vascular Medicine (K.H.J.G., P.M.N., M.M.v.G., C.J.H.v.d.K., C.D.A.S., C.G.S.), Cardiovascular Research Institute Maastricht (K.H.J.G., P.M.N., M.M.v.G., C.J.H.v.d.K., M.A.v.Z., C.D.A.S., C.G.S.), Department of Human Biology (G.H.G., E.E.B.), NUTRIM School for Nutrition, Toxicology, and Metabolism (G.H.G., S.S.R., W.A.B., J.W.M.G., E.E.B.), Department of General Surgery (S.S.R., W.A.B., J.W.M.G.), and Department of Biomedical Engineering (M.A.v.Z.), Maastricht University Medical Center, Maastricht, The Netherlands; Department of Pathology and Cardiac Surgery, Institute for Cardiovascular Research, Vrije Universiteit Medical Center, Amsterdam, The Netherlands (H.W.N.); and Department of Medicine and Clinical Chemistry, University of Heidelberg, Heidelberg, Germany (A.B.)
| | - Coen D A Stehouwer
- From the Department of Internal Medicine and the Laboratory of Metabolism and Vascular Medicine (K.H.J.G., P.M.N., M.M.v.G., C.J.H.v.d.K., C.D.A.S., C.G.S.), Cardiovascular Research Institute Maastricht (K.H.J.G., P.M.N., M.M.v.G., C.J.H.v.d.K., M.A.v.Z., C.D.A.S., C.G.S.), Department of Human Biology (G.H.G., E.E.B.), NUTRIM School for Nutrition, Toxicology, and Metabolism (G.H.G., S.S.R., W.A.B., J.W.M.G., E.E.B.), Department of General Surgery (S.S.R., W.A.B., J.W.M.G.), and Department of Biomedical Engineering (M.A.v.Z.), Maastricht University Medical Center, Maastricht, The Netherlands; Department of Pathology and Cardiac Surgery, Institute for Cardiovascular Research, Vrije Universiteit Medical Center, Amsterdam, The Netherlands (H.W.N.); and Department of Medicine and Clinical Chemistry, University of Heidelberg, Heidelberg, Germany (A.B.)
| | - Casper G Schalkwijk
- From the Department of Internal Medicine and the Laboratory of Metabolism and Vascular Medicine (K.H.J.G., P.M.N., M.M.v.G., C.J.H.v.d.K., C.D.A.S., C.G.S.), Cardiovascular Research Institute Maastricht (K.H.J.G., P.M.N., M.M.v.G., C.J.H.v.d.K., M.A.v.Z., C.D.A.S., C.G.S.), Department of Human Biology (G.H.G., E.E.B.), NUTRIM School for Nutrition, Toxicology, and Metabolism (G.H.G., S.S.R., W.A.B., J.W.M.G., E.E.B.), Department of General Surgery (S.S.R., W.A.B., J.W.M.G.), and Department of Biomedical Engineering (M.A.v.Z.), Maastricht University Medical Center, Maastricht, The Netherlands; Department of Pathology and Cardiac Surgery, Institute for Cardiovascular Research, Vrije Universiteit Medical Center, Amsterdam, The Netherlands (H.W.N.); and Department of Medicine and Clinical Chemistry, University of Heidelberg, Heidelberg, Germany (A.B.).
| |
Collapse
|
|
24
|
Bunout D, Barrera G, de la Maza MP, Leiva L, Hirsch S. Effect of weight maintenance or gain in a 10 years period over telomere length, sirtuin 1 and 6 expression and carotid intima media thickness. J Hum Nutr Diet 2014; 28:155-64. [DOI: 10.1111/jhn.12231] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Affiliation(s)
- D. Bunout
- Institute of Nutrition and Food Technology; University of Chile; Santiago Chile
| | - G. Barrera
- Institute of Nutrition and Food Technology; University of Chile; Santiago Chile
| | - M. P. de la Maza
- Institute of Nutrition and Food Technology; University of Chile; Santiago Chile
| | - L. Leiva
- Institute of Nutrition and Food Technology; University of Chile; Santiago Chile
| | - S. Hirsch
- Institute of Nutrition and Food Technology; University of Chile; Santiago Chile
| |
Collapse
|
|
25
|
Xu L, Zang P, Feng B, Qian Q. Atorvastatin inhibits the expression of RAGE induced by advanced glycation end products on aortas in healthy Sprague-Dawley rats. Diabetol Metab Syndr 2014; 6:102. [PMID: 25279006 PMCID: PMC4180585 DOI: 10.1186/1758-5996-6-102] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2014] [Accepted: 09/10/2014] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Atorvastatin can downregulate the expression of receptor for advanced glycation end products (RAGE) in the aortas of diabetic rats. However, its effect on healthy rats remains unclear. The aim of this study was to observe the direct impact of atorvastatin on advanced glycation end products- (AGEs) induced RAGE expression in healthy Sprague Dawley (SD) rats. METHODS SD rats received AGE-BSA (20 mg/kg/day or 40 mg/kg/day), dual treatment (AGE-BSA 40 mg/kg/day and atorvastatin 20 mg/kg/day) or no treatment for 12 and 24 weeks, respectively. The deposition of AGEs and expression of RAGE in the animals' aortas were assessed by Quantitative RT-PCR, immunohistochemistry, and western-blot tests. Serum levels of AGEs were measured using ELISA. RESULTS AGE-BSA upregulated the serum level of AGEs, deposition of AGEs, and expression of RAGE in aortas in a time- and dose-dependent way that can accelerate the development and progression of atherosclerosis. These upregulations could be significantly attenuated by atorvastatin in the absence of its lipid-lowering effects. These data provide further evidence for the novo mechanism of atorvastatin's pleiotropic effect. CONCLUSION Atorvastatin has a direct inhibitory effect on AGEs-RAGE expression in healthy SD rats. These potential pleiotropic vasculoprotective effects are independent of effects on glucose and lipid control.
Collapse
Affiliation(s)
- Lei Xu
- />Department of Endocriology and Metabolic Disease, East Hospital, Tongji University School of Medicine, Shanghai, 200120 China
| | - Panpan Zang
- />Department of Endocriology, Shanghai Ninth People’s Hospital Affiliated Shanghai Jiaotong University School of Medicine, Shanghai, 200120 China
| | - Bo Feng
- />Department of Endocriology and Metabolic Disease, East Hospital, Tongji University School of Medicine, Shanghai, 200120 China
| | - Qiaohui Qian
- />Department of Endocriology, Shanghai Zhoupu Hospital, Shanghai, 200120 China
| |
Collapse
|
|
26
|
Mattiello-Sverzut AC, Petersen SG, Kjaer M, Mackey AL. Morphological adaptation of muscle collagen and receptor of advanced glycation end product (RAGE) in osteoarthritis patients with 12 weeks of resistance training: influence of anti-inflammatory or glucosamine treatment. Rheumatol Int 2013; 33:2215-24. [DOI: 10.1007/s00296-013-2698-z] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2012] [Accepted: 02/01/2013] [Indexed: 01/11/2023]
|
|
27
|
Gaens KHJ, Stehouwer CDA, Schalkwijk CG. Advanced glycation endproducts and its receptor for advanced glycation endproducts in obesity. Curr Opin Lipidol 2013; 24:4-11. [PMID: 23298958 DOI: 10.1097/mol.0b013e32835aea13] [Citation(s) in RCA: 109] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
PURPOSE OF REVIEW To highlight the potential importance of advanced glycation endproducts (AGEs) and advanced-lipoxidation endproducts (ALEs) in obesity and obesity-related complications, and the contribution of the receptor for advanced glycation endproducts (RAGE) and the glyoxylase defense system therein. RECENT FINDINGS Formation of AGEs/ALEs and its precursors, including methylglyoxal (MGO), are increased in conditions characterized by hyperglycemia, hyperlipidemia and enhanced oxidative stress. This metabolic profile is generally considered typical for obesity. Increased plasma and/or tissue levels of MGO and of specific AGEs/ALEs, such as N(ε)-(carboxymethyl)lysine (CML), in obesity have recently been described. In addition to increased formation, the suppressed defense system in obesity against AGEs/ALEs formation, that is, the glyoxylase system, will further contribute to AGEs/ALEs formation in obesity. AGEs/ALEs are not inert. In-vitro studies showed that AGEs induced the production of inflammatory mediators in adipocytes and macrophages via RAGE activation, which may subsequently contribute to the development of obesity-related complications. SUMMARY The recognition of an enhanced AGEs/ALEs formation in adipose tissue and the biological consequences thereof may lead to a further understanding of underlying mechanisms in dysregulated production of adipokines in obesity.
Collapse
Affiliation(s)
- Katrien H J Gaens
- Department of Internal Medicine, Maastricht University Medical Center, Maastricht, the Netherlands
| | | | | |
Collapse
|
|
28
|
Relationship of an advanced glycation end product, plasma carboxymethyl-lysine, with slow walking speed in older adults: the InCHIANTI study. Eur J Appl Physiol 2009; 108:191-5. [PMID: 19756703 DOI: 10.1007/s00421-009-1192-5] [Citation(s) in RCA: 75] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/27/2009] [Indexed: 01/09/2023]
Abstract
Advanced glycation end products (AGEs) are bioactive molecules found in foods and generated endogenously in the body. AGEs induce cross-linking of collagen and increase the stiffness of skeletal muscle and cartilage. We characterized the relationship between a plasma AGE, carboxymethyl-lysine (CML), and slow walking speed (lowest quintile of walking speed) in older adults. Walking speed over a 4 m course was assessed in 944 adults, aged >or=65 years, in the InCHIANTI study, a population-based study of aging and mobility disability conducted in two towns in Tuscany, Italy. Participants in the highest quartile of plasma CML were at higher risk of slow walking speed (Odds Ratio [O.R.] 1.56, 95% Confidence Interval [C.I.] 1.02-2.38, P = 0.04) compared to those in the lower three quartiles of plasma CML in a logistic regression models adjusting for age, education, cognitive function, smoking, and chronic diseases. After exclusion of participants with diabetes, participants in the highest quartile of plasma CML were at higher risk of slow walking speed (O.R. 1.87, 95% C.I. 1.15-3.04, P = 0.01) adjusting for the same covariates. In older community-dwelling adults, elevated plasma CML is independently associated with slow walking speed.
Collapse
|