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Metaflammation is low-grade inflammation triggered by chronic metabolic imbalance and caused by dysregulated metabolites in metabolic inflammatory syndrome (MIS), which includes four diseases: obesity, type 2 diabetes mellitus (T2DM), atherosclerosis (AS), and nonalcoholic fatty liver diseases (NAFLD, recently proposed to be replaced by metabolic dysfunction-associated steatotic liver disease, MASLD). These diseases exhibit apparent sex dimorphism as regards MIS. Estrogen not only plays a crucial role in gender differences in adults but also possesses an anti-inflammatory effect on many metabolic diseases. In this study, we present a prediction of the differential proteins and signal transduction of estrogen in MIS through network pharmacology and review the validated studies on obesity, T2DM, AS, and NAFLD. Subsequently, we compared them to obtain valuable targets, identify current gaps, and provide perspectives for future research on the mechanisms of estrogen in metaflammation. [ABSTRACT FROM AUTHOR]

Metaflammation is low-grade inflammation triggered by chronic metabolic imbalance and caused by dysregulated metabolites in metabolic inflammatory syndrome (MIS), which includes four diseases: obesity, type 2 diabetes mellitus (T2DM), atherosclerosis (AS), and nonalcoholic fatty liver diseases (NAFLD, recently proposed to be replaced by metabolic dysfunction-associated steatotic liver disease, MASLD). These diseases exhibit apparent sex dimorphism as regards MIS. Estrogen not only plays a crucial role in gender differences in adults but also possesses an anti-inflammatory effect on many metabolic diseases. In this study, we present a prediction of the differential proteins and signal transduction of estrogen in MIS through network pharmacology and review the validated studies on obesity, T2DM, AS, and NAFLD. Subsequently, we compared them to obtain valuable targets, identify current gaps, and provide perspectives for future research on the mechanisms of estrogen in metaflammation.

Qingsong Wang,1 Xiu-ling Zhou,2 Guang-hai Mei,3 Jiantao Wang,1 Zhongyu Yu,1 Yue Hu,1 Xinyu Guo,1 Hanyu Zhang,1 Xiaodie Xu,4 Chengfeng He,4 Jingchun Guo,4 Yinghong Tao,5 Houguang Zhou1 1Department of Geriatrics, Huashan Hospital, National Clinical Research Center for Aging and Medicine, Fudan University, Shanghai, 200040, People’s Republic of China; 2Department of Ultrasonics, Huashan Hospital, Fudan University, Shanghai, 200040, People’s Republic of China; 3Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, 200040, People’s Republic of China; 4National Key Laboratory of Medical Neurobiology, Institute of Brain Science, Fudan University, Shanghai, 200030, People’s Republic of China; 5Department of Medical Examination Center, Huashan Hospital, Fudan University, Shanghai, 200040, People’s Republic of ChinaCorrespondence: Houguang ZhouDepartment of Geriatrics of Huashan Hospital, National Clinical Research Center for Aging and Medicine, Fudan University, No. 24 Ward, Building 6, No.12 Middle WuLuMuQi Road, JingAn District, Shanghai, 200040, People’s Republic of ChinaTel +86-21-52887246Email zhouhouguang@huashan.org.cnYinghong TaoDepartment of Medical Examination Center of Huashan Hospital, Fudan University, Building 4, No. 12 Middle WuLuMuQi Road, JingAn District, Shanghai, 200040, People’s Republic of ChinaTel +86-21-52889087Email taoyinghong@huashan.org.cnAim: Metabolic inflammation syndrome (MIS) can lead to a series of complications, but its exact inflammatory mechanism is still unclear. The aim of this study was to explore the correlation between heparanase (HPA) and MIS, and the close relationship between HPA and other chronic low-grade inflammation index, such as C-reactive protein (CRP) and interleukin-6 (IL-6).Methods: A total of 105 patients with MIS in the physical examination population of Huashan Hospital affiliated to Fudan University from May to June 2018 were selected as the MIS group, and 52 patients who were relatively healthy during the same period were used as the control group. The basic clinical data of the selected candidates were collected, the levels of serum HPA, CRP and IL-6 were measured by ELISA, and the levels of blood glucose and blood lipids were also detected.Results: Compared with the control group, the levels of HPA, CRP, IL-6, FBG, HbA1C, and TG of MIS group were all significantly elevated (all P< 0.05), and HDL-C levels were considerably reduced (P< 0.05). Correlation analysis showed that there was a noticeably positive correlation between serum HPA level and CRP, IL-6 levels (P< 0.05).Conclusion: Higher HPA levels might play a certain role in the occurrence and development of MIS. There was a certain close correlation between serum HPA level and CRP and IL-6 levels, and which indicated that HPA was involved in the chronic low-grade inflammatory reaction process of MIS.Keywords: metabolic inflammatory syndrome, MIS, heparanase, HPA, C-reactive protein, CRP, interleukin-6, IL-6, chronic low-grade inflammation, CLGI

Objective To explore the risk factors of type 2 diabetes mellitus (T2DM) complicated with metabolic inflammatory syndrome (MIS). Methods According to the inclusion and exclusion criteria, 110 patients with T2DM were selected as the research objects. According to the presence or absence of metabolic inflammatory syndrome, they were divided into the control group and MIS group, with 53 cases in the control group and 57 cases in the MIS group. The influencing factors and risk factors for T2DM combined MIS were analyzed by Univariate analysis and Multivariate Logistic regression analysis method. Results Significant differences were found in the disease course, body mass index (BMI), waistto- hip ratio, serum low-density lipoprotein cholesterol, triglycerides (TG), free fatty acids, C-reactive protein (CRP), and total bilirubin (TB) levels between these two groups (all P<0. 05). Multivariate analysis showed that high BMI, waistto- hip ratio, and serum TG, TB, and CRP were independent risk factors for T2DM complicated with MIS (all P<0. 05). Conclusion High BMI, waist-to-hip ratio, and serum TG, TB, and CRP levels are risk factors for T2DM complicated with MIS. [ABSTRACT FROM AUTHOR]

Lina Ma,1,* Yanhong Xu,1,2,* Yaxin Zhang,1 Tong Ji,1 Yun Li1 1Department of Geriatrics, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing 100053, People’s Republic of China; 2Department of Geriatrics, Miyun Teaching Hospital of Capital Medical University, Beijing 101500, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lina MaDepartment of Geriatrics, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, #45 Changchun Street, Xicheng District, Beijing 100053, People’s Republic of ChinaEmail malina0883@126.comBackground: Metabolic inflammation plays an important role in the pathogenesis of atherosclerosis, type 2 diabetes, non-alcoholic fatty liver disease, and obesity. The above metabolic disorders often coexist and are closely related with systemic low-grade inflammation. Metabolic inflammatory syndrome (MIS), a cluster of these four metabolic disorders, is a novel concept that is thought to be a better predictor of coronary heart disease than metabolic syndrome. Adiponectin is an adipokine that increases insulin sensitivity and antioxidation as well as has an anti-atherosclerosis effect. It is unclear whether adiponectin is associated with MIS. The objective of this study was to assess whether circulating adiponectin can be used as an indicator for MIS in elderly adults.Methods: A total of 136 elderly inpatients were divided into two groups: the MIS group and the non-MIS group. Characteristics, inflammatory markers, blood lipid metabolism, insulin resistance, and circulating adiponectin levels were assessed and compared between the two groups. Logistic regression analysis was used to explore the association between the associated factors and MIS.Results: MIS patients were more likely to have a higher body mass index, have a higher fasting blood glucose level, be smokers, have fundus arteriosclerosis, have lower levels of adiponectin (4044.90 ± 3906.82 ng/mL vs 8503.89 ± 3523.89 ng/mL, p < 0.001), and have higher levels of inflammation (white blood cell and C-reactive protein) than non-MIS patients. Multiple factor analysis showed that lower adiponectin levels (OR = 22.937, p < 0.001) were independently associated with MIS. Adiponectin levels were lower in the vascular disease (2673.29 ± 1930.05 ng/mL vs 7194.38 ± 4615.83 ng/mL, p = 0.001), atherosclerosis (2374.14 [1496.41– 4263.90] ng/mL vs 6037.48 [3865.61– 10,373.60] ng/mL, p < 0.001), and type 2 diabetes (2391.73 [1386.41– 4069.68] ng/mL vs 8916.03 [5801.14– 12,724.45] ng/mL, p < 0.001) subgroups than in the non-MIS group.Conclusion: Lower adiponectin levels in serum are associated with MIS. Low adiponectin may be used as a biomarker for atherosclerosis in patients with MIS.Keywords: metabolic inflammatory syndrome, adiponectin, atherosclerosis, type 2 diabetes, obesity, inflammation, elderly patients

Aim: Metabolic inflammation syndrome (MIS) can lead to a series of complications, but its exact inflammatory mechanism is still unclear. The aim of this study was to explore the correlation between heparanase (HPA) and MIS, and the close relationship between HPA and other chronic low-grade inflammation index, such as C-reactive protein (CRP) and interleukin-6 (IL-6). Methods: A total of 105 patients with MIS in the physical examination population of Huashan Hospital affiliated to Fudan University from May to June 2018 were selected as the MIS group, and 52 patients who were relatively healthy during the same period were used as the control group. The basic clinical data of the selected candidates were collected, the levels of serum HPA, CRP and IL-6 were measured by ELISA, and the levels of blood glucose and blood lipids were also detected. Results: Compared with the control group, the levels of HPA, CRP, IL-6, FBG, HbA1C, and TG of MIS group were all significantly elevated (all P< 0.05), and HDL-C levels were considerably reduced (P< 0.05). Correlation analysis showed that there was a noticeably positive correlation between serum HPA level and CRP, IL-6 levels (P< 0.05). Conclusion: Higher HPA levels might play a certain role in the occurrence and development of MIS. There was a certain close correlation between serum HPA level and CRP and IL-6 levels, and which indicated that HPA was involved in the chronic low-grade inflammatory reaction process of MIS. [ABSTRACT FROM AUTHOR]

Metabolic inflammation isachronic，low-grade inflammatory stagewhich is elicited by overloading of nutrition and engry. Metabolic inflammatory syndrome (MIS) is a series of metabolic diseases，in which macrophages play an important role, including obesity, non-alcoholic fatty liver disease?type 2 diabetes mellitus^and atherosclerosis. This review explored the role of macrophages in the pathogenesis of MIS and related anti-inflammatory treatment. [ABSTRACT FROM AUTHOR]