The obesity epidemic continues to challenge global cardiovascular(CV)health,but not all obesity is equal.Emerging evidence underscores that distinct obesity phenotypes—particularly metabolically healthy vs unhealthy ...The obesity epidemic continues to challenge global cardiovascular(CV)health,but not all obesity is equal.Emerging evidence underscores that distinct obesity phenotypes—particularly metabolically healthy vs unhealthy profiles—confer differential CV risks.Recent large-scale studies have revealed that even metabol-ically healthy obesity(MHO)is associated with an increased risk of adverse CV events,particularly in the context of socioeconomic disadvantage.Central is the role of chronic low-grade inflammation,termed“metaflammation”,which can persist even in the absence of overt metabolic syndrome and is shaped by both gender and fat distribution.Epicardial and visceral adiposity contribute to this pro-inflammatory state and are strongly associated with conditions such as heart failure and atrial fibrillation.Notably,aging and hormonal changes,particularly in women,may destabilize MHO status,increasing CV vulnerability over time.This overview calls for a paradigm shift in cardiometabolic care,moving beyond anthropometric parameters toward a more refined assessment that incorporate inflammatory biomarkers,fat distribution and sex-specific factors.Recognizing these underlying biological and phenotypic differences enables more accurate CV risk stratification and supports the development of precision-based therapeutic strategies.Ultimately,understanding not just who is at risk,but why,is essential to improving prevention and outcomes across diverse populations facing the bur-den of obesity.展开更多
Metaflammation is responsible for several metabolic syndromes,such as type 2 diabetes.However,the mechanisms by which metabolic disorders trigger metaflammation remain unclear.We identified a cell type-specific downre...Metaflammation is responsible for several metabolic syndromes,such as type 2 diabetes.However,the mechanisms by which metabolic disorders trigger metaflammation remain unclear.We identified a cell type-specific downregulation of CD1d expression in M2 macrophages during the progression of obesity prior to the onset of inflammation in visceral adipose tissues.A reduction in CD1d expression influenced the ability of M2 macrophages to present antigens and caused a change in antigen-presenting cells from M2 macrophages to M1 macrophages.With CD1d conditional knockout(KO)mice,we further demonstrated that natural killer T(NKT)cell activation by M2 macrophages inhibited metaflammation and insulin resistance by promoting Th2 responses and M2 polarization in visceral adipose tissues of obese mice,whereas NKT cell activation by M1 macrophages exacerbated metaflammation and insulin resistance by promoting Th1 responses and inhibiting M2 polarization.Our results suggest that an M2-specific reduction of CD1d is an initiating event that switches NKT cell-mediated immune responses and disrupts the immune balance in visceral adipose tissues in obese mice.展开更多
Prediabetes is an important stage in the development of diabetes.It is necessary to find a safe,effective and sustainable way to delay and reverse the progression of prediabetes.Akkermansia muciniphila(A.muciniphila)i...Prediabetes is an important stage in the development of diabetes.It is necessary to find a safe,effective and sustainable way to delay and reverse the progression of prediabetes.Akkermansia muciniphila(A.muciniphila)is one of the key bacteria associated with glucose metabolism.Recent studies mainly focus on the effect of A.muciniphila on obesity and insulin resistance,but there is no research on the effect of A.muciniphila on pancreaticβ-cell function and its mechanism in prediabetes.In this study,we investigated the effects of A.muciniphila onβ-cell function,apoptosis and differentiation,as well as its effects on the gut microbiome,intestinal barrier,metaflammation and the expression of Toll-like receptors(TLRs)in a high-fat diet(HFD)-induced prediabetic rat model.The effect of A.muciniphila was compared with dietary intervention.The results showed both A.muciniphila treatment and dietary intervention can reduce metaflammation by repairing the intestinal barrier in rats with prediabetes induced by an HFD and improveβ-cell secretory function,apoptosis and differentiation through signaling pathways mediated by TLR2 and TLR4.Additionally,A.muciniphila can further elevateβ-cell secretion,attenuate apoptosis and improve differentiation and the TLR signaling pathway on the basis of diet.展开更多
Worldwide stroke is increasing in parallel with modernization,changes in lifestyle,and the growing elderly population.Our review is focused on the link between diet,as part of‘modern lifestyle’,and health in the con...Worldwide stroke is increasing in parallel with modernization,changes in lifestyle,and the growing elderly population.Our review is focused on the link between diet,as part of‘modern lifestyle’,and health in the context of genetic predisposition of individuals to‘unhealthy’metabolic pathway activity.It is concluded that lifestyle including high sugar diets,alcohol and tobacco addiction or high fat diets as well as ageing,brain injury,oxidative stress and neuroinflammation,negatively influence the onset,severity and duration of neurodegenerative diseases.Fortunately,there are several healthy dietary components such as polyunsaturated fatty acids and the anti-oxidants curcumin,resveratrol,blueberry polyphenols,sulphoraphane,salvionic acid as well as caloric restriction and physical activity,which may counteract ageing and associated neurodegenerative diseases via increased autophagy or increased neurogenesis in the adult brain.展开更多
Emerging lines of evidence have shown that the production of the covalently closed single-stranded circular RNAs is not splicing errors,but rather a regulated process with distinct biogenesis and turnover.Circular RNA...Emerging lines of evidence have shown that the production of the covalently closed single-stranded circular RNAs is not splicing errors,but rather a regulated process with distinct biogenesis and turnover.Circular RNAs are expressed in a cell type-and tissue-specific manner and often localize to specific subcellular regions or organelles for functions.The dysregulation of circular RNAs from birth to death is linked to the pathogenesis and progression of diverse diseases.This review outlines how aberrant circular RNA biogenesis,subcellular location,and degradation are linked to disease progression,focusing on metaflammation and cancers.We also discuss potential therapeutic strategies and obstacles in targeting such disease-related circular RNAs.展开更多
文摘The obesity epidemic continues to challenge global cardiovascular(CV)health,but not all obesity is equal.Emerging evidence underscores that distinct obesity phenotypes—particularly metabolically healthy vs unhealthy profiles—confer differential CV risks.Recent large-scale studies have revealed that even metabol-ically healthy obesity(MHO)is associated with an increased risk of adverse CV events,particularly in the context of socioeconomic disadvantage.Central is the role of chronic low-grade inflammation,termed“metaflammation”,which can persist even in the absence of overt metabolic syndrome and is shaped by both gender and fat distribution.Epicardial and visceral adiposity contribute to this pro-inflammatory state and are strongly associated with conditions such as heart failure and atrial fibrillation.Notably,aging and hormonal changes,particularly in women,may destabilize MHO status,increasing CV vulnerability over time.This overview calls for a paradigm shift in cardiometabolic care,moving beyond anthropometric parameters toward a more refined assessment that incorporate inflammatory biomarkers,fat distribution and sex-specific factors.Recognizing these underlying biological and phenotypic differences enables more accurate CV risk stratification and supports the development of precision-based therapeutic strategies.Ultimately,understanding not just who is at risk,but why,is essential to improving prevention and outcomes across diverse populations facing the bur-den of obesity.
基金supported by the Major State Basic Research Development Program of China(973 Program)2013CB944902the National Natural Science Foundation of China 91542203 and 31470859+1 种基金the Strategic Priority Research Program of the Chinese Academy of Sciences XDA12030201the Fundamental Research Funds for the Central Universities and Users with Potential 2015HSC-UP018.
文摘Metaflammation is responsible for several metabolic syndromes,such as type 2 diabetes.However,the mechanisms by which metabolic disorders trigger metaflammation remain unclear.We identified a cell type-specific downregulation of CD1d expression in M2 macrophages during the progression of obesity prior to the onset of inflammation in visceral adipose tissues.A reduction in CD1d expression influenced the ability of M2 macrophages to present antigens and caused a change in antigen-presenting cells from M2 macrophages to M1 macrophages.With CD1d conditional knockout(KO)mice,we further demonstrated that natural killer T(NKT)cell activation by M2 macrophages inhibited metaflammation and insulin resistance by promoting Th2 responses and M2 polarization in visceral adipose tissues of obese mice,whereas NKT cell activation by M1 macrophages exacerbated metaflammation and insulin resistance by promoting Th1 responses and inhibiting M2 polarization.Our results suggest that an M2-specific reduction of CD1d is an initiating event that switches NKT cell-mediated immune responses and disrupts the immune balance in visceral adipose tissues in obese mice.
基金financially supported by the National Natural Science Foundation of China(81870596,81870594)the Clinical research plan of Shanghai Hospital Development Center[No.SHDC2020CR1016B].
文摘Prediabetes is an important stage in the development of diabetes.It is necessary to find a safe,effective and sustainable way to delay and reverse the progression of prediabetes.Akkermansia muciniphila(A.muciniphila)is one of the key bacteria associated with glucose metabolism.Recent studies mainly focus on the effect of A.muciniphila on obesity and insulin resistance,but there is no research on the effect of A.muciniphila on pancreaticβ-cell function and its mechanism in prediabetes.In this study,we investigated the effects of A.muciniphila onβ-cell function,apoptosis and differentiation,as well as its effects on the gut microbiome,intestinal barrier,metaflammation and the expression of Toll-like receptors(TLRs)in a high-fat diet(HFD)-induced prediabetic rat model.The effect of A.muciniphila was compared with dietary intervention.The results showed both A.muciniphila treatment and dietary intervention can reduce metaflammation by repairing the intestinal barrier in rats with prediabetes induced by an HFD and improveβ-cell secretory function,apoptosis and differentiation through signaling pathways mediated by TLR2 and TLR4.Additionally,A.muciniphila can further elevateβ-cell secretion,attenuate apoptosis and improve differentiation and the TLR signaling pathway on the basis of diet.
文摘Worldwide stroke is increasing in parallel with modernization,changes in lifestyle,and the growing elderly population.Our review is focused on the link between diet,as part of‘modern lifestyle’,and health in the context of genetic predisposition of individuals to‘unhealthy’metabolic pathway activity.It is concluded that lifestyle including high sugar diets,alcohol and tobacco addiction or high fat diets as well as ageing,brain injury,oxidative stress and neuroinflammation,negatively influence the onset,severity and duration of neurodegenerative diseases.Fortunately,there are several healthy dietary components such as polyunsaturated fatty acids and the anti-oxidants curcumin,resveratrol,blueberry polyphenols,sulphoraphane,salvionic acid as well as caloric restriction and physical activity,which may counteract ageing and associated neurodegenerative diseases via increased autophagy or increased neurogenesis in the adult brain.
基金the National Key Research and Development Program of China(2021YFA1300502)the Natural Science Foundation of China(92057210,82125017,91942309)the Science and Technology Program of Guangzhou(202103000070)。
文摘Emerging lines of evidence have shown that the production of the covalently closed single-stranded circular RNAs is not splicing errors,but rather a regulated process with distinct biogenesis and turnover.Circular RNAs are expressed in a cell type-and tissue-specific manner and often localize to specific subcellular regions or organelles for functions.The dysregulation of circular RNAs from birth to death is linked to the pathogenesis and progression of diverse diseases.This review outlines how aberrant circular RNA biogenesis,subcellular location,and degradation are linked to disease progression,focusing on metaflammation and cancers.We also discuss potential therapeutic strategies and obstacles in targeting such disease-related circular RNAs.
