Emerging roles of cardiolipin remodeling in mitochondrial dysfunction associated with diabetes,obesity,and cardiovascular diseases

Cardiolipin （CL） is a phospholipid exclusively localized in inner mitochondrial membrane where it is required for oxidative phosphorylation, ATP synthesis, and mitochondrial bioenergetics. The biological functions of CL are thought to depend on its acyl chain composition which is dominated by linoleic acids in metabolically active tissues. This unique feature is not derived from the de novo biosynthesis of CL, rather from a remodeling process that involves in phospholipases and transacylase/acyltransferase. The remodeling process is also believed to be responsible for generation of CL species that causes oxidative stress and mitochondrial dysfunction. CL is highly sensitive to oxidative damages by reactive oxygen species （ROS） due to its high content in polyunsaturated fatty acids and location near the site of ROS production. Consequently, pathological remodeling of CL has been implicated in the etiology of mitochondrial dysfunction commonly associated with diabetes, obesity, heart failure, neurodegeneration, and aging that are characterized by oxidative stress, CL deficiency, and abnormal CL species. This review summarizes recent progresses in molecular, enzymatic, lipidomic, and metabolic studies that support a critical regulatory role of pathological CL remodeling as a missing link between oxidative stress and mitochondrial dysfunction in metabolic diseases and aging.

Obesity and the risk of cardiovascular disease and diabetes mellitus

The increasing prevalence of obesity worldwide has many experts concerned about the worsening health of a large proportion of the population. It is well recognized that obesity is associated with a higher mortality, an increased risk of hypertension and hyperlipidemia, cardiovascular disease, diabetes mellitus, osteoarthritis, gall bladder disease and possibly some cancers. Currently it is estimated that over two thirds of adults in the United States are overweight and nearly one third are clinically obese.1 Of special concern is the rapid increase in obesity among children. Other countries both developed and developing are experiencing similar trends.……

Role of cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon genes pathway in diabetes and its complications

Diabetes mellitus(DM)is one of the major causes of mortality worldwide,with inflammation being an important factor in its onset and development.This review summarizes the specific mechanisms of the cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)-stimulator of interferon genes(STING)pathway in mediating inflammatory responses.Furthermore,it compre-hensively presents related research progress and the subsequent involvement of this pathway in the pathogenesis of early-stage DM,diabetic gastroenteropathy,diabetic cardiomyopathy,non-alcoholic fatty liver disease,and other complic-ations.Additionally,the role of cGAS-STING in autonomic dysfunction and intes-tinal dysregulation,which can lead to digestive complications,has been discuss-ed.Altogether,this study provides a comprehensive analysis of the research advances regarding the cGAS-STING pathway-targeted therapeutic agents and the prospects for their application in the precision treatment of DM.

New perspectives on angiotensin-converting enzyme 2 and its related diseases

Since the worldwide outbreak of coronavirus disease 2019,angiotensin-converting enzyme 2(ACE2)has received widespread attention as the cell receptor of the severe acute respiratory syndrome coronavirus 2 virus.At the same time,as a key enzyme in the renin-angiotensin-system,ACE2 is considered to be an endogenous negative regulator of vasoconstriction,proliferation,fibrosis,and proinflammation caused by the ACE-angiotensin II-angiotensin type 1 receptor axis.ACE2 is now implicated as being closely connected to diabetes,cardiovascular,kidney,and lung diseases,and so on.This review covers the available information on the host factors regulating ACE2 and discusses its role in a variety of pathophysiological conditions in animal models and humans.

IKK inhibition prevents PM_(2.5)-exacerbated cardiac injury in mice with type 2 diabetes

Epidemiological studies have found that individuals with diabetes mellitus（DM） display an increased susceptibility for adverse cardiovascular outcomes when exposed to air pollution.This study was conducted to explore the potential mechanism linking ambient fine particles（PM2.5） and heart injury in a Type 2 DM（T2DM） animal model. The KKay mouse, an animal model of T2DM, was exposed to concentrated ambient PM2.5 or filtered air for 8 weeks via a versatile aerosol exposure and concentrator system. Simultaneously, an inhibitor of IκB kinase-2（IKK-a）（IMD-0354）, which is a blocker of nuclear factor κB（NF-κB）nuclear translocation, was administrated by intracerebroventricular injection（ICV） to regulate the NF-êB pathway. The results showed that ambient PM2.5 induced the increase of, NF-êB, cyclooxygenase-2（COX-2） and mitogen activated protein kinase（MAPK） expression in cardiac tissue, and that IMD-0354 could alleviate the inflammatory injury. The results suggested that the NF-êB pathway plays an important role in mediating the PM2.5-induced cardiovascular injury in the T2DM model. Inhibiting NFκB may be a therapeutic option in air-pollution-exacerbated cardiovascular injury in diabetes mellitus.