The adiponectin signalling pathway - A therapeutic target for the cardiac complications of type 2 diabetes?

Sharma, Abhipree; Mah, Michael; Ritchie, Rebecca H.; Blasio, Miles J. De

doi:10.1016/j.pharmthera.2021.108008

Cited by 28 publications

(23 citation statements)

References 292 publications

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“…AdipoR1 and R2 are downregulated in type 2 diabetes and obesity, causing a decrease in cardiac adiponectin signaling, reducing cardiac protection against cardiac remodeling and lipotoxicity. An adiponectin receptor-mediated signaling pathway is possibly a futuristic approach for diabetic cardiomyopathy [ 56 ]. Inflammatory response syndrome is provoked in cardiopulmonary bypass (CPB) surgery through signaling of both Toll-like receptor 4 (TLR4) and tumor necrosis factor α (TNF-α).…”

Section: Adiponectin and Its Cellular Receptors Adipors “Adiponectin ...mentioning

confidence: 99%

“…Effective treatment is yet to be found; although in T2DM and obesity, adiponectin was reported to be a cardioprotective adipokine that is downregulated, adiponectin signaling is also impaired due to the downregulation of both receptors (AdipoR1 and R2), leading to reducing cardio protection. The protection of adiponectin signaling was found to be against cardiac remodeling and lipo-toxicity [ 56 ]. Adiponectin receptor agonists are small molecules with great therapeutic value; adiponectin mimetic compound ALY688 functioned to stimulate acetyl-CoA carboxylase (ACC) phosphorylation and AMP-activated protein kinase (AMPK) induce glucose oxidation and decrease fat oxidation in adipocytes of both epididymal (Epid) and subcutaneous inguinal (Sc Ing) adipocytes.…”

Section: Adiponectin Plays the Key Link Between Metabolic And Cardiov...mentioning

confidence: 99%

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Adiponectin System (Rescue Hormone): The Missing Link between Metabolic and Cardiovascular Diseases

Aljafary

Al-Suhaimi

2022

Pharmaceutics

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The adipose tissue, regardless of its role in generating and storing energy, acts as a key player as an endocrine tissue, producing a wide scale of cytokines/hormones called adipokines. Adipokines such as leptin, resistin, visfatin and osteopontin own pro-inflammatory effects on the cardiovascular system in some cases. In contrast, some adipokines have cardioprotective and anti-inflammatory impacts including adiponectin, omentin, and apelin. One of the key adipokines is adiponectin, the abundant peptide regulating hormone that is released mainly by adipocytes and cardiomyocytes as well as by endothelial and skeletal cells. It acts through two main receptors: AdipoR1 and AdipoR2, forming the “Adiponectin system” which effectively exerts its cellular mechanisms and responses in target cells. It regulates various metabolic processes, while adiponectin is the adipocyte hormone known for its cardioprotective impact in clinical and experimental research. It is also a well-effector metabolic adipokine, since weight loss or diet restriction show a link with rises in adiponectin concentrations, which is accompanied with increasing insulin sensitivity, glucose, and lipids-regulation via adiponectin’s antioxidant, anti-inflammatory, anti-fibrotic actions. The high adiponectin level made it an attractive player in developing therapeutical treatments for metabolic syndromes and cardiovascular disease. The elevated plasma levels of adiponectin are mostly attributed to its benefits on cardio-metabolism. In some cases, adiponectin has been paradoxically accompanied with elevated risk of cardiovascular disease, so higher adiponectin concentration is a marker of poor prediction. Thus, the adiponectin system is attractive to researchers as a biomarker of heart disease advancement and a predictor of prognosis during the term of some cardiovascular diseases and its mechanical functions in Hypertension and diabetic patients. This review highlights the physiological roles of adiponectin as an anti-inflammatory and cardioprotective hormone as well as how it plays as a biomarker and potential therapeutic tool in the cardiovascular system in adult, children, and adolescents. The adiponectin system may be seen as a rescue hormone aiding in remodeling of the cardiovascular system on both cellular and molecular levels. The paradox role of adiponectin relevant to cardiovascular mortality should be taken into consideration.

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Section: Adiponectin and Its Cellular Receptors Adipors “Adiponectin ...mentioning

confidence: 99%

Section: Adiponectin Plays the Key Link Between Metabolic And Cardiov...mentioning

confidence: 99%

Adiponectin System (Rescue Hormone): The Missing Link between Metabolic and Cardiovascular Diseases

Aljafary

Al-Suhaimi

2022

Pharmaceutics

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“…Myocardial hypertrophy is the next hallmark of DCM, resulting from the cell-death-mediated loss of cardiomyocytes and subsequent compensative enlargement of the remaining viable cardiomyocytes. On the cellular level, hypertrophy is described with disorganised cardiomyocyte myofiber; on the molecular level, with the over-expression of the key regulatory genes: β-MHC (β-myosin heavy chain), FoxO1 (forkhead box protein O 1), BNP (brain natriuretic peptide), ANP (atrial natriuretic peptide), adiponectin signalling pathway, and others [ 24 , 25 ]. Despite extensive and meticulous research, the exact molecular mechanism of cardiac hypertrophy pathogenesis is not fully understood.…”

Section: Structural and Functional Alterations In Dcmmentioning

confidence: 99%

The Role of Mitochondrial Abnormalities in Diabetic Cardiomyopathy

Dabravolski

Sadykhov

Kartuesov

et al. 2022

IJMS

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Diabetic cardiomyopathy (DCM) is defined as the presence in diabetic patients of abnormal cardiac structure and performance (such as left ventricular hypertrophy, fibrosis, and arrhythmia) in the absence of other cardiac risk factors (such as hypertension or coronary artery disease). Although the pathogenesis of DCM remains unclear currently, mitochondrial structural and functional dysfunctions are recognised as a central player in the DCM development. In this review, we focus on the role of mitochondrial dynamics, biogenesis and mitophagy, Ca2+ metabolism and bioenergetics in the DCM development and progression. Based on the crucial role of mitochondria in DCM, application of mitochondria-targeting therapies could be effective strategies to slow down the progression of the disease.

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“…APN was first identified in 1995 ( 167 ) and was known to be specifically expressed in adipose tissue and fully differentiated adipocytes ( 168 ). While adipokines like omentin and chemerin are also cardioprotective, APN is the most abundant adipokines in adipose tissue, and possesses insulin-sensitizing effects ( 169 ).…”

Section: Adiponectin and Its Potential As A Treatment Target For Diab...mentioning

confidence: 99%

“…Both human and murine cardiomyocyte-derived APN has been demonstrated to be biologically active, protecting cardiomyocytes from simulated ischemia/reperfusion injury and directly impacting cardiac metabolism by activating APN receptors via an autocrine/paracrine mechanism ( 177 , 178 ). The epicardial and pericardial adipose tissue were also found to secret proinflammatory adipocytokines that may exert local paracrine effects on the heart ( 168 ). A subsequent study from Achari and Jain ( 179 ) found that HMW and globular adiponectin (a proteolytic cleavage product of full length APN) are the most biologically active forms of APN thought to be primarily responsible for mediating its cardioprotective effects.…”

Section: Adiponectin and Its Potential As A Treatment Target For Diab...mentioning

confidence: 99%

The importance of caveolin as a target in the prevention and treatment of diabetic cardiomyopathy

Xia

Li²,

Wu³

et al. 2022

Front. Immunol.

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The diabetic population has been increasing in the past decades and diabetic cardiomyopathy (DCM), a pathology that is defined by the presence of cardiac remodeling and dysfunction without conventional cardiac risk factors such as hypertension and coronary heart diseases, would eventually lead to fatal heart failure in the absence of effective treatment. Impaired insulin signaling, commonly known as insulin resistance, plays an important role in the development of DCM. A family of integral membrane proteins named caveolins (mainly caveolin-1 and caveolin-3 in the myocardium) and a protein hormone adiponectin (APN) have all been shown to be important for maintaining normal insulin signaling. Abnormalities in caveolins and APN have respectively been demonstrated to cause DCM. This review aims to summarize recent research findings of the roles and mechanisms of caveolins and APN in the development of DCM, and also explore the possible interplay between caveolins and APN.

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The adiponectin signalling pathway - A therapeutic target for the cardiac complications of type 2 diabetes?

Cited by 28 publications

References 292 publications

Adiponectin System (Rescue Hormone): The Missing Link between Metabolic and Cardiovascular Diseases

Adiponectin System (Rescue Hormone): The Missing Link between Metabolic and Cardiovascular Diseases

The Role of Mitochondrial Abnormalities in Diabetic Cardiomyopathy

The importance of caveolin as a target in the prevention and treatment of diabetic cardiomyopathy

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