Abstract

A healthy adipose tissue (AT) is indispensable to human wellbeing. Among other roles, it contributes to energy homeostasis and provides insulation for internal organs. Adipocytes were previously thought to be a passive store of excess calories, however this view evolved to include an endocrine role. Adipose tissue was shown to synthesize and secrete adipokines that are pertinent to glucose and lipid homeostasis, as well as inflammation. Importantly, the obesity-induced adipose tissue expansion stimulates a plethora of signals capable of triggering an inflammatory response. These inflammatory manifestations of obese AT have been linked to insulin resistance, metabolic syndrome, and type 2 diabetes, and proposed to evoke obesity-induced comorbidities including cardiovascular diseases (CVDs). A growing body of evidence suggests that metabolic disorders, characterized by AT inflammation and accumulation around organs may eventually induce organ dysfunction through a direct local mechanism. Interestingly, perirenal adipose tissue (PRAT), surrounding the kidney, influences renal function and metabolism. In this regard, PRAT emerged as an independent risk factor for chronic kidney disease (CKD) and is even correlated with CVD. Here, we review the available evidence on the impact of PRAT alteration in different metabolic states on the renal and cardiovascular function. We present a broad overview of novel insights linking cardiovascular derangements and CKD with a focus on metabolic disorders affecting PRAT. We also argue that the confluence among these pathways may open several perspectives for future pharmacological therapies against CKD and CVD possibly by modulating PRAT immunometabolism.

Highlights

  • Adipose tissue (AT) is an active cellular complex that includes three different cellular types: white, brown, and beige adipocytes where extensive molecular, physiological and metabolic heterogeneity among different adipose depots exists [1,2,3]

  • While unilocular UCP1-expressing adipocytes are evenly distributed within perirenal adipose tissue (PRAT), multilocular UCP1-expressing adipocytes are located around the adrenal gland, in areas containing a higher number of sympathetic nerve endings [21]

  • The functional significance of PRAT production of renin-angiotensin system (RAS) components is an area of intense investigation, it could reveal a link between metabolic dysfunction, cardiovascular diseases (CVDs), and chronic kidney disease (CKD)

Read more

Summary

INTRODUCTION

Adipose tissue (AT) is an active cellular complex that includes three different cellular types: white, brown, and beige adipocytes where extensive molecular, physiological and metabolic heterogeneity among different adipose depots exists [1,2,3]. While unilocular UCP1-expressing adipocytes are evenly distributed within PRAT, multilocular UCP1-expressing adipocytes are located around the adrenal gland, in areas containing a higher number of sympathetic nerve endings [21] These two types of AT are associated with preadipocytes, mesenchymal stem cells, and several inflammatory cells [12]. Stronger browning capacity in females is associated with specific characteristics of mesenchymal cells of PRAT and to a much lesser extent related to hormonal interventions [30] These findings are confirmed by a study on a murine model showing that Y-chromosome suppresses BAT UCP-1 expression [31]. PRAT manifests an immunoregulatory phenotype in response to several inflammatory cytokines as interleukin-1 beta (IL-1b), interferon (IFN), and tumor necrosis factor alpha (TNF-a) which could be targeted in antiinflammatory therapy [27] These cytokines produced can regulate kidney function through paracrine or endocrine pathways. This represents a potential immunomodulatory mechanism that could be targeted in different aspects of inflammatory conditions, tissue injuries [27], CVD and renal dysfunction

Sympathetic Innervation
Mechanisms Governing Adipose Tissue Inflammation and Thermogenesis
Mechanisms Linking Perirenal Adipose Tissue Thermogenesis and Inflammation
PERIRENAL ADIPOSE TISSUE AND RENAL DISEASES
Possible Mechanisms
Conducted on Reference
Rats with metabolic syndrome Obese mouse model
PERIRENAL ADIPOSE TISSUE AND CARDIOVASCULAR DYSFUNCTION
Targeted population and references
FUTURE PERSPECTIVE AND POSSIBLE TREATMENT
CONCLUSION
Findings
AUTHOR CONTRIBUTIONS
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call