TY - JOUR
T1 - Neutral sphingomyelinase-2 and cardiometabolic diseases
AU - Sindhu, Sardar
AU - Leung, Yat Hei
AU - Arefanian, Hossein
AU - Madiraju, S. R.Murthy
AU - Al-Mulla, Fahd
AU - Ahmad, Rasheed
AU - Prentki, Marc
N1 - Funding Information:
This study was supported by funds from Montreal Medical International/Dasman Diabetes Institute (to M.P., S.R.M.M., and R.A.) and the Canadian Institutes of Health Research (to M.P. and S.R.M.M.).
Publisher Copyright:
© 2021 The Authors. Obesity Reviews published by John Wiley & Sons Ltd on behalf of World Obesity Federation.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021
Y1 - 2021
N2 - Sphingolipids, in particular ceramides, play vital role in pathophysiological processes linked to metabolic syndrome, with implications in the development of insulin resistance, pancreatic ß-cell dysfunction, type 2 diabetes, atherosclerosis, inflammation, nonalcoholic steatohepatitis, and cancer. Ceramides are produced by the hydrolysis of sphingomyelin, catalyzed by different sphingomyelinases, including neutral sphingomyelinase 2 (nSMase2), whose dysregulation appears to underlie many of the inflammation-related pathologies. In this review, we discuss the current knowledge on the biochemistry of nSMase2 and ceramide production and its regulation by inflammatory cytokines, with particular reference to cardiometabolic diseases. nSMase2 contribution to pathogenic processes appears to involve cyclical feed-forward interaction with proinflammatory cytokines, such as TNF-α and IL-1ß, which activate nSMase2 and the production of ceramides, that in turn triggers the synthesis and release of inflammatory cytokines. We elaborate these pathogenic interactions at the molecular level and discuss the potential therapeutic benefits of inhibiting nSMase2 against inflammation-driven cardiometabolic diseases.
AB - Sphingolipids, in particular ceramides, play vital role in pathophysiological processes linked to metabolic syndrome, with implications in the development of insulin resistance, pancreatic ß-cell dysfunction, type 2 diabetes, atherosclerosis, inflammation, nonalcoholic steatohepatitis, and cancer. Ceramides are produced by the hydrolysis of sphingomyelin, catalyzed by different sphingomyelinases, including neutral sphingomyelinase 2 (nSMase2), whose dysregulation appears to underlie many of the inflammation-related pathologies. In this review, we discuss the current knowledge on the biochemistry of nSMase2 and ceramide production and its regulation by inflammatory cytokines, with particular reference to cardiometabolic diseases. nSMase2 contribution to pathogenic processes appears to involve cyclical feed-forward interaction with proinflammatory cytokines, such as TNF-α and IL-1ß, which activate nSMase2 and the production of ceramides, that in turn triggers the synthesis and release of inflammatory cytokines. We elaborate these pathogenic interactions at the molecular level and discuss the potential therapeutic benefits of inhibiting nSMase2 against inflammation-driven cardiometabolic diseases.
KW - cardiometabolic diseases
KW - ceramide
KW - nSMase2
KW - sphingolipid
UR - http://www.scopus.com/inward/record.url?scp=85102704637&partnerID=8YFLogxK
U2 - 10.1111/obr.13248
DO - 10.1111/obr.13248
M3 - Article
AN - SCOPUS:85102704637
JO - Obesity Reviews
JF - Obesity Reviews
SN - 1467-7881
ER -