TY - JOUR
T1 - Inhibition of the Renin-Angiotensin System Reduces Gene Expression of Inflammatory Mediators in Adipose Tissue Independent of Energy Balance
AU - Mitchell, Caitlin S.
AU - Premaratna, Shirmila D.
AU - Bennett, Garth
AU - Lambrou, Maria
AU - Stahl, Lauren A.
AU - Jois, Markandeya
AU - Barber, Elizabeth
AU - Antoniadis, Christopher P.
AU - Woods, Stephen C.
AU - Cameron-Smith, David
AU - Weisinger, Richard S.
AU - Begg, Denovan P.
N1 - Funding Information:
This work was supported by the Australian Research Council (DE160100088 and DP170100063), the National Health and Medical Research Council APP1156622, and a Ramaciotti Foundation Establishment Grant.
Publisher Copyright:
© Copyright © 2021 Mitchell, Premaratna, Bennett, Lambrou, Stahl, Jois, Barber, Antoniadis, Woods, Cameron-Smith, Weisinger and Begg.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/6/2
Y1 - 2021/6/2
N2 - Obesity is a growing health problem worldwide. The renin-angiotensin system (RAS) is present in adipose tissue, and evidence suggests that it is involved in both diet-induced obesity and the inflammation associated with obesity. The present experiments determined the effect of (1) different angiotensin-converting enzyme (ACE) inhibitors (captopril, perindopril, enalapril) and angiotensin receptor blockers (ARBs: telmisartan, losartan) on adiposity of mice fed a high-fat diet for 28 days (2); acute treatment with the ACE-inhibitor captopril on gene expression of inflammatory markers in mice fed a high-fat diet (HFD); and (3) short-term (2 days) and chronic (28 days) treatment of ACE-inhibition on energy expenditure (EE) and energy balance in mice fed HFD ad libitum (AL), as well as receiving HFD limited to the amount of calories eaten by controls (pair-fed (PF) group). Body weight, food intake, adiposity and plasma leptin were lower in ACE inhibitor or ARB-treated groups over 28 days compared with HFD untreated mice. Short-term treatment with captopril led to increased EE relative to the level in the PF group. After 28 days, EE was lower in both captopril-treated and PF mice compared with AL, but the effect was greater in the captopril-treated group. Adiponectin was elevated in captopril-treated mice, but not in PF mice, after both 2 and 28 days. Additionally, acute RAS blockade in HFD-fed mice reduced mRNA expression for MCP-1, IL-6, TLR4, and leptin in adipose tissue relative to values in untreated groups. These data demonstrate that ACE inhibition and angiotensin receptor blockade reduce food intake to produce weight loss and suggest that the anti-inflammatory effects of ACE inhibition may be independent of weight loss.
AB - Obesity is a growing health problem worldwide. The renin-angiotensin system (RAS) is present in adipose tissue, and evidence suggests that it is involved in both diet-induced obesity and the inflammation associated with obesity. The present experiments determined the effect of (1) different angiotensin-converting enzyme (ACE) inhibitors (captopril, perindopril, enalapril) and angiotensin receptor blockers (ARBs: telmisartan, losartan) on adiposity of mice fed a high-fat diet for 28 days (2); acute treatment with the ACE-inhibitor captopril on gene expression of inflammatory markers in mice fed a high-fat diet (HFD); and (3) short-term (2 days) and chronic (28 days) treatment of ACE-inhibition on energy expenditure (EE) and energy balance in mice fed HFD ad libitum (AL), as well as receiving HFD limited to the amount of calories eaten by controls (pair-fed (PF) group). Body weight, food intake, adiposity and plasma leptin were lower in ACE inhibitor or ARB-treated groups over 28 days compared with HFD untreated mice. Short-term treatment with captopril led to increased EE relative to the level in the PF group. After 28 days, EE was lower in both captopril-treated and PF mice compared with AL, but the effect was greater in the captopril-treated group. Adiponectin was elevated in captopril-treated mice, but not in PF mice, after both 2 and 28 days. Additionally, acute RAS blockade in HFD-fed mice reduced mRNA expression for MCP-1, IL-6, TLR4, and leptin in adipose tissue relative to values in untreated groups. These data demonstrate that ACE inhibition and angiotensin receptor blockade reduce food intake to produce weight loss and suggest that the anti-inflammatory effects of ACE inhibition may be independent of weight loss.
KW - adipose tissue
KW - body weight
KW - energy expenditure
KW - gene expression
KW - inflammatory mediators
KW - obesity
KW - renin-angiotensin system antagonists
UR - http://www.scopus.com/inward/record.url?scp=85108056266&partnerID=8YFLogxK
U2 - 10.3389/fendo.2021.682726
DO - 10.3389/fendo.2021.682726
M3 - Article
C2 - 34149621
AN - SCOPUS:85108056266
SN - 1664-2392
VL - 12
JO - Frontiers in Endocrinology
JF - Frontiers in Endocrinology
M1 - 682726
ER -