ACE2 is expressed in mouse adipocytes and regulated by a high-fat diet.
Adipose tissue expresses components of the renin-angiotensin system (RAS). Angiotensin converting enzyme (ACE2), a new component of the RAS, catabolizes the vasoconstrictor peptide ANG II to form the vasodilator angiotensin 1-7 [ANG-(1-7)]. We examined whether adipocytes express ACE2 and its regulation by manipulation of the RAS and by high-fat (HF) feeding. ACE2 mRNA expression increased (threefold) during differentiation of 3T3-L1 adipocytes and was not regulated by manipulation of the RAS. Male C57BL/6 mice were fed low- (LF) or high-fat (HF) diets for 1 wk or 4 mo. At 1 wk of HF feeding, adipose expression of angiotensinogen (twofold) and ACE2 (threefold) increased, but systemic angiotensin peptide concentrations and blood pressure were not altered. At 4 mo of HF feeding, adipose mRNA expression of angiotensinogen (twofold) and ACE2 (threefold) continued to be elevated, and liver angiotensinogen expression increased (twofold). However, adipose tissue from HF mice did not exhibit elevated ACE2 protein or activity. Increased expression of ADAM17, a protease responsible for ACE2 shedding, coincided with reductions in ACE2 activity in 3T3-L1 adipocytes, and an ADAM17 inhibitor decreased media ACE2 activity. Moreover, ADAM17 mRNA expression was increased in adipose tissue from 4-mo HF-fed mice, and plasma ACE2 activity increased. However, HF mice exhibited marked increases in plasma angiotensin peptide concentrations (LF: 2,141 +/- 253; HF: 6,829 +/- 1,075 pg/ml) and elevated blood pressure. These results demonstrate that adipocytes express ACE2 that is dysregulated in HF-fed mice with elevated blood pressure compared with LF controls.
Gupte
Manisha
M
Graduate Center for Nutritional Sciences, Rm. 521b, Wethington Bldg., 900 S. Limestone, College of Medicine, Univ. of Kentucky, Lexington, KY 40536-0200, USA.
Boustany-Kari
Carine M
CM
Bharadwaj
Kalyani
K
Police
Sara
S
Thatcher
Sean
S
Gong
Ming C
MC
English
Victoria L
VL
Cassis
Lisa A
LA
D041721:3T3-L1 Cells; D051722:ADAM Proteins / Q000235:genetics; D000072198:ADAM17 Protein; D017667:Adipocytes / Q000166:cytology / Q000201:enzymology*; D000273:Adipose Tissue / Q000166:cytology / Q000201:enzymology; D000085962:Angiotensin-Converting Enzyme 2; D000809:Angiotensins / Q000097:blood; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D004041:Dietary Fats / Q000494:pharmacology*; D004789:Enzyme Activation / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D047495:PPAR gamma / Q000235:genetics; D007703:Peptidyl-Dipeptidase A / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism
D000809:Angiotensins; D004041:Dietary Fats; D047495:PPAR gamma; D012333:RNA, Messenger; D007703:Peptidyl-Dipeptidase A; C000705328:Ace2 protein, mouse; D000085962:Angiotensin-Converting Enzyme 2; D051722:ADAM Proteins; D000072198:ADAM17 Protein; C000606463:Adam17 protein, mouse