ACE2 is expressed in mouse adipocytes and regulated by a high-fat diet
Autor: | Manisha Gupte, Carine M. Boustany-Kari, Kalyani Bharadwaj, Sara Police, Sean Thatcher, Ming C. Gong, Victoria L. English, Lisa A. Cassis |
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Rok vydání: | 2008 |
Předmět: |
Male
medicine.medical_specialty Angiotensins Physiology Prohormone Adipose tissue Blood Pressure Biology ADAM17 Protein Peptidyl-Dipeptidase A Appetite Obesity and Digestion Gene Expression Regulation Enzymologic chemistry.chemical_compound Mice Adipocyte Internal medicine 3T3-L1 Cells Physiology (medical) Renin–angiotensin system medicine Adipocytes Animals RNA Messenger Angiotensin-converting enzyme Angiotensin II Dietary Fats Enzyme Activation Mice Inbred C57BL PPAR gamma ADAM Proteins Endocrinology chemistry Adipose Tissue Angiotensin-converting enzyme 2 biology.protein Angiotensin-Converting Enzyme 2 medicine.symptom Vasoconstriction hormones hormone substitutes and hormone antagonists medicine.drug |
Zdroj: | American Journal of Physiology-Regulatory, Integrative and Comparative Physiology |
ISSN: | 1522-1490 0363-6119 |
DOI: | 10.1152/ajpregu.00183.2008 |
Popis: | 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. |
Databáze: | OpenAIRE |
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