Angiotensin II increases adipose angiotensinogen expression

Area of Science:

• Endocrinology and Metabolism
• Cardiovascular Physiology
• Molecular Biology

Background:

• The liver is a primary source of angiotensinogen (AGT).
• Adipose tissue is increasingly recognized as a significant contributor to AGT production.
• The specific roles of angiotensin II (ANG II) receptors in regulating adipose AGT are not fully understood.

Purpose of the Study:

• To identify the angiotensin II (ANG II) receptors involved in regulating angiotensinogen (AGT) in adipose tissue.
• To investigate the relationship between adipose AGT regulation and systemic angiotensin peptide concentrations.

Main Methods:

• Utilized LDL receptor-deficient (LDLR(-/-)) male mice and genetically modified mice lacking angiotensin type 1a (AT(1a)) or angiotensin type 2 (AT(2)) receptors.
• Quantified mRNA abundance of AGT and its receptors (AT(1a)R, AT(2)R) in adipose tissue and liver.
• Administered chronic infusion of ANG II to LDLR(-/-) mice.

Main Results:

• Adipose tissue expresses significant levels of AGT and AT(1a)R mRNA, with higher AT(2)R mRNA than liver.
• AT(1a) receptor deficiency reduced plasma AGT and angiotensin peptides, impacting liver AGT but not adipose AGT.
• AT(2) receptor deficiency increased plasma angiotensin peptides and markedly elevated adipose AGT and AT(1a)R mRNA, an effect abolished by losartan.
• Chronic ANG II infusion robustly increased adipose AGT and AT(1a)R mRNA, with no effect on liver expression.

Conclusions:

• Differential expression of AT(1a) and AT(2) receptors in adipose tissue versus liver mediates tissue-specific ANG II regulation of AGT.
• Adipose tissue plays a crucial role in the activated systemic renin-angiotensin system, particularly under chronic ANG II stimulation.
• Adipose tissue emerges as a key regulator of AGT, influencing systemic angiotensin peptide levels.