ACE2 pathway regulates thermogenesis and energy metabolism

Area of Science:

• Metabolic research
• Endocrinology
• Physiology

Background:

• Energy homeostasis is vital for metabolic health, with obesity and diabetes posing significant challenges.
• The Angiotensin-Converting Enzyme 2 (ACE2) pathway, involving Angiotensin II (Ang II) and the Mas1 receptor, plays a role in cardiovascular function.
• Understanding regulators of thermogenesis is key to developing treatments for metabolic disorders.

Purpose of the Study:

• To investigate the role of the ACE2 pathway in thermogenesis and energy expenditure.
• To explore the therapeutic potential of modulating the ACE2 pathway for metabolic disorders.

Main Methods:

• Analysis of ACE2 and Ang-(1-7) levels in brown adipose tissue (BAT) and serum under cold stimulation.
• Utilizing knockout mouse models (Ace2, Mas1) and tissue transplantation.
• Employing overexpression of Ace2 and Ang-(1-7) infusion in diet-induced and genetic obesity models.
• Investigating downstream signaling pathways including Akt/FoxO1 and PKA.

Main Results:

• ACE2 is highly expressed in BAT, and its levels increase with cold exposure.
• Ace2 and Mas1 knockout mice exhibit impaired thermogenesis.
• ACE2 pathway activation ameliorated metabolic dysfunction in obese and diabetic models, enhancing white adipose tissue browning.
• Mechanistically, the ACE2 pathway activates Akt/FoxO1 and PKA, upregulating UCP1 and mitochondrial function.

Conclusions:

• The ACE2 pathway is a critical regulator of adaptive thermogenesis and energy expenditure.
• Modulating the ACE2 pathway shows promise for treating metabolic disorders like obesity and diabetes.
• Targeting the ACE2 pathway offers novel therapeutic strategies for improving metabolic health.