ACE2/Angiotensin 1-7/Mas Receptor Axis in Thermogenic Adipose Tissue: Age-Related Implications for Pediatric Obesity.

Pediatric obesity is a growing global health challenge, and effective and sustainable therapeutic options remain limited. Although lifestyle modifications remain the cornerstone of treatment, pharmacological and surgical interventions are restricted among pediatric populations, highlighting the need for novel pathophysiology-based strategies. Increasing evidence indicates that the renin-angiotensin system, particularly the nonclassical angiotensin-converting enzyme 2 (ACE2)/angiotensin 1-7 (Ang1-7)/Mas receptor (MasR) axis, plays an important role in metabolic regulation beyond classical cardiovascular functions. The ACE2/Ang1-7/MasR axis exerts pleiotropic metabolic effects, including anti-inflammatory and insulin-sensitizing actions, and has emerged as a key regulator of adipose tissue biology. Experimental studies have demonstrated that activation of this pathway stimulates brown adipose tissue (BAT), induces browning of white adipose tissue (WAT), and increases energy expenditure, thereby attenuating diet-induced obesity and attracting considerable attention as potential therapeutic targets. However, accumulating evidence from human imaging studies and experimental models suggests that BAT activity and thermogenic plasticity decline with age, which may affect the metabolic efficacy of interventions targeting thermogenic adipose tissue. Age-related differences in adipose tissue responsiveness may therefore contribute to discrepancies among previous studies examining Ang1-7-mediated thermogenic effects. This review summarized the current evidence regarding the role of the ACE2/Ang1-7/MasR axis in regulating thermogenic adipose tissue, with a focus on BAT activation and WAT browning in obesity. We further discuss age-related considerations that may modulate responsiveness to this pathway. Given that BAT activity is intrinsically high during childhood and adolescence, ACE2/Ang1-7 axis modulation may represent a promising therapeutic strategy for pediatric obesity.