Adipocyte-specific deletion of adrenomedullin exacerbates high-fat diet-induced hypertension.

Abstract

Adrenomedullin (AM) is highly expressed in cardiovascular tissues and has been extensively studied as a vasoactive peptide. Subsequent studies have also demonstrated substantial AM expression in adipose tissue; however, the pathophysiological role of adipocyte-derived AM in obesity remains unclear. We generated adipocyte-specific AM knockout mice (Adiponectin-Cre; Adm^fl/fl, cKO) and fed cKO and littermate controls normal chow (NC) or HFD from 8 to 36 weeks of age. HFD increased systolic blood pressure (SBP) in both genotypes, but SBP was higher in cKO mice under chronic HFD conditions, despite no genotype-dependent difference in body weight. Circulating AM increased with HFD in both groups but remained lower in cKO mice. Plasma renin concentration did not differ by diet or genotype, whereas aldosterone increased with HFD without significant genotype-dependent differences. Urinary epinephrine and norepinephrine were unchanged, whereas an HFD-associated increase in urinary dopamine observed in controls was attenuated in cKO mice. Together, these data suggest that adipocyte-derived AM mitigates HFD-associated hypertension and may be linked to renal dopaminergic responses during chronic metabolic stress.