Role of adropin in arterial stiffening associated with obesity and type 2 diabetes

Abstract

Adropin is a peptide largely secreted by the liver and known to regulate energy homeostasis; however, it also exerts cardiovascular effects. Herein, we tested the hypothesis that low circulating levels of adropin in obesity and type 2 diabetes (T2D) contribute to arterial stiffening. In support of this hypothesis, we report that obesity and T2D is associated with reduced levels of adropin (in liver and plasma) and increased arterial stiffness in mice and humans. Establishing causation, we show that mesenteric arteries from adropin knockout mice are also stiffer, relative to arteries from wild-type counterparts, thus recapitulating the stiffening phenotype observed in T2D db/db mice. Given the above, we performed a set of follow-up experiments, in which we found that: 1) exposure of endothelial cells or isolated mesenteric arteries from db/db mice to adropin reduces filamentous actin (F-actin) stress fibers and stiffness; 2) adropin-induced reduction of F-actin and stiffness in endothelial cells and db/db mesenteric arteries is abrogated by inhibition of nitric oxide (NO) synthase; and 3) stimulation of smooth muscle cells or db/db mesenteric arteries with a NO mimetic reduces stiffness. Last, we demonstrated that in vivo treatment of db/db mice with adropin for four weeks reduces stiffness in mesenteric arteries. Collectively, these findings indicate that adropin can regulate arterial stiffness, likely via endothelial-derived NO, and thus support the notion that "hypoadropinemia" should be considered as a putative target for the prevention and treatment of arterial stiffening in obesity and T2D.

Low circulating adropin concentrations predict increased risk of cognitive decline in community-dwelling older adults

“…Circulating adropin levels correlate with vascular function. (7-10) Analysis of standing and prone heart rate and blood pressure recorded on the same visit used to collect the plasma samples used for adropin measurement suggested a relationship. Simple modelling indicated a positive correlation between heart rate measured in the standing (π=0.159, P<0.001, N=448) or prone positions (ρ=0.105, P<0.05, N=447).…”

Low circulating adropin levels in late-middle aged African Americans with poor cognitive performance

“…In this study, low serum adropin concentrations did not correlate with severe obesity, diabetes, or systemic markers of inflammation or neuropathy. Recent experiments using mice and cultured cells indicate that deficits in cerebrovascular blood flow, protection of the blood brain barrier, and synaptic functions could be involved 3,5,7,8,30,32 .…”

“…Circulating levels of adropin correlate with indices of glucose and lipid metabolism [1][2][3][4] . Here we also observed correlations between serum adropin concentrations and serum indices of metabolic homeostasis.…”

“…Circulating levels of adropin, a low molecular weight peptide hormone, correlate with vascular tone, glucose metabolism, and hepatic lipid metabolism [1][2][3][4] . The primary source of adropin in the circulation is not known.…”

Adropin Predicts Chronic Kidney Disease in Type 2 Diabetes Mellitus Patients with Chronic Heart Failure

“…The clinical significance of adropin levels in different patient populations remains controversial. There is numerous evidence that overweight/obese/T2DM patients had lower adropin levels than healthy volunteers and that a decreased adropin level was associated with a risk of renal dysfunction in patients with T2DM [ 21 , 22 , 23 , 24 ]. Another study reported that elevated serum levels of adropin correlated with a low risk of carotid atherosclerosis in T2DM patients [ 25 ].…”