Sympathetic NPY controls glucose homeostasis, cold tolerance, and cardiovascular functions in mice.

Neuropeptide Y (NPY) is best known for its effects in the brain as an orexigenic and anxiolytic agent and in reducing energy expenditure. NPY is also co-expressed with norepinephrine (NE) in sympathetic neurons. Although NPY is generally considered to modulate noradrenergic responses, its specific roles in autonomic physiology remain under-appreciated. Here, we show that sympathetic-derived NPY is essential for metabolic and cardiovascular regulation in mice. NPY and NE are co-expressed in 90% of prevertebral sympathetic neurons and only 43% of paravertebral neurons. NPY-expressing neurons primarily innervate blood vessels in peripheral organs. Sympathetic-specific NPY deletion elicits pronounced metabolic and cardiovascular defects in mice, including reductions in insulin secretion, glucose tolerance, cold tolerance, and pupil size and elevated heart rate, while notably, however, basal blood pressure was unchanged. These findings provide insight into target tissue-specific functions of NPY derived from sympathetic neurons and imply its potential involvement in metabolic and cardiovascular diseases.

Sympathetic NPY controls glucose homeostasis, cold tolerance, and cardiovascular functions in mice.

Neuropeptide Y (NPY) is best known for its effects in the brain as an orexigenic and anxiolytic agent and in reducing energy expenditure. NPY is also co-expressed with Norepinephrine (NE) in sympathetic neurons. Although NPY is generally considered to modulate noradrenergic responses, its specific roles in autonomic physiology remain under-appreciated. Here, we show that sympathetic-derived NPY is essential for metabolic and cardiovascular regulation in mice. NPY and NE are co-expressed in 90% of prevertebral sympathetic neurons and only 43% of paravertebral neurons. NPY-expressing neurons primarily innervate blood vessels in peripheral organs. Sympathetic-specific deletion of NPY elicits pronounced metabolic and cardiovascular defects in mice, including reductions in insulin secretion, glucose tolerance, cold tolerance, pupil size, and an elevation in heart rate, while notably, however, basal blood pressure was unchanged. These findings provide new knowledge about target tissue-specific functions of NPY derived from sympathetic neurons and imply its potential involvement in metabolic and cardiovascular diseases.

The role of noncoding genetic variants in cardiomyopathy.

Cardiomyopathies remain one of the leading causes of morbidity and mortality worldwide. Environmental risk factors and genetic predisposition account for most cardiomyopathy cases. As with all complex diseases, there are significant challenges in the interpretation of the molecular mechanisms underlying cardiomyopathy-associated genetic variants. Given the technical improvements and reduced costs of DNA sequence technologies, an increasing number of patients are now undergoing genetic testing, resulting in a continuously expanding list of novel mutations. However, many patients carry noncoding genetic variants, and although emerging evidence supports their contribution to cardiac disease, their role in cardiomyopathies remains largely understudied. In this review, we summarize published studies reporting on the association of different types of noncoding variants with various types of cardiomyopathies. We focus on variants within transcriptional enhancers, promoters, intronic sites, and untranslated regions that are likely associated with cardiac disease. Given the broad nature of this topic, we provide an overview of studies that are relatively recent and have sufficient evidence to support a significant degree of causality. We believe that more research with additional validation of noncoding genetic variants will provide further mechanistic insights on the development of cardiac disease, and noncoding variants will be increasingly incorporated in future genetic screening tests.