Sympathetic NPY controls glucose homeostasis, cold tolerance, and cardiovascular functions in mice
Raniki Kumari,
Raluca Pascalau,
Hui Wang,
Sheetal Bajpayi,
Maria Yurgel,
Kwaku Quansah,
Samer Hattar,
Emmanouil Tampakakis,
Rejji Kuruvilla
Affiliations
Raniki Kumari
Department of Biology, Johns Hopkins University, Baltimore, MD 21218, USA
Raluca Pascalau
Department of Biology, Johns Hopkins University, Baltimore, MD 21218, USA
Hui Wang
Section on Light and Circadian Rhythms, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA
Sheetal Bajpayi
Division of Cardiology, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA
Maria Yurgel
Section on Light and Circadian Rhythms, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA
Kwaku Quansah
Department of Biology, Johns Hopkins University, Baltimore, MD 21218, USA; Division of Cardiology, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA
Samer Hattar
Section on Light and Circadian Rhythms, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA
Emmanouil Tampakakis
Division of Cardiology, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA
Rejji Kuruvilla
Department of Biology, Johns Hopkins University, Baltimore, MD 21218, USA; Corresponding author
Summary: 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.
