Brain-liver connections: role of the preautonomic PVN neurons

Abstract

O'Hare JD, Zsombok A. Brain-liver connections: role of the preautonomic PVN neurons. Am J Physiol Endocrinol Metab 310: E183-E189, 2016. First published December 8, 2015; doi:10.1152/ajpendo.00302.2015.-Diabetes mellitus and the coexisting conditions and complications, including hypo-and hyperglycemic events, obesity, high cholesterol levels, and many more, are devastating problems. Undoubtedly, there is a huge demand for treatment and prevention of these conditions that justifies the search for new approaches and concepts for better management of whole body metabolism. Emerging evidence demonstrates that the autonomic nervous system is largely involved in the regulation of glucose homeostasis; however, the underlying mechanisms are still under investigation. Within the hypothalamus, the paraventricular nucleus (PVN) is in a unique position to integrate neural and hormonal signals to command both the autonomic and neuroendocrine outflow. This minireview will provide a brief overview on the role of preautonomic PVN neurons and the importance of the PVN-liver pathway in the regulation of glucose homeostasis. paraventricular nucleus; liver-related neurons; glucose homeostasis DIABETES MELLITUS is the most common metabolic disorder. The National Diabetes Statistics Report from 2014 published by the Centers for Disease Control and Prevention (8a) estimated that 29.1 million people, which is 9.3% of the US population, suffer from diabetes mellitus. Even more alarming information is that the number of new diabetes cases showed an increase of 1.7 million within 2 yr, and in 2010 diabetes mellitus was listed as the seventh leading cause of death. The coexisting conditions and complications of diabetes mellitus are severe, including hypo-and hyperglycemic events, high blood pressure, obesity, high cholesterol levels, and many more. Undoubtedly, there is a huge demand for treatment and prevention of these conditions that justifies the search for new approaches and solutions for better management of whole body metabolism. One possibility, which has recently attracted more interest, is the role of the brain in the regulation of metabolism (46, 50), particularly the contribution of the autonomic nervous system (ANS) to metabolic control (51,69,73,75).The hypothalamus has been known as one of the critical brain structures that is involved in the regulation and coordination of homeostatic functions. Traditionally, the hypothalamus was appreciated for its neuroendocrine control system; however, its control over the ANS has also been recognized (17,46,51,69,75

Genetic deletion of the circadian clock transcription factor BMAL1 and chronic alcohol consumption differentially alter hepatic glycogen in mice

“…4 and 5). This interesting result supports the fact that extrahepatic factors, like hormones (in-sulin and glucocorticoids) or neural signals (hypothalamic) help maintain the glycogen rhythm (8,30,35), even when the liver clock has been genetically disrupted. Thus these novel findings suggest a "two-hit" mechanism for loss in the glycogen rhythm in alcohol-fed HBK mice, as alcohol alone or clock disruption alone was insufficient to abolish the glycogen rhythm.…”

Oxytocinergic Cells of the Hypothalamic Paraventricular Nucleus Are Involved in Food Entrainment

“…Furthermore, these authors, by using a similar strategy, also found preautonomic OTergic neurons in the posterior part of the PVN neurons that project to sympathetic or parasympathetic motor nuclei connected with the adrenal and liver, besides the pancreas (Buijs et al, 2003). In agreement, in vivo studies demonstrate that activation of sympathetic or parasympathetic innervation of the liver as well as pharmacological manipulation of preautonomic PVN neurons affects glucose homeostasis (O'Hare and Zsombok, 2016). These studies are very interesting in considering that in subjects under food restriction there is a shift in several hormonal and metabolic parameters to timing of feeding.…”

Circadian peak dopaminergic activity response at the biological clock pacemaker (suprachiasmatic nucleus) area mediates the metabolic responsiveness to a high‐fat diet

“…The neuronal connections from the SCN to the VMH and PVN include its indirect projections to the brain stem where noradrenergic nuclei provide the majority of noradrenergic input to the VMH and PVN . The SCN also sends strong projections directly to the PVN a neural centre with strong regulatory control over peripheral metabolism …”