Alpha2delta-1 in SF1+ Neurons of the Ventromedial Hypothalamus Is an Essential
Regulator of Glucose and Lipid Homeostasis.
Authors Felsted JA, Chien CH, Wang D, Panessiti M, Ameroso D, Greenberg A, Feng G, Kong
D, Rios M
Submitted By Submitted Externally on 1/3/2018
Status Published
Journal Cell reports
Year 2017
Date Published 12/1/2017
Volume : Pages 21 : 2737 - 2747
PubMed Reference 29212022
Abstract The central mechanisms controlling glucose and lipid homeostasis are
inadequately understood. We show that a2d-1 is an essential regulator of glucose
and lipid balance, acting in steroidogenic factor-1 (SF1) neurons of the
ventromedial hypothalamus (VMH). These effects are body weight independent and
involve regulation of SF1+ neuronal activity and sympathetic output to metabolic
tissues. Accordingly, mice with a2d-1 deletion in SF1 neurons exhibit glucose
intolerance, altered lipolysis, and decreased cholesterol content in adipose
tissue despite normal energy balance regulation. Profound reductions in the
firing rate of SF1 neurons, decreased sympathetic output, and elevated
circulating levels of serotonin are associated with these alterations. Normal
calcium currents but reduced excitatory postsynaptic currents in mutant SF1
neurons implicate a2d-1 in the promotion of excitatory synaptogenesis separate
from its canonical role as a calcium channel subunit. Collectively, these
findings identify an essential mechanism that regulates VMH neuronal activity
and glycemic and lipid control and may be a target for tackling metabolic