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Publication
Hypothalamic growth hormone receptor (GHR) controls hepatic glucose production
in nutrient-sensing leptin receptor (LepRb) expressing neurons.
Authors Cady G, Landeryou T, Garratt M, Kopchick JJ, Qi N, Garcia-Galiano D, Elias CF,
Myers MG, Miller RA, Sandoval DA, Sadagurski M
Submitted By Submitted Externally on 4/24/2018
Status Published
Journal Molecular metabolism
Year 2017
Date Published 5/1/2017
Volume : Pages 6 : 393 - 405
PubMed Reference 28462074
Abstract The GH/IGF-1 axis has important roles in growth and metabolism. GH and GH
receptor (GHR) are active in the central nervous system (CNS) and are crucial in
regulating several aspects of metabolism. In the hypothalamus, there is a high
abundance of GH-responsive cells, but the role of GH signaling in hypothalamic
neurons is unknown. Previous work has demonstrated that the Ghr gene is highly
expressed in LepRb neurons. Given that leptin is a key regulator of energy
balance by acting on leptin receptor (LepRb)-expressing neurons, we tested the
hypothesis that LepRb neurons represent an important site for GHR signaling to
control body homeostasis., To determine the importance of GHR signaling in LepRb
neurons, we utilized Cre/loxP technology to ablate GHR expression in LepRb
neurons (LeprEYFP?GHR). The mice were generated by crossing the Leprcre on the
cre-inducible ROSA26-EYFP mice to GHRL/L mice. Parameters of body composition
and glucose homeostasis were evaluated., Our results demonstrate that the sites
with GHR and LepRb co-expression include ARH, DMH, and LHA neurons. Leptin
action was not altered in LeprEYFP?GHR mice; however, GH-induced pStat5-IR in
LepRb neurons was significantly reduced in these mice. Serum IGF-1 and GH levels
were unaltered, and we found no evidence that GHR signaling regulates food
intake and body weight in LepRb neurons. In contrast, diminished GHR signaling
in LepRb neurons impaired hepatic insulin sensitivity and peripheral lipid
metabolism. This was paralleled with a failure to suppress expression of the
gluconeogenic genes and impaired hepatic insulin signaling in LeprEYFP?GHR
mice., These findings suggest the existence of GHR-leptin neurocircuitry that
plays an important role in the GHR-mediated regulation of glucose metabolism
irrespective of feeding.




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