The lateral parabrachial nucleus (
lPBN), located in the pons, is a well-recognized anorexigenic center harboring, amongst others, the
calcitonin gene-related peptide (CGRP)-expressing neurons that play a key role. The receptor for the orexigenic
hormone ghrelin (the
growth hormone secretagogue receptor, GHSR) is also abundantly expressed in the
lPBN and
ghrelin delivery to this site has recently been shown to increase food intake and alter food choice. Here we sought to explore whether GHSR-expressing cells in the
lPBN (GHSR
lPBN cells) contribute to feeding control, food choice and
body weight gain in mice offered an obesogenic diet, involving studies in which GHSR
lPBN cells were silenced. We also explored the neurochemical identity of GHSR
lPBN cells. To silence GHSR
lPBN cells, Ghsr-IRES-Cre male mice were bilaterally injected intra-
lPBN with a Cre-dependent viral vector expressing
tetanus toxin-light chain. Unlike control wild-type littermates that significantly increased in
body weight on the obesogenic diet (i.e., high-fat high-
sugar free choice diet comprising chow,
lard and 9%
sucrose solution), the heterozygous mice with silenced GHSR
lPBN cells were resistant to diet-induced
weight gain with significantly lower food intake and fat weight. The lean phenotype appeared to result from a decreased food intake compared to controls and caloric efficiency was unaltered. Additionally, silencing the GHSR
lPBN cells altered food choice, significantly reducing palatable food consumption. RNAscope and immunohistochemical studies of the
lPBN revealed considerable co-expression of GHSR with
glutamate and pituitary
adenylate cyclase-activating
peptide (
PACAP), and much less with
neurotensin,
substance P and CGRP. Thus, the GHSR
lPBN cells are important for diet-induced
weight gain and adiposity, as well as in the regulation of food intake and food choice. Most GHSR
lPBN cells were found to be glutamatergic and the majority (76%) do not belong to the well-characterized anorexigenic CGRP cell population.