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Lack of NPY in neurotensin neurons leads to a lean phenotype

Abstract

Neuropeptide Y (NPY) producing neurons in the arcuate nucleus (Arc) of the hypothalamus are essential to the regulation of food intake and energy homeostasis. Whilst they have classically been thought to co-express agouti-related peptide (AgRP), it is now clear that there is a sub-population of NPY neurons in the Arc that do not. Here, we show that a subset of AgRP-negative, NPY-positive neurons in the Arc also express neurotensin (NTS) and we use an NTS-Cre line to investigate the function of this sub-population of NPY neurons. The lack of NPY in NTS-positive neurons led to a marked reduction in fat mass and bodyweight as well as a significant reduction in food intake in male NPY(lox/lox); NTS(cre/+) mice compared to controls. Despite the reduction in food intake, overall energy expenditure was similar between genotypes due to concomitant reduction in activity in NPY(lox/lox); NTS(cre/+) mice. Furthermore, cortical bone mass was significantly reduced in NPY(lox/lox);NTS(cre/+) mice with no evident alterations in the cancellous bone compartment, likely due to reduced leptin levels as a result of their reduced adiposity. Taken together, these data suggest that the sub-population of Arc NPY neurons expressing NTS are critical for regulating food intake, activity and fat mass but are not directly involved in the control of bone mass.

Type Journal
ISBN 1532-2785 (Electronic) 0143-4179 (Linking)
Authors Lee, N. J.; Qi, Y.; Enriquez, R. F.; Ip, C. K.; Herzog, H.
Responsible Garvan Author Prof Herbert Herzog
Publisher Name NEUROPEPTIDES
Published Date 2019-11-12
Published Pages 101994
Status Always Electronic
DOI 10.1016/j.npep.2019.101994
URL link to publisher's version https://www.ncbi.nlm.nih.gov/pubmed/31740068