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Chronic Low‐Dose ICV Infusion of Agrp in Mice May Suppress Indices of Resting Metabolism in Brown Adipose Tissue Independent of Effects on Feeding Behavior
Author(s) -
Oliveira Vanessa,
Balapattabi Kirthikaa,
Patil Chetan N.,
Hei Megan Vande,
Silva Sebastião D.,
Reho John J.,
Sigmund Curt D.,
Grobe Justin L.
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.02254
Subject(s) - brown adipose tissue , medicine , endocrinology , adipose tissue , food intake , dosing , chemistry
Agouti‐related peptide (Agrp) acts within in the central nervous system to stimulate feeding behavior and suppress energy expenditure, which results in body weight gain. Acute and chronic intracerebroventricular (ICV) administration of recombinant Agrp (0.2 to 1.0 nmol/d) induces hyperphagia in rats (Wissig et al. 2003; Tallam et al. 2004), but studies in mice are lacking. Therefore, we tested the effects of this route and range of infusion doses upon food intake, body mass, and adiposity in wildtype male C57BL/6J mice (Jackson Labs, 10–12 wk). Mice were implanted with chronic indwelling ICV cannulae connected to osmotic minipumps (Alzet) to deliver artificial cerebrospinal fluid vehicle (n=6), or 0.1 nmol/d (n=8) or 1.0 nmol/d (n=6) recombinant Agrp(82–132) peptide for 21 days. Unexpectedly, despite the efficacy of these dosing schedules published in rats, these infusion rates had no effect on food intake, body mass, or overall body composition (by NMR) in the present cohort of mice. Interestingly, interscapular “brown” adipose tissue (BAT) was hypertrophied in mice infused with the lower dose of Agrp (aCSF: 0.07±0.01 mg, Agrp 0.1 nmol/d: 0.10±0.01, Agrp 1.0 nmol/d: 0.09±0.01 (mean±sem); p<0.05 by ANOVA), and this difference remained after correction by body mass or tibia length. Although underpowered to detect statistically significant changes with the limited sample size, physiologically relevant trends toward reduction in the mRNA expression of Ucp1 (0.75 (0.92–0.62) fold of aCSF (±1 sem), n=5), Adrb3 (0.65 (0.74–0.57), n=7), and Dio2 (0.49 (0.8–0.42), n=6) were observed in the BAT from mice receiving 1.0 nmol/d Agrp. We conclude that the effects of ICV Agrp on BAT mass (and possible effects on thermogenic gene expression profiles in BAT) are independent of changes in feeding behavior in male C57BL/6J mice. These findings support species‐specific differences in sensitivity to ICV Agrp, and suggest that Agrp influences resting energy expenditure independently from its effects on feeding behavior. Support or Funding Information HL134850, HL084207