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Sympathetic innervation of interscapular brown adipose tissue is not a predominant mediator of oxytocin-elicited reductions of body weight and adiposity in male diet-induced obese mice.
- Source :
-
Frontiers in endocrinology [Front Endocrinol (Lausanne)] 2024 Jul 31; Vol. 15, pp. 1440070. Date of Electronic Publication: 2024 Jul 31 (Print Publication: 2024). - Publication Year :
- 2024
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Abstract
- Previous studies indicate that CNS administration of oxytocin (OT) reduces body weight in high fat diet-induced obese (DIO) rodents by reducing food intake and increasing energy expenditure (EE). We recently demonstrated that hindbrain (fourth ventricular [4V]) administration of OT elicits weight loss and elevates interscapular brown adipose tissue temperature (T <subscript>IBAT</subscript> , a surrogate measure of increased EE) in DIO mice. What remains unclear is whether OT-elicited weight loss requires increased sympathetic nervous system (SNS) outflow to IBAT. We hypothesized that OT-induced stimulation of SNS outflow to IBAT contributes to its ability to activate BAT and elicit weight loss in DIO mice. To test this hypothesis, we determined the effect of disrupting SNS activation of IBAT on the ability of 4V OT administration to increase T <subscript>IBAT</subscript> and elicit weight loss in DIO mice. We first determined whether bilateral surgical SNS denervation to IBAT was successful as noted by ≥ 60% reduction in IBAT norepinephrine (NE) content in DIO mice. NE content was selectively reduced in IBAT at 1-, 6- and 7-weeks post-denervation by 95.9 ± 2.0, 77.4 ± 12.7 and 93.6 ± 4.6% ( P <0.05), respectively and was unchanged in inguinal white adipose tissue, pancreas or liver. We subsequently measured the effects of acute 4V OT (1, 5 µg ≈ 0.99, 4.96 nmol) on T <subscript>IBAT</subscript> in DIO mice following sham or bilateral surgical SNS denervation to IBAT. We found that the high dose of 4V OT (5 µg ≈ 4.96 nmol) elevated T <subscript>IBAT</subscript> similarly in sham mice as in denervated mice. We subsequently measured the effects of chronic 4V OT (16 nmol/day over 29 days) or vehicle infusions on body weight, adiposity and food intake in DIO mice following sham or bilateral surgical denervation of IBAT. Chronic 4V OT reduced body weight by 5.7 ± 2.23% and 6.6 ± 1.4% in sham and denervated mice ( P <0.05), respectively, and this effect was similar between groups ( P =NS). OT produced corresponding reductions in whole body fat mass ( P <0.05). Together, these findings support the hypothesis that sympathetic innervation of IBAT is not necessary for OT-elicited increases in BAT thermogenesis and reductions of body weight and adiposity in male DIO mice.<br />Competing Interests: JB had a financial interest in OXT Therapeutics, Inc., a company developing highly specific and stable analogs of oxytocin to treat obesity and metabolic disease. The authors’ interests were reviewed and are managed by their local institutions in accordance with their conflict of interest policies. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.<br /> (Copyright © 2024 Edwards, Nguyen, Dodson, Herbertson, Wolden-Hanson, Wietecha, Honeycutt, Slattery, O’Brien, Graham, Havel, Mundinger, Sikkema, Peskind, Ryu, Taborsky and Blevins.)
- Subjects :
- Animals
Male
Mice
Body Weight drug effects
Weight Loss drug effects
Mice, Obese
Energy Metabolism drug effects
Norepinephrine metabolism
Oxytocin pharmacology
Adipose Tissue, Brown drug effects
Adipose Tissue, Brown metabolism
Adipose Tissue, Brown innervation
Obesity metabolism
Sympathetic Nervous System drug effects
Diet, High-Fat adverse effects
Adiposity drug effects
Mice, Inbred C57BL
Subjects
Details
- Language :
- English
- ISSN :
- 1664-2392
- Volume :
- 15
- Database :
- MEDLINE
- Journal :
- Frontiers in endocrinology
- Publication Type :
- Academic Journal
- Accession number :
- 39145314
- Full Text :
- https://doi.org/10.3389/fendo.2024.1440070