Dataset Information

ADORA₁-driven brain-sympathetic neuro-adipose connections control body weight and adipose lipid metabolism.

ABSTRACT: It is essential to elucidate brain-adipocyte interactions in order to tackle obesity and its comorbidities, as the precise control of brain-adipose tissue cross-talk is crucial for energy and glucose homeostasis. Recent studies show that in the peripheral adipose tissue, adenosine induces adipogenesis through peripheral adenosine A₁ receptor (pADORA₁) signaling; however, it remains unclear whether systemic and adipose tissue metabolism would also be under the control of central (c) ADORA₁ signaling. Here, we use tissue-specific pharmacology and metabolic tools to clarify the roles of cADORA₁ signaling in energy and adipocyte physiology. We found that cADORA₁ signaling reduces body weight while also inducing adipose tissue lipolysis. cADORA₁ signaling also increases adipose tissue sympathetic norepinephrine content. In contrast, pADORA₁ signaling facilitates a high-fat diet-induced obesity (DIO). We propose here a novel mechanism in which cADORA₁ and pADORA₁ signaling hinder and aggravate DIO, respectively.

SUBMITTER: Zhang J

PROVIDER: S-EPMC8050129 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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Publications

ADORA1-driven brain-sympathetic neuro-adipose connections control body weight and adipose lipid metabolism.

Zhang Jia J Hou Yanjun Y Du Xue-Liang XL Chen Dan D Sui Guangzhi G Qi Yong Y Licinio Julio J Wong Ma-Li ML Yang Yunlei Y

Molecular psychiatry 20201016 7

It is essential to elucidate brain-adipocyte interactions in order to tackle obesity and its comorbidities, as the precise control of brain-adipose tissue cross-talk is crucial for energy and glucose homeostasis. Recent studies show that in the peripheral adipose tissue, adenosine induces adipogenesis through peripheral adenosine A1 receptor (pADORA1) signaling; however, it remains unclear whether systemic and adipose tissue metabolism would also be under the control of cen ...[more]

PMID: 33067580

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Project description: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 (TIBAT, 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 TIBAT 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 TIBAT 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 TIBAT 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.

Dataset Information

ADORA₁-driven brain-sympathetic neuro-adipose connections control body weight and adipose lipid metabolism.

Publications

ADORA<sub>1</sub>-driven brain-sympathetic neuro-adipose connections control body weight and adipose lipid metabolism.

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