β2-Adrenergic receptor desensitization in perirenal adipose tissue in fetuses and lambs with placental insufficiency-induced intrauterine growth restriction

Xiaochuan Chen, Anna L. Fahy, Alice S. Green, Miranda J. Anderson, Robert P. Rhoads, Sean W Limesand

Research output: Contribution to journalArticle

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Abstract

Placental insufficiency-induced intrauterine growth restriction (IUGR) fetuses have chronic hypoxaemia and elevated plasma catecholamine concentrations. In this study, we determined whether adrenergic responsiveness becomes desensitized in the perirenal adipose tissue of IUGR fetuses and lambs by measuring adrenergic receptor (AR) mRNA and protein levels. We also tested the ability of adrenaline to mobilize non-esterified fatty acids (NEFAs) in young lambs. Perirenal adipose tissue was collected from IUGR and control fetuses at 133 days of gestational age (dGA) and lambs at 18 days of age (dA) β2-AR mRNA concentrations were 59% and 74% lower (P < 0.05) in IUGR fetuses and lambs compared to controls, respectively, which also resulted in lower protein levels (P < 0.05). No treatment differences were detected for α1A-, α1B-, α1D-, α2A-, α2B-, α2C-, β1- and β3-AR expression. mRNA concentrations were also determined for hormone sensitive lipase (HSL), perilipin (lipid droplet-associated protein), and two adipokines, leptin and adiponectin. Adiponectin and HSL were not different between treatments at either age. Compared to controls, perilipin and leptin mRNA concentrations were lower (P < 0.05) in IUGR fetuses but not in lambs. Because of the β2-AR results, we challenged a second cohort of lambs with exogenous adrenaline at 21 dA. The ability of adrenaline to mobilize NEFA was 55 ± 15% lower (P < 0.05) in IUGRs than controls. Collectively, our findings indicate that elevated catecholamine exposure in utero causes desensitization of adipose tissue by down-regulation of β2-AR, and this persists in lambs. This impairment in adrenergic stimulated lipolysis might partially explain early onset obesity in IUGR offspring.

Original languageEnglish (US)
Pages (from-to)3539-3549
Number of pages11
JournalJournal of Physiology
Volume588
Issue number18
DOIs
StatePublished - Sep 2010

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Placental Insufficiency
Adrenergic Receptors
Adipose Tissue
Fetus
Growth
Epinephrine
Sterol Esterase
Messenger RNA
Adiponectin
Leptin
Adrenergic Agents
Catecholamines
Fatty Acids
Adipokines
Fetal Growth Retardation
Lipolysis
Gestational Age
Proteins
Down-Regulation
Obesity

ASJC Scopus subject areas

  • Physiology

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β2-Adrenergic receptor desensitization in perirenal adipose tissue in fetuses and lambs with placental insufficiency-induced intrauterine growth restriction. / Chen, Xiaochuan; Fahy, Anna L.; Green, Alice S.; Anderson, Miranda J.; Rhoads, Robert P.; Limesand, Sean W.

In: Journal of Physiology, Vol. 588, No. 18, 09.2010, p. 3539-3549.

Research output: Contribution to journalArticle

Chen, Xiaochuan ; Fahy, Anna L. ; Green, Alice S. ; Anderson, Miranda J. ; Rhoads, Robert P. ; Limesand, Sean W. / β2-Adrenergic receptor desensitization in perirenal adipose tissue in fetuses and lambs with placental insufficiency-induced intrauterine growth restriction. In: Journal of Physiology. 2010 ; Vol. 588, No. 18. pp. 3539-3549.
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