1. Adiponectin links maternal metabolism to uterine contractility
- Author
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Thomas Jansson, Vibhuti Vyas, K. Joseph Hurt, Rachael Bok, Theresa L. Powell, and Damian D. Guerra
- Subjects
Adult ,0301 basic medicine ,medicine.medical_specialty ,Adipose tissue ,Biochemistry ,Uterine contractility ,Mice ,03 medical and health sciences ,0302 clinical medicine ,AMP-Activated Protein Kinase Kinases ,Pregnancy ,Internal medicine ,Genetics ,medicine ,Animals ,Humans ,Molecular Biology ,Adiponectin ,business.industry ,Research ,Myometrium ,nutritional and metabolic diseases ,Insulin sensitivity ,Maternal metabolism ,Middle Aged ,Mice, Inbred C57BL ,030104 developmental biology ,Endocrinology ,Increased risk ,Oxytocin ,Female ,Receptors, Adiponectin ,business ,Protein Kinases ,hormones, hormone substitutes, and hormone antagonists ,030217 neurology & neurosurgery ,Muscle Contraction ,Biotechnology ,medicine.drug - Abstract
Adiponectin is secreted by adipose tissue and promotes insulin sensitivity. Low circulating adiponectin is associated with increased risk for preterm labor, but the influence of adiponectin on uterine myometrial physiology is unknown. We hypothesized that adiponectin receptors (AdipoRs) decrease myometrial contractility via AMPK to promote uterine quiescence in pregnancy. Using quantitative RT-PCR, we found that nonpregnant or pregnant human and mouse myometrium express AdipoR1 and AdipoR2 mRNAs. We confirmed AdipoR2 protein expression in human and mouse myometrium, with increased abundance in late mouse pregnancy. Both recombinant adiponectin and a pharmacologic AdipoR agonist, AdipoRon, potently inhibited uterine myometrial strip contractions in physiologic organ bath. The relaxation was independent of contractile stimulus (oxytocin, KCl, U46619). AdipoR agonists increased AMPK phosphorylation in pregnant mouse myometrium, and the direct AMPK activator A769662 also relaxed myometrial strips. However, the AMPK inhibitor dorsomorphin (compound C) blocked AMPK phosphorylation but did not abolish relaxation with either AdipoRon or A769662. In summary, adiponectin inhibits myometrial contractility consistent with the possibility that it is a previously unrecognized link between maternal metabolism and pregnancy maintenance. We also identify a separate role for AMPK regulating myometrial contractions that may influence labor onset.—Vyas, V., Guerra, D. D., Bok, R., Powell, T., Jansson, T., Hurt, K. J. Adiponectin links maternal metabolism to uterine contractility.
- Published
- 2019
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