Sex-specific regulation of miR-22 and ERα in white adipose tissue of obese dam's female offspring impairs the early postnatal development of functional beige adipocytes in mice.

Autor: de Sousa É; Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil., de Mendonça M; Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil., Bolin AP; Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil., de Oliveira NP; Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil., Real CC; Department of Radiology, Medical School, University of Sao Paulo, São Paulo, SP, Brazil., Hu X; Department of Cardiology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA., Huang ZP; Department of Cardiology, Center for Translational Medicine, Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China., Wang DZ; Department of Cardiology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA., Rodrigues AC; Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil. Electronic address: alice-rodrigues@usp.br.
Jazyk: angličtina
Zdroj: Biochimica et biophysica acta. Molecular basis of disease [Biochim Biophys Acta Mol Basis Dis] 2024 Apr; Vol. 1870 (4), pp. 167057. Date of Electronic Publication: 2024 Feb 07.
DOI: 10.1016/j.bbadis.2024.167057
Abstrakt: During inguinal adipose tissue (iWAT) ontogenesis, beige adipocytes spontaneously appear between postnatal 10 (P10) and P20 and their ablation impairs iWAT browning capacity in adulthood. Since maternal obesity has deleterious effects on offspring iWAT function, we aimed to investigate its effect in spontaneous iWAT browning in offspring. Female C57BL/6 J mice were fed a control or obesogenic diet six weeks before mating. Male and female offspring were euthanized at P10 and P20 or weaned at P21 and fed chow diet until P60. At P50, mice were treated with saline or CL316,243, a β3-adrenoceptor agonist, for ten days. Maternal obesity induced insulin resistance at P60, and CL316,243 treatment effectively restored insulin sensitivity in male but not female offspring. This discrepancy occurred due to female offspring severe browning impairment. During development, the spontaneous iWAT browning and sympathetic nerve branching at P20 were severely impaired in female obese dam's offspring but occurred normally in males. Additionally, maternal obesity increased miR-22 expression in the iWAT of male and female offspring during development. ERα, a target and regulator of miR-22, was concomitantly upregulated in the male's iWAT. Next, we evaluated miR-22 knockout (KO) offspring at P10 and P20. The miR-22 deficiency does not affect spontaneous iWAT browning in females and, surprisingly, anticipates iWAT browning in males. In conclusion, maternal obesity impairs functional iWAT development in the offspring in a sex-specific way that seems to be driven by miR-22 levels and ERα signaling. This impacts adult browning capacity and glucose homeostasis, especially in female offspring.
Competing Interests: Declaration of competing interest The authors declare that the research was conducted without commercial or financial relationships that could be considered a potential conflict of interest.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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