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Maternal obesity impairs fetal mitochondriogenesis and brown adipose tissue development partially via upregulation of miR-204-5p.

ABSTRACT: Maternal obesity (MO) predisposes offspring to metabolic disorders, but the mechanisms remain poorly defined. Recent studies emphasize the importance of brown adipose tissue (BAT) in maintaining metabolic health, and MO was recently demonstrated to impair BAT thermogenic function in offspring. The current study aimed to investigate the mechanisms leading to the impairment in fetal BAT development due to MO. Female C57BL/6J mice were fed a control diet or a 60% high-fat diet for 10?weeks, mated and maintained on their respective diets during pregnancy. Fetal tissue was collected at E18.5, the late stage of pregnancy. Fetal BAT contained more triglycerides compared to the control, which was correlated with higher expression of white adipogenic markers. On the other hand, the expression of BAT markers was down-regulated in the MO fetal BAT. Based on RNA-sequencing analyses, genes related to mitochondriogenesis and myogenesis were found to be down-regulated, while those related to white adipocyte differentiation were up-regulated in MO fetal BAT. Because brown adipocytes are derived from myogenic progenitors, the down-regulation of myogenic genes might partially explain hampered brown adipogenesis in MO fetal BAT. Consistently, mitochondrial DNA and mitochondrial biogenesis markers were also down-regulated in MO fetal BAT. MicroRNA-sequencing identified that miR-204-5p expression was elevated in MO fetal BAT. This microRNA targeted the 3'-untranslated regions of PGC1? and Sirt1 mRNA to suppress their expression and impair mitochondriogenesis. In summary, MO impaired fetal BAT development through suppressing myogenesis and brown adipogenesis while enhancing white adipogenic commitment, and inhibited mitochondriogenesis partially through enhancing miR-204-5p expression.

SUBMITTER: Wang H

PROVIDER: S-EPMC6708788 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Maternal obesity impairs fetal mitochondriogenesis and brown adipose tissue development partially via upregulation of miR-204-5p.

Wang Hanning H Chen Yanting Y Mao Xueying X Du Min M

Biochimica et biophysica acta. Molecular basis of disease 20190724 10

Maternal obesity (MO) predisposes offspring to metabolic disorders, but the mechanisms remain poorly defined. Recent studies emphasize the importance of brown adipose tissue (BAT) in maintaining metabolic health, and MO was recently demonstrated to impair BAT thermogenic function in offspring. The current study aimed to investigate the mechanisms leading to the impairment in fetal BAT development due to MO. Female C57BL/6J mice were fed a control diet or a 60% high-fat diet for 10 weeks, mated a ...[more]

PMID: 31351130

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Project description:BackgroundBrown adipose tissue (BAT) is specialized to dissipate energy in the form of heat. BAT-mediated heat production in rodents and humans is critical for effective temperature adaptation of newborns to the extrauterine environment immediately after birth. However, very little is known about whether and how fetal BAT development is modulated in-utero in response to changes in maternal thermal environment during pregnancy. Using BL6 mice, we evaluated the impact of different maternal environmental temperatures (28 °C and 18 °C) on the transcriptome of the placenta and fetal BAT to test if maternal cold exposure influences fetal BAT development via placental remodeling.ResultsMaternal weight gain during pregnancy, the average number of fetuses per pregnancy, and placental weight did not differ between the groups at 28 °C and 18 °C. However, the average fetal weight at E18.5 was 6% lower in the 18 °C-group compared to the 28 °C-group. In fetal BATs, cold exposure during pregnancy induced increased expression of genes involved in de novo lipogenesis and lipid metabolism while decreasing the expression of genes associated with muscle cell differentiation, thus suggesting that maternal cold exposure may promote fetal brown adipogenesis by suppressing the myogenic lineage in bidirectional progenitors. In placental tissues, maternal cold exposure was associated with upregulation of genes involved in complement activation and downregulation of genes related to muscle contraction and actin-myosin filament sliding. These changes may coordinate placental adaptation to maternal cold exposure, potentially by protecting against cold stress-induced inflammatory damage and modulating the vascular and extravascular contractile system in the placenta.ConclusionsThese findings provide evidence that environmental cold temperature sensed by the mother can modulate the transcriptome of placental and fetal BAT tissues. The ramifications of the observed gene expression changes warrant future investigation.

Dataset Information

Maternal obesity impairs fetal mitochondriogenesis and brown adipose tissue development partially via upregulation of miR-204-5p.

Publications

Maternal obesity impairs fetal mitochondriogenesis and brown adipose tissue development partially via upregulation of miR-204-5p.

Similar Datasets

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