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Sexual dimorphism in thermogenic regulators and metrnl expression in adipose tissue of offspring mice exposed to maternal and postnatal overnutrition

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Abstract

Current study investigated the impact of maternal and postnatal overnutrition on phenotype of adipose, in relation to offspring thermogenesis and sex. Female C57BL/6 J mice were fed with CHOW or high fat diet (HFD) for 2 weeks before mating, throughout gestation and lactation. At weaning, pups were fed to 9 weeks old with CHOW or HFD, which resulted in four groups for each gender——male or female: CHOW-CHOW (CC), CHOW-HFD (CH), HFD-CHOW (HC), HFD-HFD (HH). Maternal and post-weaning HFD enhanced thermogenic factors such as Acox1, Dio2 and Cox8b in iBAT of male and female offspring, but increased SIRT1, PGC-1α and UCP1 only in female. However, Acox1, Dio2 and Cox8b mRNA expression and SIRT1, PGC-1α and UCP1 protein expression were only enhanced upon maternal and post-weaning HFD in sWAT and pWAT of female offspring. Increased metrnl expression in adipose were observed in sex- and depot-specific manner, while enhanced circulating metrnl level was only observed in male offspring undergoing maternal HFD. Palmitic acid changed metrnl expression during preadipocytes differentiation and siRNA-mediated knockdown of metrnl inhibited preadipocyte differentiation. Female offspring were more prone to resist adverse outcomes induced by maternal and post-weaning overnutrition, which probably related to metrnl expression and thermogenesis.

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Data availability

All raw data that support the findings of this study will be available without restriction from the corresponding author on reasonable request.

Abbreviations

Acox1 :

Acyl-coenzyme A oxidase 1

A MPKα :

Adenosine 5 ‘-monophosphate (AMP)-activated protein kinase α

BW:

Body weight

BMI:

Body mass index

CAD:

Coronary artery disease

CHO:

Cholesterol

Cox8b :

Cytochrome c oxidase subunit VIIIb

Dio2 :

The type 2 iodothyronine deiodinase

Fabp4 :

Fatty Acid Binding Protein 4

GDM:

Gestational diabetes mellitus

GOT:

Glutamate-oxaloacetate transaminase

GPT:

Glutamate pyruvate transaminase

HDL:

High-density lipoprotein

HFD:

High-fat diet

iBAT:

Interscapular brown adipose tissue

LDL:

Low-density lipoprotein

PA:

Palmitic acid

PCOS:

Polycystic ovary syndrome

Prdm16 :

Positive regulatory domain containing 16

Pgc1α :

Peroxisome proliferator-activated receptor-gamma coactivator 1 alpha

PND:

Postnatal day

PPARγ:

Peroxisome proliferator-activated receptor gamma

pWAT:

Perirenal white adipose tissue

sWAT:

Inguinal subcutaneous white adipose tissue

Sirt1 :

Silent mating type information regulation 2 homolog-1

TG:

Triglycerides

T2DM:

Type 2 diabetes mellitus

T3:

Tri-iodothyronine

T4:

Prohormone tetraiodothyronine

UCP1:

Uncoupling protein 1

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Acknowledgements

This work was supported by grants to Xiao Luo from the National Natural Science Foundation of China (81871190 and 82270900) and Medical Basic-Clinical Integration Innovation Project from Xi'an Jiaotong University (YXJLRH2022014).

Funding

This work was supported by grants to Xiao Luo from the National Natural Science Foundation of China (81871190 and 82270900) and Medical Basic-Clinical Integration Innovation Project from Xi'an Jiaotong University (YXJLRH2022014).

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710061, China

    Zhao Yang, Guiying Yang, Miao Chen & Zhen Han

  2. Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, Xi’an, 710061, China

    Zhao Yang, Jianan Jiang, Yutian Tan, Guiying Yang, Jiaqi Huang, Jing Liu, Xiaojing Wei, Siyao Wang & Xiao Luo

  3. Institute of Neuroscience, Translational Medicine Institute, Xi’an Jiaotong University Health Science Center, Xi’an, 710061, China

    Zhao Yang, Jianan Jiang, Yutian Tan, Guiying Yang, Jiaqi Huang, Jing Liu, Xiaojing Wei, Siyao Wang & Xiao Luo

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  1. Zhao Yang
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Contributions

Conceptualization and design, L.X. and H.Z.; methodology and data acquisition, Y.Z., J. J-N., T. Y–T. and Y. G-Y.; interpretation of data, Y.Z., J. J-N., H. J-Q., L.J., C. M., T. Y–T., Y. G-Y. and W. S-Y; formal analysis, Y.Z., and W. X-J.; writing—original draft preparation, Y.Z.; writing-review and editing, Y.Z., L.X. and H.Z.; supervision, L.X. and H.Z.. All authors read and approved the manuscript.

L.X. and H.Z. are co-corresponding authors.

The authors declared that all data were generated in-house and that no paper mill was used.

Corresponding authors

Correspondence to Xiao Luo or Zhen Han.

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The authors declare that there are no dualities of interest with this study.

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Summary sentence

Maternal and post-weaning obesogenic diet induced the more adaptive alteration of thermogenesis and metrnl expression in female adult offspring, which may be one of the reasons why female offspring are more resistant to obesity and other metabolic related diseases.

Key Points

• The adaptive thermogenetic effects of maternal and perinatal HFD on iBAT and WAT metabolic phenotype were more evident in female offspring compared with male offspring.

• The expression of metrnl in three adipose depots and serum of adult offspring adaptively increased with significant sex- and depot-specificity.

• The correlation between serum metrnl level and fasting blood glucose, body weight and adipose mass weight showed significant sex-specificity.

• SiR-metrnl inhibited preadipocyte differentiation in sex-specific manner.

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Yang, Z., Jiang, J., Tan, Y. et al. Sexual dimorphism in thermogenic regulators and metrnl expression in adipose tissue of offspring mice exposed to maternal and postnatal overnutrition. J Physiol Biochem 80, 407–420 (2024). https://doi.org/10.1007/s13105-024-01013-2

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