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Maternal betaine protects rat offspring from glucocorticoid-induced activation of lipolytic genes in adipose tissue through modification of DNA methylation

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Abstract

Purpose

Excessive exposure of glucocorticoids activates adipose lipolysis, increases circulating free fatty acids, and contributes to ectopic lipid deposition in liver and skeletal muscle. Our previous study demonstrated that maternal betaine supplementation attenuates glucocorticoid-induced hepatic lipid accumulation in rat offspring. However, it is unclear whether maternal betaine supplementation is effective in preventing glucocorticoid-induced lipolysis in the adipose tissue of offspring.

Methods

In this study, 20 pregnant rats were fed with basal or betaine-supplemented (10 g/kg) diets throughout gestation and lactation, and the offspring rats were raised on the basal diet from weaning till 3 months of age followed by daily intraperitoneal injection of saline or 0.1 mg/kg dexamethasone (DEX) for 3 weeks.

Results

Chronic DEX treatment significantly (P < 0.05) decreased serum corticosterone level and increased proinflammatory cytokines, such as TNFα, IL-1β, and IL-6. Meanwhile, GR protein content in adipose tissue was increased in response to DEX treatment, which was associated with a significant (P < 0.05) up-regulation of ATGL and HSL expression at both mRNA and protein levels. All these DEX-induced changes were significantly (P < 0.05) attenuated in progeny rats derived from betaine-supplemented dams. Furthermore, DEX-induced hypomethylation of ATGL and HSL gene promoters was reversed by maternal betaine supplementation.

Conclusions

Taken together, these results suggest that maternal betaine supplementation is effective in alleviating glucocorticoid-induced lipolysis in adipose tissue with modification of DNA methylation on the promoter of lipolytic genes.

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Abbreviations

ACC:

Acetyl-CoA carboxylase

AKT:

Serine/threonine-specific protein kinase

AMPK:

AMP-activated protein kinase

ATGL:

Adipose triglyceride lipase

FAS:

Fatty acid synthase

GR:

Glucocorticoid receptor

HSL:

Hormone sensitive lipase

IL-1β:

Interleukin 1β

IL-6:

Interleukin 6

NAFLD:

Non-alcoholic fatty liver disease

TNFα:

Tumor necrosis factor α

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Acknowledgements

The present study was supported by the National Key Research and Development Program of China (2016YFD0500502), the National Basic Research Program of China (2012CB124703), the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD), and Jiangsu Collaborative Innovation Center of Meat Production and Processing, Quality and Safety Control.

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Authors and Affiliations

  1. MOE Joint International Research Laboratory of Animal Health and Food Safety, Nanjing Agricultural University, Nanjing, 210095, People’s Republic of China

    Nannan Zhao, Shu Yang, Bo Sun, Yue Feng & Ruqian Zhao

  2. Key Laboratory of Animal Physiology and Biochemistry, Nanjing Agricultural University, Nanjing, 210095, People’s Republic of China

    Nannan Zhao, Shu Yang, Bo Sun, Yue Feng & Ruqian Zhao

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  1. Nannan Zhao
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  2. Shu Yang
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  3. Bo Sun
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Contributions

NZ contributed to hormone and gene assays, data analysis, and drafting of the manuscript. SY was responsible for animal care, breeding and sampling. BS and YF provided technical support. RZ contributed to conception, experimental design, data interpretation, and critical revision of the manuscript.

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Correspondence to Ruqian Zhao.

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Zhao, N., Yang, S., Sun, B. et al. Maternal betaine protects rat offspring from glucocorticoid-induced activation of lipolytic genes in adipose tissue through modification of DNA methylation. Eur J Nutr 59, 1707–1716 (2020). https://doi.org/10.1007/s00394-019-02025-1

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