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

  • Nannan Zhao
  • Shu Yang
  • Bo Sun
  • Yue Feng
  • Ruqian ZhaoEmail author
Original Contribution



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.


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.


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.


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.


Maternal Betaine Glucocorticoid Lipolysis DNA methylation 



Acetyl-CoA carboxylase


Serine/threonine-specific protein kinase


AMP-activated protein kinase


Adipose triglyceride lipase


Fatty acid synthase


Glucocorticoid receptor


Hormone sensitive lipase


Interleukin 1β


Interleukin 6


Non-alcoholic fatty liver disease


Tumor necrosis factor α



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.

Author 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.

Compliance with ethical standards

Conflict of interest

The authors declare that there is no conflict of interest associated with this manuscript.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.MOE Joint International Research Laboratory of Animal Health and Food SafetyNanjing Agricultural UniversityNanjingPeople’s Republic of China
  2. 2.Key Laboratory of Animal Physiology and BiochemistryNanjing Agricultural UniversityNanjingPeople’s Republic of China

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