High Fat Diet Dysregulates Hypothalamic-Pituitary Axis Gene Expression Levels which are Differentially Rescued by EPA and DHA Ethyl Esters

Abstract

Scope: Dietary fat composition can modulate gene expression in peripheral tissues in obesity. Observations of the dysregulation of growth hormone (GH) in obesity indicate that these effects extend to the hypothalamic-pituitary (H-P) axis. The authors thus determine whether specific high fat (HF) diets influence the levels of Gh and other key gene transcripts in the H-P axis.

Methods and results: C57BL/6 mice are fed a lean control diet or a HF diet in the absence or presence of OA, EPA, or DHA ethyl esters. Comparative studies are conducted with menhaden fish oil. The HF diet lowered pituitary Gh mRNA and protein levels, and cell culture studies reveal that elevated insulin and glucose can reduce Gh transcripts. Supplementation of the HF diet with OA, EPA, DHA, or menhaden fish oil do not improve pituitary Gh levels. The HF diet also impaired the levels of additional genes in the pituitary and hypothalamus, which are selectively rescued with EPA or DHA ethyl esters. The effects of EPA and DHA are more robust relative to fish oil.

Conclusion: A HF diet can affect H-P axis transcription, which can be mitigated in some genes by EPA and DHA, but not fish oil in most cases.

Keywords: growth hormone; hypothalamic-pituitary axis; n-3 PUFA; obesity.