GLP-1R/NPY2R regulate gene expression, ovarian and adrenal morphology in HFD mice

Area of Science:

• Endocrinology
• Reproductive Biology
• Metabolic Research

Background:

• Glucagon-like peptide-1 receptor (GLP-1R) and neuropeptide Y receptors (NPYRs) are present in reproductive tissues and influence gonadal function.
• High-fat diet (HFD) can disrupt metabolic and reproductive health.

Purpose of the Study:

• To investigate the effects of exendin-4 (Ex-4) and peptide YY (PYY) (3-36) on the endocrine ovaries and adrenals of HFD-induced obese mice.
• To explore the potential of modulating GLP-1R and NPY2R for improving female reproductive physiology.

Main Methods:

• Mice were fed a high-fat diet (HFD) and treated with exendin-4 (Ex-4) or peptide YY (PYY) (3-36).
• Evaluated estrous cycle, hormone levels (luteinizing hormone), adrenal morphology (capsule and zona glomerulosa thickness), ovarian follicle counts, and corpora lutea.
• Analyzed gene expression in adrenal and ovarian tissues.

Main Results:

• Ex-4 and PYY (3-36) reduced blood glucose and energy intake but did not affect body weight.
• Ex-4 normalized the estrous cycle disrupted by HFD and increased corpora lutea.
• Peptide treatments reversed HFD-induced adrenal cortex thinning and increased follicle health in ovaries.
• Hormone levels and gene expression related to reproductive function were modulated by peptide treatments.

Conclusions:

• Modulation of GLP-1R and NPY2R by Ex-4 and PYY (3-36) positively impacts female reproductive physiology in HFD mice.
• These peptides demonstrate a direct effect on ovarian and adrenal function, offering potential therapeutic avenues for metabolic and reproductive disorders.