Dexamethasone Rescues an Acute High-Fat Diet-Induced Decrease in Human Growth Hormone Gene Expression in Male...

Area of Science:

• Endocrinology
• Molecular Biology
• Metabolic Research

Background:

• Obesity during puberty exacerbates insulin resistance and increases type 2 diabetes risk.
• Pubertal human growth hormone (hGH) is crucial for growth and pancreatic beta-cell maintenance.
• Overeating and obesity negatively impact hGH production, particularly during the light phase, linked to reduced Bmal1.

Purpose of the Study:

• To investigate if glucocorticoids (GCs) can counteract the suppressive effects of a high-fat diet (HFD) on hGH gene expression in pubescent mice.
• To determine if dexamethasone (DEX) administration can mitigate HFD-induced decreases in hGH production and restore Bmal1 levels.

Main Methods:

• Male transgenic mice carrying the human growth hormone gene (171hGH/CS) were fed a high-fat diet (HFD) for 3 days.
• Mice received daily injections of dexamethasone (DEX) during either the light or dark phase.
• hGH gene (hGH-N) expression, Bmal1 transcript levels, and serum corticosterone were measured at various time points post-treatment.

Main Results:

• Dexamethasone (DEX) treatment significantly increased or rescued hGH-N RNA levels, counteracting HFD effects.
• DEX administration was associated with elevated Bmal1 transcripts, even when endogenous corticosterone was suppressed.
• A diet-dependent effect on hGH-N RNA was observed 36 hours post-treatment, primarily in the light phase, suggesting residual DEX effects.

Conclusions:

• This study provides the first in vivo evidence that glucocorticoids (GCs) directly influence human growth hormone (hGH) gene expression.
• GCs, administered as DEX, can limit the negative impact of overeating and obesity on hGH production during puberty.
• Targeting GCs may offer a therapeutic approach to manage endocrine disruptions associated with obesity in adolescents.