CHOP is dispensable for exercise-induced increases in GDF15

Area of Science:

• Cellular Biology
• Endocrinology
• Exercise Physiology

Background:

• Growth Differentiation Factor 15 (GDF15) is a secreted hormone and a marker of cellular stress.
• CHOP (C/EBP homologous protein) is a key transcriptional regulator of GDF15 and an endoplasmic reticulum stress protein.
• Exercise is known to increase GDF15 levels, but the regulatory mechanisms are unclear.

Purpose of the Study:

• To investigate whether CHOP regulates GDF15 expression and secretion during exercise.
• To explore the relationship between ER stress, obesity, and exercise-induced GDF15.

Main Methods:

• Examined circulating GDF15 and tissue GDF15 mRNA expression in response to acute exercise.
• Utilized lean, obese, trained, sedentary, and CHOP-deficient mouse models.
• Assessed markers of endoplasmic reticulum stress.

Main Results:

• Obesity augmented exercise-induced GDF15, despite similar ER stress markers in lean and obese mice.
• Exercise-induced GDF15 increased similarly in trained and sedentary mice at the same relative intensity.
• Exercise-induced GDF15 increases were preserved in CHOP-deficient mice.

Conclusions:

• Exercise-induced GDF15 expression and secretion are independent of ER stress and CHOP.
• The findings suggest alternative pathways mediate GDF15 regulation during physical activity.