GLP-1 Drug Liraglutide Protects Testosterone-Producing Cells by Boosting Mitochondrial Function | Research

The takeaway

Liraglutide improved mitochondrial performance and reduced oxidative stress in mouse Leydig cells (the testicular cells that produce testosterone), suggesting a potential protective effect on male reproductive function.

Enhanced mitochondrial respiration across multiple measures
Pharmacological-dose liraglutide increased basal respiration, maximal respiration, and ATP-linked oxygen consumption in Leydig cells while reducing harmful reactive oxygen species

What the researchers found

Liraglutide at pharmacological concentrations increased the metabolic viability of mouse Leydig cells and reduced reactive oxygen species (ROS) production at all concentrations tested. Mitochondrial performance was significantly enhanced: increased basal respiration, maximal respiration, proton leak, and ATP-linked oxygen consumption rate. Mitochondrial membrane potential and mtDNA copy number were also assessed. Androstenedione (testosterone precursor) production was unchanged, likely due to inherent limitations of the BLTK1 cell line in supporting full steroidogenesis.

Why it matters

Obesity and type 2 diabetes are strongly associated with low testosterone and male infertility. As GLP-1 receptor agonists become the dominant treatment for these conditions, understanding their effects on reproductive cells is crucial. This study provides the first evidence that liraglutide directly benefits Leydig cell mitochondrial function, potentially explaining clinical observations of improved testosterone levels in men taking GLP-1 drugs for weight loss.

The numbers in context

Increased metabolic viability · Reduced ROS at all concentrations · Enhanced basal respiration, maximal respiration, proton leak, ATP-linked OCR · Androstenedione production unchanged

How the study worked

In vitro study using the BLTK1 mouse Leydig cell line. Cells were cultured with or without liraglutide at pharmacological and supra-pharmacological concentrations. Assessed: metabolic viability, cell proliferation, LDH release (cytotoxicity), ROS production, mitochondrial membrane potential, real-time mitochondrial respiration (Seahorse-style analysis), mtDNA copy number, and androstenedione production.

Who was studied

In vitro study using BLTK1 mouse Leydig cell line treated with liraglutide at pharmacological and supra-pharmacological concentrations

What this study cannot tell us

This is an in vitro study using an immortalized mouse cell line (BLTK1), which may not fully represent primary Leydig cells or human testicular physiology. The lack of change in androstenedione production may reflect cell line limitations rather than a true null effect on steroidogenesis. No in vivo validation was performed. The concentrations used may not perfectly reflect what Leydig cells encounter in the testis during systemic liraglutide treatment.

How to read the evidence

This is a preliminary in vitro study using an immortalized mouse cell line. While the mitochondrial findings are clearly demonstrated, the translational relevance to human male reproductive health requires validation in primary cells and in vivo models.

When this study was published

Published in 2025, this study addresses a timely question as GLP-1 agonists are increasingly prescribed to millions of men of reproductive age for obesity and diabetes management.

The bigger picture

The relationship between metabolic drugs and male reproductive health is increasingly recognized as clinically important. Millions of men taking GLP-1 agonists for diabetes and obesity may experience changes in testosterone and fertility. Understanding whether these effects are positive (improved testicular function through reduced oxidative stress) or negative is essential for clinical counseling. This study adds mechanistic evidence suggesting the effects may be protective.

Questions still open

Would liraglutide's protective effects on Leydig cell mitochondria translate to improved testosterone levels in men taking the drug?
Do other GLP-1 receptor agonists like semaglutide have similar effects on Leydig cell function?
Could the mitochondrial benefits observed in vitro be replicated in primary Leydig cells or in vivo animal models with metabolic dysfunction?

Common questions

What are Leydig cells and why do they matter for male health?

Leydig cells are found in the testicles and are responsible for producing testosterone — the primary male sex hormone. Testosterone is essential for fertility, muscle mass, bone density, mood, and sexual function. When Leydig cells are damaged by metabolic stress (from obesity or diabetes), testosterone production drops, contributing to infertility, low energy, and other health problems.

Could GLP-1 drugs like Ozempic or Mounjaro affect male fertility?

This is an active area of research. This study suggests that liraglutide (a GLP-1 drug related to semaglutide/Ozempic) may actually protect the cells that produce testosterone by improving their energy production and reducing oxidative damage. However, this was only shown in lab-grown cells, not in men. Some clinical studies have noted improved testosterone levels in men who lose weight on GLP-1 drugs, but it's unclear if that's from weight loss or direct drug effects.

Read the original research

A Pharmacological Dose of Liraglutide Improves Mitochondrial Performance in Mouse Leydig Cells.

International journal of molecular sciences, 26(18)

View on PubMed ↗Publisher’s paper ↗

Citation

Oliveira-Lopes, Bruno; Braga, Patrícia C; Oliveira, Pedro F; Alves, Marco G; Bernardino, Raquel L. (2025). A Pharmacological Dose of Liraglutide Improves Mitochondrial Performance in Mouse Leydig Cells.. International journal of molecular sciences, 26(18). https://doi.org/10.3390/ijms26188903