Paternal Nicotine Exposure Linked to Sex-Specific Metabolic Changes in Offspring

Mouse study finds fathers' nicotine use may increase diabetes risk in children

Mar. 27, 2026 at 7:51am

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A study in mice found that paternal nicotine exposure was associated with sex-specific metabolic changes in offspring. Female offspring had lower fasting glucose and insulin levels with enhanced adipose insulin signaling, while male offspring had lower insulin and glucagon levels along with altered liver transcriptional profiles, suggesting paternal tobacco use could increase the risk for diabetes in descendants.

Why it matters

Rising rates of metabolic diseases have spurred research into environmental factors like nicotine exposure that can have multigenerational effects. While most studies have focused on maternal exposure, this study highlights the potential impact of paternal nicotine use, which is more prevalent, on offspring metabolism and disease risk.

The details

Researchers randomly assigned 3-week-old male mice to receive nicotine or a control in drinking water for 6 weeks, then mated them with unexposed females. The 8-week-old offspring underwent glucose and insulin tolerance tests, as well as analysis of plasma hormone levels and liver/adipose tissue transcriptomes. Female offspring of nicotine-exposed fathers had lower fasting glucose and insulin, with enhanced insulin signaling in adipose tissue. Male offspring had reduced plasma glucagon and insulin, with liver gene expression changes indicating impaired fasting adaptation and increased susceptibility to insulin resistance and type 2 diabetes.

  • Mice were treated with nicotine or control for 6 weeks starting at 3 weeks of age.
  • Offspring were assessed at 6-8 weeks of age.

The players

Stephanie Aguiar

Lead author of the study, from the Department of Microbiology and Environmental Toxicology at the University of California, Santa Cruz.

Raquel Chamorro-Garcia

Corresponding author of the study and recipient of University of California Santa Cruz Start-up Funds.

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What they’re saying

“Considering the evidence that male exposure can increase the likelihood of their children developing chronic diseases, it is crucial to incorporate male health into preconception care.”

— Raquel Chamorro-Garcia

What’s next

The researchers plan to further investigate the mechanisms behind the sex-specific metabolic changes observed, as well as assess the long-term disease risks in the offspring.

The takeaway

This study highlights the importance of considering paternal health factors, like nicotine exposure, when addressing the rising rates of metabolic diseases across generations. Incorporating male preconception health into clinical care could help mitigate the potential intergenerational impacts.