Paternal Obesity's Genetic Impact on Offspring Metabolism Revealed in NTU Study

Taipei – A groundbreaking study from National Taiwan University (NTU) reveals that a father's obesity can have a significant, transgenerational impact on his offspring's metabolic health. The research, published in the international journal Nature Communications, demonstrates that paternal obesity can influence the next generation's metabolic function through epigenetic modifications in sperm.

Globally, obesity is a growing concern, with over a billion people classified as obese by the World Health Organization. While previous research has largely focused on the mother's physiological state affecting embryonic development, this new study shifts focus to the father's role. Assistant Professor Huang Chien from NTU's Department of Animal Science and Technology led the team that investigated the "let-7-DICER axis" in male obesity, providing the first concrete evidence that paternal obesity can impair offspring's metabolic and fat tissue health.

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male obesity through the let-7-DICER axis leads to first-generation offspring's adipose mitochondrial dysfunction

Using mouse models, the researchers observed that offspring fathered by obese male mice exhibited significantly reduced expression of genes related to the mitochondrial respiratory chain in their white adipose tissue. This led to metabolic dysfunction, mirroring characteristics of the obese fathers. Further experiments involving the direct microinjection of let-7, simulating obese sperm, into healthy fertilized eggs confirmed this effect. The resulting mice, even when fed a normal diet, showed impaired glucose tolerance and damaged mitochondrial-related genes in their fat tissue, replicating the paternal obesity's inherited traits.

The study also analyzed human sperm samples. Results indicated that after men successfully lost weight through lifestyle changes, the expression of hsa-let-7 in their sperm decreased. This suggests that let-7 plays a crucial role in the epigenetic makeup of human gametes and embryonic development. The NTU team's findings challenge traditional notions of inheritance, showing how environmental factors like diet and weight can embed "metabolic memory" into the epigenetic code of sperm. This research opens new avenues for preventing metabolic syndrome across generations and underscores the critical importance of paternal health prior to conception.

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metabolic memory