AgRP neurons shape the sperm small RNA payload.

Paternal dietary patterns and obesity can affect offspring through epigenetic signals in sperm RNA. By activating hypothalamic Agouti-related peptide (AgRP) neurons in mice to simulate obesity's effects, we observed changes in the small noncoding RNA payload of sperm. These alterations, particularly in transfer RNA-derived small RNAs (tsRNAs), are similar to those induced by short-term high-fat diets, suggesting a common upstream regulatory mechanism involving AgRP neurons that affects metabolic epigenetic inheritance.