In a fish study, giving the brain DHA, EPA, or linoleic acid changed the activity of a fatty‑acid sensor (CD36) and a hormone‑regulating protein (PPARα). This, in turn, altered the levels of the fish's own GnRH genes, which control reproduction. Blocking the sensor or the PPARα pathway reduced these effects, showing the fatty acids act through that route.

The binding of fatty acid (FA) to fatty acid translocase (FAT/CD36) and subsequent regulation of lipid metabolism transcription factors, such as peroxisome proliferator-activated receptors α (PPARα) and sterol regulatory element-binding protein-1c (SREBP-1c), is an important hypothalamic fatty acid-sensing mechanism in vertebrates. The hypothalamus exhibits responsiveness to specific fatty acids and is involved in reproductive regulation. However, the link between FA sensing and reproductive regulation in the hypothalamus remains poorly understood teleosts. Therefore, the expression of genes involved in the FA-sensing mechanism-such as fat/cd36, pparα, and srebp1c, as well as gonadotropin-releasing hormone (GnRH: cgnrh, sgnrh, sbgnrh) in the hypothalamus-was investigated after intracranial administration and hypothalamic incubation of polyunsaturated fatty acids (PUFAs), including docosahexaenoic acid (DHA), eicosapentanoic acid (EPA), and linoleic acid (LA) for 4 h in the spotted scat (Scatophagus argus). Compared to the control, intracranial administration and hypothalamic incubation of DHA and LA, as well as hypothalamic incubation of EPA, increased the levels of fat/cd36, pparα, and srebp1c. However, the expression of fat/cd36 and pparα was significantly decreased, and the level of srebp1c showed a downward trend only in the EPA group when co-incubated with the FAT/CD36 inhibitor Sulfo-N-succinimidyl oleate sodium (SSO), compared to incubation with EPA alone. After the application of PPARα antagonist GW6471, the expression of pparα in the hypothalamus decreased significantly in the DHA, EPA, and LA treatment groups, compared to incubation with DHA, EPA, and LA alone. Levels of fsh and lh in the pituitary gland were changed significantly after the intracranial administration of DHA, EPA, and LA. Compared to the control, the levels of cgnrh, sgnrh, and sbgnrh increased in the hypothalamus after both hypothalamic incubation and intracranial administration of EPA and LA. Levels of cgnrh increased in the hypothalamus after incubation, but not after intracranial administration of DHA. However, compared to the control, levels of sgnrh and sbgnrh increased after hypothalamic incubation with DHA and EPA. Only sgnrh levels decreased after incubation with LA in the presence of SSO compared to the FA treatment group alone. In the presence of GW6471, only sgnrh levels decreased after incubation with LA in the presence of SSO compared to the FA treatment group alone; the levels of cgnrh, sgnrh, and sbgnrh after LA incubation, the levels of sbgnrh after EPA incubation, and the levels of sbgnrh after DHA incubation were all significantly decreased compared to the control. These results showed that DHA, EPA, and LA could activate fat/cd36 and pparα, which are involved in reproductive regulation in the hypothalamus of the spotted scat. These results provide evidence that hypothalamic FA sensing is involved in regulating reproduction in teleosts.