CRISPR/Cas9-mediated pomc knockout in Nile tilapia enhances growth performance through feeding and IGF1 regulation

Proopiomelanocortin (POMC) is a neuroendocrine precursor critical for regulating energy homeostasis and feeding behavior across vertebrates. Although POMC deficiency causes hyperphagia and increased body weight in model organisms including mice and zebrafish, there have been no reports of pomc knockout in commercially farmed fishes to date. This study presents a systematic investigation of pomc knockout in one of the most widely farmed fish, Nile tilapia ( Oreochromis niloticus ), revealing its dual role in enhancing growth performance through appetite stimulation and endocrine regulation. Compared to wild type fish, pomc −/− fish exhibited 33 % higher feed intake, 65 % greater body weight, and 20 % improved feed conversion ratio (FCR) under full feeding conditions at 150 days post fertilization. Remarkably, even when fed to match wild-type food intake, pomc −/− mutants showed 18 % greater body weight and 15 % improved FCR. Transcriptomic profiling and ELISA demonstrated that POMC deficiency elevated the IGF1 signaling pathway, in line with reduced hepatic lipid storage and accelerated myocyte proliferation in pomc −/− fish found by histological analyses. These results revealed that disruption of pomc prevented obesity and promoted growth. Meanwhile, pomc −/− tilapia exhibited significantly higher levels of crude ash and crude protein, along with reduced crude fat levels in muscle. The increased levels of essential amino acids and flavor amino acids suggest that pomc −/− tilapia may possess superior nutritional value and umami taste. The pomc −/− fish showed reduced polyunsaturated fatty acids (PUFAs), but exhibited unchanged levels of key PUFAs with significant health benefits including EPA and DHA. In summary, pomc disruption represents a promising genetic approach for enhancing growth performance and feed efficiency in Nile tilapia, underscoring its potential as a valuable target in selective breeding programs for aquaculture improvement. • Disruption of POMC in tilapia induces hyperphagia, enhancing growth feed efficiency. • POMC deficiency elevates the IGF1 signaling pathway, reducing hepatic lipid storage and accelerating myocyte proliferation. • POMC knockout yields fast-growing tilapia exhibiting improved muscle protein retention and reduced fat deposition.