Hypothalamic neurosecretory protein GM causes fat deposition and suppresses gonadal maturation in Japanese quail

Introduction: Central regulation of energy homeostasis is essential for balancing lipid storage and reproductive investment; however, the hypothalamic factors governing this trade-off remain incompletely defined in birds. Neurosecretory protein GM (NPGM), an 83-amino acid hypothalamic factor, was investigated for its role in energy allocation during sexual maturation in Japanese quail (Coturnix japonica). Methods: Male and female quails at the onset of sexual maturation received chronic intracerebroventricular administration of NPGM for 13 days via osmotic pumps, during which their body mass, food intake, and water intake were monitored daily. At the endpoint, peripheral tissue and muscle masses, serum metabolite levels (glucose, fatty acids, triglycerides, testosterone, and 17{beta}-estradiol), hepatic triglyceride content, and gene expression profiles of hypothalamic feeding/reproductive genes and hepatic/adipose lipid metabolic genes were evaluated. Results: NPGM increased subcutaneous and abdominal fat in both sexes and was associated with suppressed gonadal maturation, as indicated by reduced testicular mass relative to body mass and lower testosterone levels in males, as well as a trend toward reduced ovarian mass and lower 17{beta}-estradiol levels in females. Sex-dependent metabolic phenotypes emerged: males exhibited increased body mass gain, hyperphagia, elevated water intake, enlarged liver, pancreas, and heart, higher serum and hepatic triglyceride levels, increased hepatic SCD1 expression, and reduced hepatic CGI-58, PPAR{gamma}, SLC2A2, and CD36. In contrast, females showed fat accumulation without hyperphagia or hepatic triglyceride elevation, accompanied by reduced hepatic VTG2 and APOV1 and decreased adipose ATGL, LPL, and FATP. Hypothalamic AGRP expression decreased in males, whereas both NPY and AGRP decreased in females. Discussion: These findings demonstrate that central NPGM shifts energy allocation from reproduction toward lipid storage through sex-dependent endocrine and metabolic mechanisms, identifying NPGM as a neuroendocrine regulator of energy allocation during sexual maturation in Japanese quails.