Hyperandrogenism in POMCa-deficient zebrafish enhances somatic growth without increasing adiposity

The endocrine regulatory roles of the hypothalamic-pituitary-adrenocortical axis on anxiety-like behavior and metabolic status have been found throughout animal taxa.However,the precise effects of the balancing adrenal corticosteroid biosynthesis under the influence of adrenocorticotrophic hormone(ACTH),a pro-opiomelanocortin(POMC)-derived peptide,on animal energy expenditure and somatic growth remain unknown.POMC has also been identified as one of the candidate loci for polycystic ovary syndrome,which features hyperandrogenism and some prevalence of obesity in patients.Here we show that zebrafish lacking functional POMCa exhibit similar phenotypes of stress response and body weight gain but not obesity as observed in mammalian models.In contrast with the impaired anorexigenic signaling cascade of melanocyte-stimulating hormones and leptin,which are responsible for their obesity-prone weight gain observed in various pome mutant mammals,analyses with our pomca mutant series indicate that ACTH is the key regulator for the phenotype with enhanced somatic growth without obesity in pomca-deficient zebrafish.Hypocortisolism associated with hyperandrogenism has been observed in the pomca-deficient zebrafish,with enhanced activation of mammalian target of rapamycin complex 1;reutilization of amino acids and fatty acid^-oxidation are observed in the muscle tissue of the pomca-deficient fish.After reducing hyperandrogenism by crossing our pomca mutant fish with a cy p l 7a 1-deficient background,the phenotype of enhanced somatic growth in pomca-deficient fish was no longer observed.Thus,our work also demonstrated that the role of POMCa in stress response seems to be conserved in vertebrates,whereas its effect on adipostasis is unique to teleosts.

饥饿对幼年斑马鱼下丘脑摄食相关性神经肽表达的影响

脊椎动物下丘脑中的神经肽Y(Neuropeptide Y,NPY)、GALANIN和GMAP蛋白前体(GALANIN and GMAP prepropeptide,GAL)、Agouti相关蛋白(Agouti related neuropeptide,AGRP)和阿片促黑色素原(Proopiomelanocortin,POMC)与摄食密切相关,但在斑马鱼中对这些神经肽与摄食之间关系的研究较少。本文通过原位杂交技术和实时定量PCR方法,观察饥饿1 d、饥饿2 d和饥饿2 d喂食2 d后斑马鱼下丘脑中npy、galanin、agrp和pomca的表达情况。结果显示,饥饿处理之后,agrp和galanin在斑马鱼下丘脑中的表达量显著上升(P<0.05)。与对照组相比,饥饿2 d后斑马鱼下丘脑中pomca表达量显著下降(P<0.05)。饥饿2 d喂食2 d后斑马鱼下丘脑中pomca、agrp和galanin的表达量与对照组相比没有显著性差异。所有实验中npy在斑马鱼下丘脑中的表达没有显著性差异。这表明饥饿处理促使斑马鱼下丘脑中agrp和galanin表达上调,pomca表达下调;及时摄食可以恢复agrp、galanin和pomca在下丘脑中的表达水平。