Endocrine factors regulate food intake and growth, two interlinked physiological processes critical for the proper development of organisms. Somatic growth is mainly regulated by growth hormone (GH) and insulin-like growth factors I and II (IGF-I and IGF-II) that act on target tissues, including muscle, and bones. Peptidyl hormones produced from the brain and peripheral tissues regulate feeding to meet metabolic demands. The GH-IGF system and hormones regulating appetite are regulated by both internal (indicating the metabolic status of the organism) and external (environmental) signals. Among the external signals, the most notable are diet availability and diet composition. Macronutrients and micronutrients act on several hormone-producing tissues to regulate the synthesis and secretion of appetite-regulating hormones and hormones of the GH-IGF system, eventually modulating growth and food intake. A comprehensive understanding of how nutrients regulate hormones is essential to design diet formulations that better modulate endogenous factors for the benefit of aquaculture to increase yield. This review will discuss the current knowledge on nutritional regulation of hormones modulating growth and food intake in fish.

Nesfatin-1 is an 82 amino acid anorexigen encoded in a secreted precursor nucleobindin-2 (NUCB2). NUCB2 was named so due to its high sequence similarity with nucleobindin-1 (NUCB1). It was recently reported that NUCB1 encodes an insulinotropic nesfatin-1-like peptide (NLP) in mice. Here, we aimed to characterize NLP in fish. RT- qPCR showed NUCB1 expression in both central and peripheral tissues. Western blot analysis and/or fluorescence immunohistochemistry determined NUCB1/NLP in the brain, pituitary, testis, ovary and gut of goldfish. NUCB1 mRNA expression in goldfish pituitary and gut displayed a daily rhythmic pattern of expression. Pituitary NUCB1 mRNA expression was downregulated by estradiol, while testosterone upregulated its expression in female goldfish brain. High carbohydrate and fat suppressed NUCB1 mRNA expression in the brain and gut. Intraperitoneal injection of synthetic rat NLP and goldfish NLP at 10 and 100 ng/g body weight doses caused potent inhibition of food intake in goldfish. NLP injection also downregulated the expression of mRNAs encoding orexigens, preproghrelin and orexin-A, and upregulated anorexigen cocaine and amphetamine regulated transcript mRNA in goldfish brain. Collectively, these results provide the first set of results supporting the anorectic action of NLP, and the regulation of tissue specific expression of goldfish NUCB1.

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Myeloproliferative neoplasms (MPN) are uncommon in children/young adults. Here we present data on unselected patients diagnosed before 25 years of age included from 38 centres in 15 countries. Sequential patients were included. We identified 444 patients, with median follow up 9.7 years (0-47.8). Forty-nine (11.1%) had a history of thrombosis at diagnosis, 49 new thrombotic events were recorded (1.16 % pt/year), peri-hepatic vein thromboses were most frequent (47.6% venous events) and logistic regression identified JAK2V617F mutation (p=0.016) and hyperviscosity symptoms (visual disturbances, dizziness, vertigo, headache) as risk factors (p=0.040). New hemorrhagic events occurred in 44 patients (9.9%, 1.04 % pt/y). Disease transformation occurred in 48 patients (10.9%, 1.13 % pt/year), usually to myelofibrosis (7.5%) with splenomegaly as a novel risk factor for transformation in ET (p= 0.000) in logistical regression. Eight deaths (1.8%) were recorded, three after allogeneic stem cell transplantation. Concerning conventional risk scores: IPSET-T and IPSET-NT differentiated ET patients in terms of thrombotic risk. Both scores identified high-risk patients with the same median thrombosis-free survival of 28.5y. No contemporary scores were able to predict survival for young ET or PV patients. Our data represents the largest real-world study of MPN patients age <25 years at diagnosis). Rates of thrombotic events and transformation were higher than expected compared with the previous literature. Our study provides new and reliable information as a basis for prospective studies, trials, and development of harmonized international guidelines for the specific management of young patients with MPN.