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.

Growth hormone (GH), mainly produced from the pituitary somatotrophs is a key endocrine regulator of somatic growth. GH, a pleiotropic hormone, is also involved in regulating vital processes, including nutrition, reproduction, physical activity, neuroprotection, immunity, and osmotic pressure in vertebrates. The dysregulation of the pituitary GH and hepatic insulin-like growth factors (IGFs) affects many cellular processes associated with growth promotion, including protein synthesis, cell proliferation and metabolism, leading to growth disorders. The metabolic and growth effects of GH have interesting applications in different fields, including the livestock industry and aquaculture. The latest discoveries on new regulators of pituitary GH synthesis and secretion deserve our attention. These novel regulators include the stimulators adropin, klotho, and the fibroblast growth factors, as well as the inhibitors, nucleobindin-encoded peptides (nesfatin-1 and nesfatin-1–like peptide) and irisin. This review aims for a comparative analysis of our current understanding of the endocrine regulation of GH from the pituitary of vertebrates. In addition, we will consider useful pharmacological molecules (i.e. stimulators and inhibitors of the GH signaling pathways) that are important in studying GH and somatotroph biology. The main goal of this review is to provide an overview and update on GH regulators in 2020. While an extensive review of each of the GH regulators and an in-depth analysis of specifics are beyond its scope, we have compiled information on the main endogenous and pharmacological regulators to facilitate an easy access. Overall, this review aims to serve as a resource on GH endocrinology for a beginner to intermediate level knowledge seeker on this topic.

Nesfatin-1, the N-terminal fragment of nucleobindin 2 (NUCB2), is an 82 amino-acid peptide that inhibits food intake and exerts weight-reducing effects. Nesfatin-1 has been proposed as a potential anti-obesity peptide. However, studies to date have mainly focused solely on the acute satiety effects of centrally administered nesfatin-1. The main objective of our studies was to characterize the long-term/chronic effects of peripheral administration of nesfatin-1 on whole-body energy balance and metabolic partitioning in male Fischer 344 rats. Short-term (1 day) subcutaneous infusion of nesfatin-1 (50 µg/kg body weight/day) using osmotic mini-pumps increased spontaneous physical activity and whole-body fat oxidation during the dark phase. This was accompanied by decreased food intake and basal metabolic rate compared to saline infused controls. On the seventh day of nesfatin-1 infusion, cumulative food intake and total spontaneous physical activity during the dark phase were significantly reduced and elevated, respectively. Meanwhile, intraperitoneal injection of nesfatin-1 only caused a dark phase specific reduction in food intake and an increase in physical activity. NUCB2 mRNA expression in the brain and stomach, as well as serum NUCB2 concentrations were significantly reduced after 24 h fasting, while a post-prandial increase in serum NUCB2 was found in ad libitum fed rats. Collectively, our results indicate that chronic peripheral administration of nesfatin-1 at the dose tested, results in a sustained reduction in food intake and modulation of whole body energy homeostasis.

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.