Exocrine pancreas proteases regulate β-cell proliferation in zebrafish ciliopathy models and in murine systems

ABSTRACT Pancreatic β-cells are a critical cell type in the pathology of diabetes. Models of genetic syndromes featuring diabetes can provide novel mechanistic insights into regulation of β-cells in the context of disease. We previously examined β-cell mass in models of two ciliopathies, Alström Syndrome (AS) and Bardet-Biedl Syndrome (BBS), which are similar in the presence of metabolic phenotypes, including obesity, but exhibit strikingly different rates of diabetes. Zebrafish models of these disorders show deficient β-cells with diabetes in AS models and an increased β-cells absent diabetes in BBS models, indicating β-cell generation or maintenance that correlates with disease prevalence. Using transcriptome analyses, differential expression of several exocrine pancreas proteases with directionality that was consistent with β-cell numbers were identified. Based on these lines of evidence, we hypothesized that pancreatic proteases directly impact β-cells. In the present study, we examined this possibility and found that pancreatic protease genes contribute to proper maintenance of normal β-cell numbers, proliferation in larval zebrafish, and regulation of AS and BBS β-cell phenotypes. Our data suggest that these proteins can be taken up directly by cultured β-cells and ex vivo murine islets, inducing proliferation in both. Endogenous uptake of pancreatic proteases by β-cells was confirmed in vivo using transgenic zebrafish and in intact murine pancreata. Taken together, these findings support a novel proliferative signaling role for exocrine pancreas proteases through interaction with endocrine β-cells.

The Inclusion of the Microalga Scenedesmus sp. in Diets for Rainbow Trout, Onchorhynchus mykiss, Juveniles

A nutritional study was conducted to evaluate the inclusion of the green microalga Scenedesmus sp. at 5% (SCE-5) as an alternative fishmeal ingredient. This microalga was tested with four replicates during 45 days using isolipidic (18%), isoproteic (48%), and isoenergetic (1.9 MJ kg−1) diets. Fish fed Scenedesmus sp. showed similar growth and feed efficiency parameters as the control group. Regarding the digestive function, the SCE-5 diet enhanced the activity of alkaline pancreatic proteases, whereas it did not affect that of intestinal enzymes involved in nutrient absorption. No histological alterations were found in fish fed the SCE-5 diet, although a higher density of goblet cells in the anterior intestine and changes in gut microbiome diversity were found in this group, which collectively suggests positive effects of this green microalga on the intestine. Dietary Scenedesmus sp. improved the fillet’s nutritional quality in terms of n-3 polyunsaturated fatty acid (PUFA) levels, although it also increased its yellowish color. The overall results of this study showed that Scenedesmus sp. is a safe ingredient for compound feeds in rainbow trout when considering fish growth performance, animal condition, and health parameters, although it substantially affected the color of the fillet that may potentially affect consumers’ preferences.