Chemical chaperones reduce ER stress and restore glucose homeostasis in a mouse model of type 2 diabetes

Endoplasmic reticulum (ER) stress is a key link between obesity, insulin resistance, and type 2 diabetes. Here, we provide evidence that this mechanistic link can be exploited for therapeutic purposes with orally active chemical chaperones. 4-Phenyl butyric acid and taurine-conjugated ursodeoxycholic acid alleviated ER stress in cells and whole animals. Treatment of obese and diabetic mice with these compounds resulted in normalization of hyperglycemia, restoration of systemic insulin sensitivity, resolution of fatty liver disease, and enhancement of insulin action in liver, muscle, and adipose tissues. Our results demonstrate that chemical chaperones enhance the adaptive capacity of the ER and act as potent antidiabetic modalities with potential application in the treatment of type 2 diabetes.     

Chimeric mice with humanized liver as a model for testing organophosphate and carbamate pesticide exposure

BACKGROUND

Diagnosis of acute intoxication with organophosphate (OP) or carbamate (CM) pesticides in humans is achieved by measuring plasma butyrylcholinesterase (BuChE) activity. However, BuChE activity is not an ideal biomarker in experimental animal models. The aim of this study was to establish an experimental mouse model for evaluating exposure to OP and CM pesticides by monitoring BuChE activity using chimeric mice in which the liver was reconstituted with human hepatocytes.

RESULTS

A single oral administration of acephate (300 mg/kg), chlorpyrifos (10 mg/kg), fenobucarb (300 mg/kg) or molinate (250 mg/kg) in chimeric mice led to inhibition of >95%, > 95%, 28% and 60% of plasma BuChE activity after 7, 0.5, 0.5 and 7 h, respectively. Dose‐dependent decreases in plasma BuChE activity were also observed for acephate and chlorpyrifos. A 5‐day repeated‐dose study with 10 or 30 mg/kg acephate found a constitutive reduction in plasma BuChE activity to 80% and 70% of pre‐dose levels, respectively.

CONCLUSION

Changes in plasma BuChE activity in chimeric mice with humanized liver clearly reflected the exposure levels of OP and CM pesticides. These results suggest that the humanized‐liver mouse model may be suitable for estimating levels of exposure to these pesticides in humans. © 2017 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.     

Effect of shelter acclimation on the post-release survival of hatchery-reared black-spot tuskfish <Emphasis Type="Italic">Choerodon schoenleinii</Emphasis>: laboratory experiments using the reef-resident predator white-streaked grouper <Emphasis Type="Italic">Epinephelus ongus</Emphasis>

A critical component of many releasing projects is the identification and subsequent implementation of optimal release strategies that can decrease post-release predation mortalities. We performed laboratory experiments to investigate whether acclimation to shelters affects the post-release survival of hatchery-reared black-spot tuskfish Choerodon schoenleinii in the presence of a reef-resident predator, the white-streaked grouper Epinephelus ongus. Tuskfish were exposed to groupers under three different experimental conditions/treatments: (1) acclimation of fish to shelters prior to their exposure to groupers; (2) no acclimation of fish to shelters, but with shelters available during their exposure to groupers; (3) fish not acclimated to shelters and no shelters available during their exposure to groupers. Tuskfish that were acclimated to shelters utilized shelters more frequently than did non-acclimated fish, and the survival rate of acclimated fish was higher than those of fish in the other treatments. These results suggest that pre-release acclimation to shelters improves the post-release survival of hatchery-reared black-spot tuskfish.     

Correlation between cytochrome P450 1A (cyp1a) mRNA expression and ambient phenanthrene and pyrene concentration in Javanese Medaka Oryzias javanicus

Fisheries Science - Cytochrome P450 1A (Cyp1a) catabolizes polycyclic organic compounds. In this study, we sequenced the cyp1a gene from two Javanese medaka&nbsp;Oryzias...     

Development of an efficient bioreactor system for delivering foreign proteins secreted from liver into eggs with a vitellogenin signal in medaka Oryzias latipes

In this study, we developed a novel bioreactor system to deliver and accumulate foreign proteins in eggs using medaka fish Oryzias latipes with the aid of a partial sequence of vitellogenin (Vtg). In teleost fish, Vtg, the hepatically generated precursor of egg yolk proteins, is secreted into the bloodstream and then taken up into eggs. We predicted in silico a probable region (Vtg signal) of Vtg that mediates transportation of proteins from the liver into eggs. Then, we established two transgenic lines expressing the fused proteins including the Vtg signal and each reporter gene, enhanced green fluorescent protein (EGFP) or firefly luciferase (LUC)-fused EGFP, in the liver driven by a liver-specific choriogeninH (chgH) promoter. Each reporter signal was detected from the fertilized eggs spawned by the transgenic females, showing successful transportation of the proteins into the eggs with the Vtg signal. This is the first report demonstrating that the Vtg signal has capability to deliver exogenous proteins into eggs. Because Vtg is a highly conserved protein among most of oviparous organisms, our findings hold promise for establishing bioreactor systems viable in a wide range of organisms.

     

Evaluation of recycled food waste as a partial replacement of fishmeal in diets for the initial feeding of Nile tilapia Oreochromis niloticus

A 70-day feeding trial was conducted to evaluate the suitability of recycled food wastes [food industry waste (FIW) and soy sauce waste (SSW)] as protein sources in the diet of Oreochromis niloticus fry. Diets were formulated that contained 0 and 20–22%, respectively, recycled food wastes, namely D1 (0% recycled food waste), D2 (20% FIW), D3 (10% FIW and SSW, respectively), D4 (20% FIW and tryptophan), and D5 (22% SSW). Although feed efficiency, net protein retention, and protein efficiency were not significantly different among fish on the different diets (p > 0.05), those on D3 had a better growth performance than the controls (D1). Fish fed diet D4 (tryptophan supplement) had a higher final weight gain than those fed D2, in addition to the other growth parameters, but these differences were not significant (p > 0.05), with the exception of total feed intake. D1 produced fish with higher carcass protein, while fish fed on D3 had the highest lipid content. There was no significant difference between groups in terms of carcass moisture and ash contents. These findings show that the proper combination of recycled food waste is suitable for use in the production of fish feed and may ultimately result in reductions in the level of fishmeal in aquafeeds.     

Otolith development and daily increment formation in laboratory-reared larval and juvenile black-spot tuskfish <Emphasis Type="Italic">Choerodon schoenleinii</Emphasis>

Microstructures of lapilli were examined for reared larvae and juveniles of black-spot tuskfish Choerodon schoenleinii. Lapilli of larvae at 1 day after hatching have one diffuse and obscure ring with an otolith radius of 4.3 ± 0.50 μm (mean ± SD, N = 8). The slope and intercept of the regression between the number of days after hatching and increment counts did not differ significantly from one and zero, respectively, indicating that lapillus increments were formed on a daily basis after hatching. There was an ontogenetic shift in the relative values of somatic and otolith growth, which corresponded to the transition from pelagic larvae to settlement stage. Simultaneously, the daily increment width reached the maximum value. These findings suggest that age at maximum value of increment width can be used as an indicator of the planktonic larval duration while settlement mark is not found. Since ontogenetic shift in the relationship between otolith radius and body size was observed, back-calculation of somatic growth in black-spot tuskfish using the otolith radius during the early life stages should be analyzed with caution, and the method requires further validation.