To find new genes that influence liver lipid mass, we performed a genetic screen for zebrafish mutants with hepatic steatosis, a pathological accumulation of fat. The red moon (rmn) mutant develops hepatic steatosis as maternally deposited yolk is depleted. Conversely, hepatic steatosis is suppressed in rmn mutants by adequate nutrition. Adult rmn mutants show increased liver neutral lipids and induction of hepatic lipid biosynthetic genes when fasted. Positional cloning of the rmn locus reveals a loss-of-function mutation in slc16a6a (solute carrier family 16a, member 6a), a gene that we show encodes a transporter of the major ketone body b-hydroxybutyrate. Restoring wild-type zebrafish slc16a6a expression or introducing human SLC16A6 in rmn mutant livers rescues the mutant phenotype. Radiotracer analysis confirms that loss of Slc16a6a function causes diversion of livertrapped ketogenic precursors into triacylglycerol. Underscoring the importance of Slc16a6a to normal fasting physiology, previously fed rmn mutants are more sensitive to death by starvation than are wild-type larvae. Our unbiased, forward genetic approach has found a heretofore unrecognized critical step in fasting energy metabolism: hepatic ketone body transport. Since b-hydroxybutyrate is both a major fuel and a signaling molecule in fasting, the discovery of this transporter provides a new direction for modulating circulating levels of ketone bodies in metabolic diseases.

Previous investigations in gene expression changes in blood after radiation exposure have highlighted its potential to provide biomarkers of exposure. Here, FDXR transcriptional changes in blood were investigated in humans undergoing a range of external radiation exposure procedures covering several orders of magnitude (cardiac fluoroscopy, diagnostic computed tomography (CT)) and treatments (total body and local radiotherapy). Moreover, a method was developed to assess the dose to the blood using physical exposure parameters. FDXR expression was significantly up-regulated 24 hr after radiotherapy in most patients and continuously during the fractionated treatment. Significance was reached even after diagnostic CT 2 hours post-exposure. We further showed that no significant differences in expression were found between ex vivo and in vivo samples from the same patients. Moreover, potential confounding factors such as gender, infection status and anti-oxidants only affect moderately FDXR transcription. Finally, we provided a first in vivo dose-response showing dose-dependency even for very low doses or partial body exposure showing good correlation between physically and biologically assessed doses. In conclusion, we report the remarkable responsiveness of FDXR to ionising radiation at the transcriptional level which, when measured in the right time window, provides accurate in vivo dose estimates.

SUMMARYHere we present the presence of adiponectin and adiponectin receptors [type 1 (adipoR1) and type 2 (adipoR2)] in rainbow trout (Oncorhynchus mykiss) tissues and cell cultures together with the response to different scenarios. In response to fasting, adiponectin expression was up-regulated in adipose tissue, while the expression of its receptors increased in white and red muscle. Insulin injection decreased adipoR1 expression in white and red muscles. We deduce that the adipoRs in trout muscle show opposite responses to increasing insulin plasma levels, which may maintain sensitivity to insulin in this tissue. Adiponectin expression was inhibited by the inflammatory effect of lipopolysaccharide (LPS) in adipose tissue and red muscle. Moreover, results indicate that LPS may lead to mobilization of fat reserves, increasing adipoR1 expression in adipose tissue. The effects of LPS could be mediated through tumour necrosis factor  (TNF), at least in red muscle. Insulin, growth hormone and TNF all diminished expression of adipoR2 in adipocytes and adipoR1 in myotubes, while insulin increased the expression of adipoR2 in the muscle cells. Adiponectin activates Akt in rainbow trout myotubes, which may lead to an increase in fatty acid uptake and oxidation. Overall, our results show that the adiponectin system responds differently to various physiological challenges and that it is hormonally controlled in vivo and in vitro. To the best of our knowledge, this is the first time this has been demonstrated in teleosts, and it may be a valuable contribution to our understanding of adipokines in fish.

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The effects of a double replacement of fish oil (FO) and fish meal (FM) by dietary vegetable ingredients in juvenile gilthead sea bream (Sparus aurata L. 1758) on some indices of lipid metabolism and plasma insulin levels were analysed. Four experimental diets with a replacement of 75% of FM by plant proteins (PP) were administered. Added oil was either FO (75PP/FO diet), or a vegetable oil mix (VO), replacing 33%, 66% or 100% of FO (75PP/33VO, 75PP/66VO, 75PP/100VO diets). Another diet with 50% of substitution of FM by PP and with 100% of VO was also tested (50PP/100VO diet). Final body weight was similar in all diet groups, except for the 75PP/100VO group, which presented lower values. Circulating insulin levels increased with feed administration in all groups and no differences between diets were observed, with the exception of the 75PP/FO group, which presented higher plasma insulin values. In adipose tissue, glucose‐6‐phosphate dehydrogenase and malic enzyme activities decreased with the inclusion of vegetable oil, especially 5 h after feeding. Diet had no significant effect on the hepatic activity of either enzyme. Lipoprotein lipase activity decreased in white muscle and adipose tissue with the replacement of fish oil in 75PP diets, 5 h after feeding. In conclusion, the use of a combined replacement of fish oil and fish meal by vegetable ingredients in gilthead sea bream permits satisfactory growth, with moderate changes in tissue lipogenesis and lipid uptake.