Intake of Farmed Atlantic Salmon Fed Soybean Oil Increases Insulin Resistance and Hepatic Lipid Accumulation in Mice

Background

To ensure sustainable aquaculture, fish derived raw materials are replaced by vegetable ingredients. Fatty acid composition and contaminant status of farmed Atlantic salmon (Salmo salar L.) are affected by the use of plant ingredients and a spillover effect on consumers is thus expected. Here we aimed to compare the effects of intake of Atlantic salmon fed fish oil (FO) with intake of Atlantic salmon fed a high proportion of vegetable oils (VOs) on development of insulin resistance and obesity in mice.

Methodology/principal findings

Atlantic salmon were fed diets where FO was partly (80%) replaced with three different VOs; rapeseed oil (RO), olive oil (OO) or soy bean oil (SO). Fillets from Atlantic salmon were subsequently used to prepare Western diets (WD) for a mouse feeding trial. Partial replacement of FO with VOs reduced the levels of polychlorinated biphenyls (PCB) and dichloro-diphenyl-tricloroethanes (DDT) with more than 50% in salmon fillets, in WDs containing the fillets, and in white adipose tissue from mice consuming the WDs. Replacement with VOs, SO in particular, lowered the n−3 polyunsaturated fatty acid (PUFA) content and increased n−6 PUFA levels in the salmon fillets, in the prepared WDs, and in red blood cells collected from mice consuming the WDs. Replacing FO with VO did not influence obesity development in the mice, but replacement of FO with RO improved glucose tolerance. Compared with WD-FO fed mice, feeding mice WD-SO containing lower PCB and DDT levels but high levels of linoleic acid (LA), exaggerated insulin resistance and increased accumulation of fat in the liver.

Conclusion/Significance

Replacement of FO with VOs in aqua feed for farmed salmon had markedly different spillover effects on metabolism in mice. Our results suggest that the content of LA in VOs may be a matter of concern that warrants further investigation.     

Site-specific mutagenesis and domain substitutions in the loading module of the nystatin polyketide synthase,and their effects on nystatin biosynthesis in Streptomyces noursei

The loading module for the nystatin polyketide synthase (PKS) in Streptomyces noursei is represented by the NysA protein composed of a ketosynthase (KS(S)), acyltransferase, dehydratase, and an acyl carrier protein. The absolute requirement of this protein for initiation of nystatin biosynthesis was demonstrated by the in-frame deletion of the nysA gene in S. noursei. The role of the NysA KS(S) domain, however, remained unclear, since no data on the significance of the "active site" serine (Ser-170) residue in the loading modules of type I PKSs were available. Site-specific mutagenesis of Ser-170 both in the wild-type NysA and in the hybrid loading module containing malonyl-specific acyltransferase domain from the extender module had no effect on nystatin biosynthesis. A second mutation (S413N) of the NysA KS(S) domain was discovered that completely abolished the ability of the hybrids to restore nystatin biosynthesis, presumably by affecting the ability of the resulting proteins to catalyze the required substrate decarboxylation. In contrast, NysA and its Ser-170 mutants bearing the same S413N mutation were able to restore nystatin production to significant levels, probably by using acetyl-CoA as a starter unit. Together, these data suggest that the KS(S) domain of NysA differs from the KS(Q) domains found in the loading modules of several PKS type I systems in that the active site residue is not significant for its activity.     

Circadian variations in clock gene expression of human bone marrow CD34+ cells

Time-dependent variations in clock gene expression have recently been observed in mouse hematopoietic cells, but the activity of these genes in human bone marrow (BM) has so far not been investigated. Since such data can be of considerable clinical interest for monitoring the dynamics in stem/progenitor cells, the authors have studied mRNA expression of the clock genes hPer1 , hPer2, hCry1, hCry2, hBmal1, hRev-erb alpha, and hClock in human hematopoietic CD34-positive (CD34( +)) cells. CD34(+) cells were isolated from the BM samples obtained from 10 healthy men at 6 times over 24 h. In addition, clock gene mRNA expression was analyzed in the whole BM in 3 subjects. Rhythms in serum cortisol, growth hormone, testosterone, and leukocyte counts documented that subjects exhibited standardized circadian patterns. All 7 clock genes were expressed both in CD34(+) cells and the whole BM, with some differences in magnitude between the 2 cell populations. A clear circadian rhythm was shown for hPer1, hPer2, and hCry2 expression in CD34(+) cells and for hPer1 in the whole BM, with maxima from early morning to midday. Similar to mouse hematopoietic cells, h Bmal1 was not oscillating rhythmically. The study demonstrates that clock gene expression in human BM stem/progenitor cells may be developmentally regulated, with strong or weaker circadian profiles as compared to those reported in other mature tissues.