Although a requirement of zinc (Zn) for normal brain development is well documented, the extent to which Zn can modulate neuronal proliferation and apoptosis is not clear. Thus, we investigated the role of Zn in the regulation of these two critical events. A low Zn availability leads to decreased cell viability in human neuroblastoma IMR-32 cells and primary cultures of rat cortical neurons. This occurs in part as a consequence of decreased cell proliferation and increased apoptotic cell death. In IMR-32 cells, Zn deficiency led to the inhibition of cell proliferation through the arrest of the cell cycle at the G 0 /G 1 phase. Zn deficiency induced apoptosis in both proliferating and quiescent neuronal cells via the intrinsic apoptotic pathway. Reductions in cellular Zn triggered a translocation of the pro-apoptotic protein Bad to the mitochondria, cytochrome c release, and caspase-3 activation. Apoptosis is the resultant of the inhibition of the prosurvival extracellular-signal-regulated kinase, the inhibition of nuclear factor-kappa B, and associated decreased expression of antiapoptotic proteins, and to a direct activation of caspase-3. A deficit of Zn during critical developmental periods can have persistent effects on brain function secondary to a deregulation of neuronal proliferation and apoptosis.

This article is available online at http://www.jlr.org Health consequences associated with low intakes of the long-chain, marine omega-3 (n3) FAs have become a central issue in nutritional lipid research. The United States Department of Agriculture's 2010 Dietary Guidelines recommend consumption of 8 ounces per week of fi sh, providing an average of 250 mg eicosapentaenoic acid (20:5n3) and docosahexaenoic acid (22:6n3) per day for prevention of heart disease ( 1 ). Moreover, public awareness regarding the potential health benefi ts of n3 FAs has spurred an increase in fatty fi sh and fi sh oil consumption ( 2 ).Although the mechanisms by which n3-HUFAs improve health are still being explored, it is clear that increasing n3-HUFA intake can decrease the risk of cardiovascular disease (CVD) in at-risk individuals ( 3-5 ). In hyperlipidemic subjects, treatment with high doses of n3-HUFAs lowers triglycerides ( 6 ) and improves total:HDL cholesterol ratios ( 6, 7 ), a surrogate marker associated with a reduction in CVD risk. The n3-HUFAs 20:5n3 and 22:6n3 also reduce infl ammatory responses in a range of conditions ( 8-10 ). A well-accepted effect of n3-HUFA supplementation is a reduction in thrombin-stimulated platelet aggregation due to decreased platelet cyclooxygenase metabolism ( 11 ). More recently, a cyclooxygenase-independent diminution of platelet sensitivity to collagen has been reported after P-OM3 treatment ( 12 ). Thus, an increase in the anti-infl ammatory n3-HUFAs, which lowers the more proinfl ammatory n6-HUFAs ( 13-15 ), at least partially explains the health benefi ts of n3-HUFA consumption ( 8-10 ). 5306-51530-019-00D (J.W.N.), National Institute of Food and Agriculture National Needs Fellowship grant 2008-38420-04759 (A.H.K.), and by grant LVZ112860 from GlaxoSmithKline (G.C.S.) Abbreviations: CVD, cardiovascular disease; HUFA, highly unsaturated fatty acid; P-OM3, prescription omega-3 acid ethyl esters; RBC, red blood cell.

High-protein diets induce alterations in metabolism that may prevent diet-induced obesity. However, little is known as to whether different protein sources consumed at normal levels may affect diet-induced obesity and associated co-morbidities. We fed obesity-prone male C57BL/6J mice high-fat, high-sucrose diets with protein sources of increasing endogenous taurine content, i.e., chicken, cod, crab and scallop, for 6 weeks. The energy intake was lower in crab and scallop-fed mice than in chicken and cod-fed mice, but only scallop-fed mice gained less body and fat mass. Liver mass was reduced in scallop-fed mice, but otherwise no changes in lean body mass were observed between the groups. Feed efficiency and apparent nitrogen digestibility were reduced in scallop-fed mice suggesting alterations in energy utilization and metabolism. Overnight fasted plasma triacylglyceride, non-esterified fatty acids, glycerol and hydroxy-butyrate levels were significantly reduced, indicating reduced lipid mobilization in scallop-fed mice. The plasma HDL-to-total-cholesterol ratio was higher, suggesting increased reverse cholesterol transport or cholesterol clearance in scallop-fed mice in both fasted and non-fasted states. Dietary intake of taurine and glycine correlated negatively with body mass gain and total fat mass, while intake of all other amino acids correlated positively. Furthermore taurine and glycine intake correlated positively with improved plasma lipid profile, i.e., lower levels of plasma lipids and higher HDL-to-total-cholesterol ratio. In conclusion, dietary scallop protein completely prevents high-fat, high-sucrose-induced obesity whilst maintaining lean body mass and improving the plasma lipid profile in male C57BL/6J mice.Electronic supplementary materialThe online version of this article (doi:10.1007/s00726-014-1715-1) contains supplementary material, which is available to authorized users.

Transcription factors AP-1, NF- κB and NFAT are central to brain development by regulating the expression of genes that modulate cell proliferation, differentiation, apoptosis, and synaptic plasticity. This work investigated the consequences of feeding zinc deficient and marginal zinc diets to rat dams during gestation on the modulation of AP-1, NF- κB and NFAT in fetal brain. Sprague-Dawley rats were fed from gestation day 0 a control diet ad libitum (25 μg zinc/g diet, C), a zinc deficient diet ad libitum (0.5 μg zinc/g diet, ZD), the control diet in the amounts eaten by the ZD rats (restrict fed, RF), or a diet containing a marginal zinc concentration ad libitum (10 μg zinc/g diet, MZD) until gestation day 19. AP-1-DNA binding was higher (50-190%) in nuclear fraction isolated from ZD, RF and MZD fetal brains compared to controls. In MZD fetal brain high levels of activation of the upstream mitogen-activated protein kinases JNK and p38 and low levels of ERK phosphorylation were observed. Total levels of NF- κB and NFAT activation were higher or similar in the ZD and MZD groups than in controls, respectively. However, NF- κB- and NFAT-DNA binding in nuclear fractions was markedly lower in ZD and MZD fetal brain than in controls (50-80%). The latter could be related to zinc deficiency-associated alterations of the cytoskeleton which is required for NF- κB and NFAT nuclear transport. In summary, suboptimal zinc nutrition during gestation could cause long term effects on brain function, partially through a deregulation of transcription factors AP-1, NF- κB and NFAT.