How Zinc Transporters in Escherichia coli Influence Ageing in the Nematode Caenorhabditis elegans

Gut microbes play an important role in mammalian physiology. Escherichia coli not only provide the Caenorhabditis elegans with vital nutrients but also influence worms lifespan. Studying such interactions could help us to understand how intestinal microbes influence mammalian ageing. A recent gene deletion study of 1041 E. coli in our lab identified 9 genes that are involved in the increase of worm’s lifespan. One gene identified was ZnuB, which forms part of the high affinity znuABC zinc ABC transporters, plays an important role in zinc homeostasis, and has been suggested to play a role in increased lifespan. To validate this hypothesis, levels of zinc were measured using ICP-MS in znuA, znuB, and znuC mutant bacteria and worms fed with the mutants, and compared with zinc levels in WT bacteria and C. elegans fed with WT bacteria. Zinc levels were also measured in LB and NGM media. It was found that although bacteria and worms could obtain zinc from LB media, the level of zinc was lower in worms and the three mutant bacteria than in WT bacteria alone. Lifespan of worms fed with those mutants was investigated. Worms fed with znuB and znuC bacteria showed extended lifespan, compered to worms fed with znuA bacteria. Reduced fecundity was observed in experimental worms fed with mutant as compared to worms fed with WT bacteria. Moreover, the worms fed with the znuB showed a delay in the reproductive cycle. These results suggest that reducing zinc concentration itself in the mutant bacteria does not make the worms live longer, but the mutation in the znuB could produce different effects. Results of zinc supplement experiments using mutants showed reversal effect on worm developmental delay when fed with znuB and zinc supplements. These results show that the znuB not only plays an important role in zinc uptake by bacteria, but also affects the lifespan of C. elegans

Sex-dimorphism in Cardiac Nutrigenomics: effect of Trans fat and/or Monosodium Glutamate consumption

<p>Abstract</p> <p>Background</p> <p>A paucity of information on biological sex-specific differences in cardiac gene expression in response to diet has prompted this present nutrigenomics investigation.</p> <p>Sexual dimorphism exists in the physiological and transcriptional response to diet, particularly in response to high-fat feeding. Consumption of <it>Trans</it>-fatty acids (TFA) has been linked to substantially increased risk of heart disease, in which sexual dimorphism is apparent, with males suffering a higher disease rate. Impairment of the cardiovascular system has been noted in animals exposed to Monosodium Glutamate (MSG) during the neonatal period, and sexual dimorphism in the growth axis of MSG-treated animals has previously been noted. Processed foods may contain both TFA and MSG.</p> <p>Methods</p> <p>We examined physiological differences and changes in gene expression in response to TFA and/or MSG consumption compared to a control diet, in male and female C57BL/6J mice.</p> <p>Results</p> <p>Heart and % body weight increases were greater in TFA-fed mice, who also exhibited dyslipidemia (P < 0.05). Hearts from MSG-fed females weighed less than males (P < 0.05). 2-factor ANOVA indicated that the TFA diet induced over twice as many cardiac differentially expressed genes (DEGs) in males compared to females (P < 0.001); and 4 times as many male DEGs were downregulated including <it>Gata4</it>, <it>Mef2d </it>and <it>Srebf2</it>. Enrichment of functional Gene Ontology (GO) categories were related to transcription, phosphorylation and anatomic structure (P < 0.01). A number of genes were upregulated in males and downregulated in females, including pro-apoptotic histone deacetylase-2 (HDAC2). Sexual dimorphism was also observed in cardiac transcription from MSG-fed animals, with both sexes upregulating approximately 100 DEGs exhibiting sex-specific differences in GO categories. A comparison of cardiac gene expression between all diet combinations together identified a subset of 111 DEGs significant only in males, 64 DEGs significant in females only, and 74 transcripts identified as differentially expressed in response to dietary manipulation in both sexes.</p> <p>Conclusion</p> <p>Our model identified major changes in the cardiac transcriptional profile of TFA and/or MSG-fed mice compared to controls, which was reflected by significant differences in the physiological profile within the 4 diet groups. Identification of sexual dimorphism in cardiac transcription may provide the basis for sex-specific medicine in the future.</p

Regulation of Fat Storage and Reproduction by Krüppel-Like Transcription Factor KLF3 and Fat-Associated Genes in Caenorhabditis elegans

https://egrove.olemiss.edu/meek_rfkspeech/1017/thumbnail.jp

Identification of the tetraspanin CD82 as a new barrier to xenotransplantation

Significant immunological obstacles are to be negotiated before xenotransplantation becomes a clinical reality. An initial rejection of transplanted vascularized xenograft is attributed to Galα1,3Galβ1,4GlcNAc-R (Galα1,3-Gal)-dependent and -independent mechanisms. Hitherto, no receptor molecule has been identified that could account for Galα1,3-Gal-independent rejection. In this study, we identify the tetraspanin CD82 as a receptor molecule for the Galα1,3-Gal-independent mechanism. We demonstrate that, in contrast to human undifferentiated myeloid cell lines, differentiated cell lines are capable of recognizing xenogeneic porcine aortic endothelial cells in a calcium-dependent manner. Transcriptome-wide analysis to identify the differentially expressed transcripts in these cells revealed that the most likely candidate of the Galα1,3-Gal-independent recognition moiety is the tetraspanin CD82. Abs to CD82 inhibited the calcium response and the subsequent activation invoked by xenogeneic encounter. Our data identify CD82 on innate immune cells as a major "xenogenicity sensor" and open new avenues of intervention to making xenotransplantation a clinical reality

Effect of dietary monosodium glutamate on trans fat-induced nonalcoholic fatty liver disease

The effects of dietary monosodium glutamate (MSG) on trans-fatty acid (TFA)-induced nonalcoholic fatty liver disease (NAFLD) are addressed in an animal model. We used Affymetrix microarray analysis to investigate hepatic gene expression and the contribution of visceral white adipose tissue (WAT) to diet-induced NAFLD. Trans-fat feeding increased serum leptin, FFA, HDL-cholesterol (HDL-C), and total cholesterol (T-CHOL) levels, while robustly elevating the expression of genes involved in hepatic lipogenesis, including the transcription factor sterol-regulatory element binding protein 1c. Histological examination revealed hepatic macrosteatosis in TFA-fed animals. Conversely, dietary MSG at doses similar to human average daily intake caused hepatic microsteatosis and the expression of β-oxidative genes. Serum triglyceride, FFA, and insulin levels were elevated in MSG-treated animals. The abdominal cavities of TFA- or MSG-treated animals had increased WAT deposition compared with controls. Microarray analysis of WAT gene expression revealed increased lipid biosynthetic gene expression, together with a 50% decrease in the key transcription factor Ppargc1a. A combination of TFA+MSG resulted in the highest levels of serum HDL-C, T-CHOL, and leptin. Microarray analysis of TFA+MSG-treated livers showed elevated expression of markers of hepatic inflammation, lipid storage, cell damage, and cell cycle impairment. TFA+MSG mice also had a high degree of WAT deposition and lipogenic gene expression. Levels of Ppargc1a were further reduced to 25% by TFA+MSG treatment. MSG exacerbates TFA-induced NAFLD