Early postnatal caloric restriction protects adult male intrauterine growth-restricted offspring from obesity.

Postnatal ad libitum caloric intake superimposed on intrauterine growth restriction (IUGR) is associated with adult-onset obesity, insulin resistance, and type 2 diabetes mellitus (T2DM). We hypothesized that this paradigm of prenatal nutrient deprivation-induced programming can be reversed with the introduction of early postnatal calorie restriction. Ten-month-old male rats exposed to either prenatal nutrient restriction with ad libitum postnatal intake (IUGR), pre- and postnatal nutrient restriction (IPGR), or postnatal nutrient restriction limited to the suckling phase (50% from postnatal [PN]1 to PN21) (PNGR) were compared with age-matched controls (CON). Visceral adiposity, metabolic profile, and insulin sensitivity by hyperinsulinemic-euglycemic clamps were examined. The 10-month-old male IUGR group had a 1.5- to 2.0-fold increase in subcutaneous and visceral fat (P < 0.0002) while remaining euglycemic, insulin sensitive, inactive, and exhibiting metabolic inflexibility (Vo(2)) versus CON. The IPGR group remained lean, euglycemic, insulin sensitive, and active while maintaining metabolic flexibility. The PNGR group was insulin sensitive, similar to IPGR, but less active while maintaining metabolic flexibility. We conclude that IUGR resulted in obesity without insulin resistance and energy metabolic perturbations prior to development of glucose intolerance and T2DM. Postnatal nutrient restriction superimposed on IUGR was protective, restoring metabolic normalcy to a lean and active phenotype

Akt regulates the expression of MafK, synaptotagmin I, and syntenin-1, which play roles in neuronal function

<p>Abstract</p> <p>Background</p> <p>Akt regulates various cellular processes, including cell growth, survival, and metabolism. Recently, Akt's role in neurite outgrowth has also emerged. We thus aimed to identify neuronal function-related genes that are regulated by Akt.</p> <p>Methods</p> <p>We performed suppression subtractive hybridization on two previously established PC12 sublines, one of which overexpresses the wild-type (WT) form and the other, the dominant-negative (DN) form of Akt. These sublines respond differently to NGF's neuronal differentiation effect.</p> <p>Results</p> <p>A variety of genes was identified and could be classified into several functional groups, one of which was developmental processes. Two genes involved in neuronal differentiation and function were found in this group. v-Maf musculoaponeurotic fibrosarcoma oncogene homolog K (MafK) induces the neuronal differentiation of PC12 cells and immature telencephalon neurons, and synaptotagmin I (SytI) is essential for neurotransmitter release. Another gene, <it>syntenin-1 </it>(<it>Syn-1</it>) was also recognized in the same functional group into which <it>MafK </it>and <it>SytI </it>were classified. Syn-1 has been reported to promote the formation of membrane varicosities in neurons. Quantitative reverse transcription polymerase chain reaction analyses show that the transcript levels of these three genes were lower in PC12 (WT-Akt) cells than in parental PC12 and PC12 (DN-Akt) cells. Furthermore, treatment of PC12 (WT-Akt) cells with an Akt inhibitor resulted in the increase of the expression of these genes and the improvement of neurite outgrowth. These results indicate that dominant-negative or pharmacological inhibition of Akt increases the expression of <it>MafK</it>, <it>SytI</it>, and <it>Syn-1 </it>genes. Using lentiviral shRNA to knock down endogenous Syn-1 expression, we demonstrated that Syn-1 promotes an increase in the numbers of neurites and branches.</p> <p>Conclusions</p> <p>Taken together, these results indicate that Akt negatively regulates the expression of <it>MafK</it>, <it>SytI</it>, and <it>Syn-1 </it>genes that all participate in regulating neuronal integrity in some way or another.</p

Modeling of endothelial cell dysfunction using human induced pluripotent stem cells derived from patients with end-stage renal disease

Background Endothelial cell (EC) dysfunction is a frequent feature in patients with end-stage renal disease (ESRD). The aim of this study was to generate human induced pluripotent stem cells, differentiate ECs (hiPSC-ECs) from patients with ESRD, and appraise the usefulness of hiPSC-ECs as a model to investigate EC dysfunction. Methods We generated hiPSCs using peripheral blood mononuclear cells (PBMCs) isolated from three patients with ESRD and three healthy controls (HCs). Next, we differentiated hiPSC-ECs using the generated hiPSCs and assessed the expression of endothelial markers by immunofluorescence. The differentiation efficacy, EC dysfunction, and molecular signatures of EC-related genes based on microarray analysis were compared between the ESRD and HC groups. Results In both groups, hiPSCs and hiPSC-ECs were successfully obtained based on induced pluripotent stem cell or EC marker expression in immunofluorescence and flow cytometry. However, the efficiency of differentiation of ECs from hiPSCs was lower in the ESRD-hiPSCs than in the HC-hiPSCs. In addition, unlike HC-hiPSC-ECs, ESRD-hiPSC-ECs failed to form interconnecting branching point networks in an in vitro tube formation assay. During microarray analysis, transcripts associated with oxidative stress and inflammation were upregulated and transcripts associated with vascular development and basement membrane extracellular matrix components were downregulated in ESRD-hiPSC-ECs relative to in HC-hiPSC-ECs. Conclusion ESRD-hiPSC-ECs showed a greater level of EC dysfunction than HC-hiPSC-ECs did based on functional assay results and molecular profiles. hiPSC-ECs may be used as a disease model to investigate the pathophysiology of EC dysfunction in ESRD

Comparative transcriptional analysis of caffeoyl-coenzyme A 3-O-methyltransferase from Hibiscus cannabinus L., during developmental stages in various tissues and stress regulation,”

Abstract We have cloned a full-length gene, putatively encoding for caffeoyl-coenzyme A 3-O-methyltransferase (CCoAOMT), an important enzyme involved in lignin biosynthesis, from kenaf (Hibiscus cannabinus L.). Herein, we investigated the expression pattern of a CCoAOMT orthologue from various tissues and organs during development, and in response to different environmental cues. The full-length CCoAOMT orthologue of kenaf consists of a 744 bp open reading frame (ORF), encoding for 247 amino acids of 27.91 kDa and an isoelectric point (pI) of 5.43. The deduced amino acids of CCoAOMT evidenced a high degree of identity (up to 84%) with other plant CCoAOMT sequences. Phylogenetic analysis demonstrated its close relationship with the CCoAOMT of Gossypium hirsutum (ACQ59096). Kenaf CCoAOMT harbors eight highly conserved motifs: A, B, and C are putative S-adenosylmethioine (SAM)-binding motifs and D, E, F, G, and H are CCoAOMT signature motifs. According to quantitative real-time reverse transcriptase polymerase chain reaction (q-PCR) analysis, the kenaf CCoAOMT transcript was detected in all plant tissues and organs, whereas the highest expression was noted in mature flower tissues, which indicates that it might be involved in the flower development or in the biosynthesis of flower specific compound. All the treatments highly induced the expression of CCoAOMT transcripts in the stems of 3-week-old kenaf, which indicates that it might have a role in stress regulatory pathway. Among the treatments, the cold and H 2 O 2 -treated samples evidenced the highest levels of expression at 6 and 24 h after treatment, respectively, whereas the wounded and NaCl-treated samples evidenced lower expression levels, which suggest that different signaling networks are involved for stress mediated up regulation of HcCCoAOMT transcripts. The highest transcript level of CCoAOMT was detected at either early (within 12 h of treatments) or intermediate (24 h after treatments) time points of treatments, except drought treated sample. Early induction was observed in the case of H 2 O 2 and SA (salicylic acid), and intermediate induction occurring as the result of wounding, NaCl, cold and ABA (abscisic acid). Whereas drought treated sample showed highest expression at seven days after treatment. MeJA (methyl jasmonic acid) treatment showed a complex biphasic expression which is different from others. In summary, we have cloned and characterized a full-length gene putatively encoding for CCoAOMT, which also showed stress responsive differential expression

A Survey of Diabetic Educators and Patients for the Revision of Korean Food Exchange Lists

BackgroundFood exchange lists are one of the main methods of nutritional education. However, Korean food exchange lists have not been revised since 1994. Therefore, we surveyed the opinions of diabetes educators and patients with diabetes regarding the need for revision of the current food exchange lists.MethodsFor two weeks beginning on 10 March 2008, a 12-item questionnaire regarding the opinion and need for revision of the current food exchange lists was e-mailed to diabetes educators nationwide. Another 15-question survey was administered to patients with diabetes in 13 hospitals located in the Seoul and Gyeonggi regions of Korea.ResultsWe obtained survey responses from 101 diabetes educators and 209 patients; 65 (64.3%) of the educators answered that the current food exchange lists should be revised. The items that needed revision were the glycemic index, addition of new foods and reaffirmation of exchange standard amounts. The patients demanded specific education about choosing appropriate foods, a balanced meal plan, proper snacks, and dining intake.ConclusionOur survey results demonstrate the need to revise the Korean food exchange lists. This process should focus on glycemic index, the addition of new foods and reconfirmation of one exchange reference unit