Dietary phytochemicals, of which polyphenols form a considerable part, may affect the risk of obesity-associated chronic diseases such as type 2 diabetes. This article presents an overview on how phytochemicals, especially polyphenols in fruits, vegetables, berries, beverages and herbal medicines, may modify imbalanced lipid and glucose homeostasis thereby reducing the risk of the metabolic syndrome and type 2 diabetes complications.

Evidence from cell culture studies indicates that β-carotene-(BC)-derived apocarotenoid signaling molecules can modulate the activities of nuclear receptors that regulate many aspects of adipocyte physiology. Two BC metabolizing enzymes, the BC-15,15′-oxygenase (Bcmo1) and the BC-9′,10′-oxygenase (Bcdo2) are expressed in adipocytes. Bcmo1 catalyzes the conversion of BC into retinaldehyde and Bcdo2 into β-10′-apocarotenal and β-ionone. Here we analyzed the impact of BC on body adiposity of mice. To genetically dissect the roles of Bcmo1 and Bcdo2 in this process, we used wild-type and Bcmo1 -/- mice for this study. In wild-type mice, BC was converted into retinoids. In contrast, Bcmo1-/- mice showed increased expression of Bcdo2 in adipocytes and β-10′-apocarotenol accumulated as the major BC derivative. In wild-type mice, BC significantly reduced body adiposity (by 28%), leptinemia and adipocyte size. Genome wide microarray analysis of inguinal white adipose tissue revealed a generalized decrease of mRNA expression of peroxisome proliferator-activated receptor γ (PPARγ) target genes. Consistently, the expression of this key transcription factor for lipogenesis was significantly reduced both on the mRNA and protein levels. Despite β-10′-apocarotenoid production, this effect of BC was absent in Bcmo1-/- mice, demonstrating that it was dependent on the Bcmo1-mediated production of retinoids. Our study evidences an important role of BC for the control of body adiposity in mice and identifies Bcmo1 as critical molecular player for the regulation of PPARγ activity in adipocytes

Humanin (HN) is a recently identified neuroprotective and antiapoptotic peptide derived from a portion of the mitochondrial MT-RNR2 gene. We provide bioinformatic and expression data suggesting the existence of 13 MT-RNR2-like nuclear loci predicted to maintain the open reading frames of 15 distinct full-length HN-like peptides. At least ten of these nuclear genes are expressed in human tissues, and respond to staurosporine (STS) and beta-carotene. Sequence comparisons of the nuclear HN isoforms and their homologues in other species reveal two consensus motifs, encompassing residues 5-11 (GFS/NCLLL), and 14-19 (SEIDLP/S). Proline vs serine in position 19 may determine whether the peptide is secreted or not, while threonine in position 13 may be important for cell surface receptor binding. Cytoprotection against the STS-induced apoptosis conferred by the polymorphic HN5 variant, in which threonine in position 13 is replaced with isoleucine, is reduced compared to the wild type HN5 peptide.

OBJECTIVETo investigate the relation between serum concentration of 25-hydroxyvitamin D [25(OH)D] and insulin action and secretion.RESEARCH DESIGN AND METHODSIn a cross-sectional study of 446 Pan-European subjects with the metabolic syndrome, insulin action and secretion were assessed by homeostasis model assessment (HOMA) indexes and intravenous glucose tolerance test to calculate acute insulin response, insulin sensitivity, and disposition index. Serum 25(OH)D was measured by high-performance liquid chromatography/mass spectrometry.RESULTSThe 25(OH)D3 concentration was 57.1 ± 26.0 nmol/l (mean ± SD), and only 20% of the subjects had 25(OH)D3 levels ≥75 nmol/l. In multiple linear analyses, 25(OH)D3 concentrations were not associated with parameters of insulin action or secretion after adjustment for BMI and other covariates.CONCLUSIONSIn a large sample of subjects with the metabolic syndrome, serum concentrations of 25(OH)D3 did not predict insulin action or secretion. Clear evidence that D vitamin status directly influences insulin secretion or action is still lacking.

MicroRNAs (miRNAs) are a family of small, noncoding RNAs that repress gene expression at the post-transcriptional level. Over 700 miRNAs have been identified in the human genome, of which 20% to 30% regulate human protein-coding genes. Functional in vitro studies have shown that miRNAs are critical for endothelial cell gene expression and function. miRNAs were found in atherosclerosis, cardiac hypertrophy, arterial hypertension, coronary artery disease, diabetes, and inflammatory diseases. We review the current knowledge about the role of miRNAs in endothelial cells with emphasis on the regulation of cellular senescence, angiogenesis, and vascular inflammation. It has been shown that miR-34a, miR-217, miR-200, miR-146c, and miR-181a are responsible for the regulation of cell stress and proliferation processes. Proangiogenic factors include miR-130a, miR-210, miR-424, miR-17-92, miR-27-b, let-7f, and miR-217, while miR-221 and miR-222 have antiangiogenic properties. Other known miRNAs, including miR-31, miR17-3p, miR-155, miR-221, miR-222, and miR-126, are important factors in the regulation of vascular inflammation. Studies show that miRNA expression analysis can be used in the diagnosis and treatment of various diseases; however, additional research is needed before it is used in routine clinical setting.