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Abstract: Ninety-eight genes/ESTs with differential expressions in epididymal adipose tissue of fed and 3-day fasting (F3) rats were identified by microarray analysis. Genes for lipogenesis, glycolysis, and glucose aerobic oxidation were decreased in response to starvation. Further study was performed to investigate the expression patterns of these genes in rat tissues after short- and long-term starvations. The results of the increased expression of the pyruvate dehydrogenase kinase 4 (PDK4) gene and decreased pyruvate dehydrogenase (PDH) in rat muscle together with decreased fatty acid synthase (FAS) in rat adipose tissue after 1 day of fasting (F1) suggested from transcriptional level that glucose aerobic oxidation was down-regulated in rat muscle and synthesis of saturated fatty acids was inhibited in rat adipose tissue after short-term fasting. It was noted that the transcriptions of genes involved in the fatty acid oxidation, such as very-long-chain Acyl-CoA dehydrogenase (LCAH), Acyl-CoA oxidase (ACO), carnitine palmitoyltransferase-I (CPT-I), and carntine-acylcarnitine translocase(CAT)L, were greatly increased in F1 rat liver, then began to decrease in F3 and 5-day fasting (F5) rat liver, combined with significantly increased serum non-esterified fatty acids (NEFA) in F1 rats and increased urea in F5 rats, suggesting that inhibition of the oxidation of lipid and not the decreased availability of these fuels may play an important role in the phase II–phase III of fasting transition in the long-term fasting rats. [Copyright &y& Elsevier]

In order to fully understand the physiological functions of adipose tissue, especially its secretory functions, and to provide a basis for the identification of novel obesity related genes, the gene expression profiling of human visceral adipose tissue was established by using cDNA array. 33P-labelled cDNA, derived from visceral adipose tissue total RNA, was hybridized to a cDNA array containing over 16,000 expressed sequence-tagged clones which represent human singleton genes. The expressed sequence tag (EST) was considered to be expressed in visceral adipose tissue when the ratio of signal to noise was greater than or equal to 2. The results were analyzed with bioinformatics. Totally, 8230 genes were found to be expressed in visceral adipose tissue with 5200 known genes and 3030 known ESTs. Most of 84 secretory proteins, 120 receptors, and 74 transcription factors expressed in adipose tissue were newly identified. Many appetite-regulating related peptides or receptors and some reproduction-related genes were first found to be expressed in adipose tissue. Eight autocrine/paracrine systems were described for the first time in the visceral adipose tissue. These results clearly demonstrate that the visceral adipose tissue has important secretory functions and there is a complex local autocrine/paracrine regulatory network. The present work suggests that the visceral adipose tissue is an important component of the neuroendocrine-immune network and plays an important role in regulating appetite not only via endocrine but also via autocrine/paracrine systems. The visceral adipose tissue might also play a role in regulating reproduction and sexual function. [Copyright &y& Elsevier]

Autophagy is a catabolic process to maintain intracellular homeostasis that degrades damaged proteins and organelles in mammalian cells. Podocytes are crucial for maintaining the normal function of the glomerular filtration barrier. In the present study, we aimed to investigate the high glucose-induced cell injury in human podocytes and the protective role of autophagy in this process. Here we show that the autophagy activity was decreased under the high glucose conditions and 72 h of high glucose exposure inhibited the cell viablity and aggravated cell injury. Moreover, autophagy upregulation by Sequestosome 1 (p62/SQSM1) knockdown ameliorated this cell injury and relieved insulin resistance. Collectively, the present study proposed a novel autophagy involved mechanism of high glucose-induced cell injury. The present study deepens our understanding of the role of autophagy in the pathogenesis of diabetic nephropathy and provided potential therapeutic strategy for diabetic nephropathy. [ABSTRACT FROM AUTHOR]

Abstract: Synaptotagmins (Syts) are calcium-binding proteins which are conserved from nematodes to humans. Fifteen Syts have been identified in mammalian species. Syt I is recognized as a Ca2+ sensor for the synchronized release of synaptic vesicles in some types of neurons, but its role in the secretion of dense core vesicles (DCVs) remains unclear. The function of Syt IV is of particular interest because it is rapidly up-regulated by chronic depolarization and seizures. Using RNAi-mediated gene silencing, we have explored the role of Syt I and IV on secretion in a pituitary gonadotrope cell line. Downregulation of Syt IV clearly reduced Ca2+-triggered exocytosis of dense core vesicles (DCVs) in LβT2 cells. Syt I silencing, however, had no effect on vesicular release. [Copyright &y& Elsevier]

Abstract: Synaptotagmins (Syts) constitute a large family of at least 16 members and individual Syt isoforms exhibit distinct Ca2+-binding properties and subcellular localization. It remains to be demonstrated whether multiple Syt isoforms can function independently or cooperatively on certain type of vesicle. In the current study, we have developed NPY-pHluorin to specifically assess exocytosis of large dense core vesicles (LDCVs) and studied the requirement of Syt I and Syt IX for LDCV exocytosis in PC12 cells. We found that down-regulation of both Syt I and Syt IX resulted in a significant loss of Ca2+-dependent LDCV exocytosis. Moreover, our results suggest Syt I and Syt IX play redundant role in controlling the choice of fusion modes. Down-regulation of both Syt I and Syt IX renders more fusion in the kiss-and-run mode. We conclude that Syt I and Syt IX function redundantly in Ca2+-sensing and fusion pore dilation on LDCVs in PC12 cells. [Copyright &y& Elsevier]