Curcumin Prevents High Fat Diet Induced Insulin Resistance and Obesity via Attenuating Lipogenesis in Liver and Inflammatory Pathway in Adipocytes

Background: Mechanisms underlying the attenuation of body weight gain and insulin resistance in response to high fat diet (HFD) by the curry compound curcumin need to be further explored. Although the attenuation of the inflammatory pathway is an accepted mechanism, a recent study suggested that curcumin stimulates Wnt signaling pathway and hence suppresses adipogenic differentiation. This is in contrast with the known repressive effect of curcumin on Wnt signaling in other cell lineages. Methodology and Principal Findings: We conducted the examination on low fat diet, or HFD fed C57BL/6J mice with or without curcumin intervention for 28 weeks. Curcumin significantly attenuated the effect of HFD on glucose disposal, body weight/fat gain, as well as the development of insulin resistance. No stimulatory effect on Wnt activation was observed in the mature fat tissue. In addition, curcumin did not stimulate Wnt signaling in vitro in primary rat adipocytes. Furthermore, curcumin inhibited lipogenic gene expression in the liver and blocked the effects of HFD on macrophage infiltration and the inflammatory pathway in the adipose tissue. Conclusions and Significance: We conclude that the beneficial effect of curcumin during HFD consumption is mediated by attenuating lipogenic gene expression in the liver and the inflammatory response in the adipose tissue, in the absence o

The oxidative burst in tomato plants induced by race-specific elicitors of Cladosporium fulvum

grantor: University of TorontoOne of the intriguing features of plant disease resistance is an initial oxidative burst. The present study, using the 'Cladosporium fulvum '-tomato pathosystem, explored the oxidative burst in both leaf tissues and in cell cultures following treatment with race specific elicitors obtained from the fungus. The oxidative burst was detected by 2',7'dichlorofluorescin diacetate (DCFH-DA), a probe for detection of H2O2. A variety of tests, including the use of catalase, showed that the probe measured both intracellular and extracellular H2O2. Ile oxidative burst occurred within 1-2 hr in leaf tissues and within a few minutes in cell cultures, respectively, after elicitor treatment. In cell cultures, the oxidative burst was abolished by inhibitors of NADPH oxidase, suggesting that this enzyme is responsible for the generation of O2-, a precursor of H2O2. As well, O2- was detected 'in planta' by the Mn2+/diaminobenzidine technique. Prevention of increased cytosolic Ca2+ appeared to block the increased H2O2 generation. Studies with other inhibitors suggested that protein kinase(s) and phospholipase C were involved in the oxidative burst, supporting the possibility that the signaling mechanism leading to the oxidative burst in tomato cells is similar to that observed in neutrophils. Activities of antioxidant enzymes, e.g., superoxide dismutase, catalase, and glutathione 'S'-transferase, were not changed in leaves undergoing an oxidative burst. Total peroxidase activity, including ascorbate peroxidase, increased in elicitor-treated leaves but the activity of ascorbate peroxidase decreased by 4 hr. Elicitor-induced necrosis in leaves was significantly delayed, but not completely inhibited, by catalase or by scavengers of active oxygen species (AOS). An oxidative burst was still induced at elicitor dilutions which caused no visible necrosis and only high concentrations (ca 1M) of H2O2 could mimic the visible leaf necrosis induced by elicitor. Growth of 'C. fulvum' germ tubes was inhibited in vitro by moderate levels of H2O2, suggesting a possible role for H2O2 in restricting colonization. A model is proposed which describes the relationship between AOS, generated from an oxidative burst, and the fate of both host cells and invading fungal cells.Ph.D

The Adaptor Protein p66Shc Inhibits mTOR-Dependent Anabolic Metabolism

Adaptor proteins link surface receptors to intracellular signaling pathways and potentially control the way cells respond to nutrient availability. Mice deficient in p66Shc, the most recently evolved isoform of the Shc1 adaptor proteins and a mediator of receptor tyrosine kinase signaling, display resistance to diabetes and obesity. Using quantitative mass spectrometry, we found that p66Shc inhibited glucose metabolism. Depletion of p66Shc enhanced glycolysis and increased the allocation of glucose-derived carbon into anabolic metabolism, characteristics of a metabolic shift called the Warburg effect. This change in metabolism was mediated by the mammalian target of rapamycin (mTOR) because inhibition of mTOR with rapamycin reversed the glycolytic phenotype caused by p66Shc deficiency. Thus, unlike the other isoforms of Shc1, p66Shc appears to antagonize insulin and mTOR signaling, which limits glucose uptake and metabolism. Our results identify a critical inhibitory role for p66Shc in anabolic metabolism.National Institutes of Health (U.S.)United States. Dept. of DefenseW. M. Keck FoundationLAM FoundationNational Institutes of Health (U.S.) (Ruth L. Kirschstein National Research Service Award)National Institutes of Health (U.S.) (K99 Award

Genome-Wide Identification and Characterization of NAC Family in Hibiscus hamabo Sieb. et Zucc. under Various Abiotic Stresses

NAC transcription factor is one of the largest plant gene families, participating in the regulation of plant biological and abiotic stresses. In this study, 182 NAC proteins (HhNACs) were identified based on genomic datasets of Hibiscus hamabo Sieb. et Zucc (H. hamabo). These proteins were divided into 19 subfamilies based on their phylogenetic relationship, motif pattern, and gene structure analysis. Expression analysis with RNA-seq revealed that most HhNACs were expressed in response to drought and salt stress. Research of quantitative real-time PCR analysis of nine selected HhNACs supported the transcriptome data’s dependability and suggested that HhNAC54 was significantly upregulated under multiple abiotic stresses. Overexpression of HhNAC54 in Arabidopsis thaliana (A. thaliana) significantly increased its tolerance to salt. This study provides a basis for a comprehensive analysis of NAC transcription factor and insight into the abiotic stress response mechanism in H. hamabo

Curcumin does not stimulate the Wnt signaling pathway in mature adipocytes.

<p>(<b>A</b>) Samples from epididymal fat pad of the three groups of mice were prepared for Western blotting. β-cat and GSK-3 represent Wnt pathway effectors, while cyclin D1 and c-Myc are two known Wnt target genes. (<b>B</b>) Rat primary adipocytes were prepared and treated with insulin (100 nM), or curcumin (20 µM), or insulin plus curcumin for 0, 5, 30, and 60 min. Samples were collected for Western blotting, with indicated antibody. (<b>C</b>) Rat primary adipocytes were prepared and treated with 10 or 20 µM curcumin for 4 h, followed by Western blotting with indicated antibody. All panels show the representative blot (n = 3).</p