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

Characterization of a Novel Plant Promoter Specifically Induced by Heavy Metal and Identification of the Promoter Regions Conferring Heavy Metal Responsiveness

The bean (Phaseolus vulgaris) stress-related gene number 2 (PvSR2) gene responds to heavy metals but not to other forms of environmental stresses. To elucidate its heavy metal-regulatory mechanism at the transcriptional level, we isolated and characterized the promoter region (−1623/+48) of PvSR2. Deletions from the 5′ end revealed that a sequence between −222 and −147 relative to the transcriptional start site was sufficient for heavy metal-specific induction of the promoter region of PvSR2. Detailed analysis of this 76-bp fragment indicated that heavy metal-responsive elements were localized in two regions (−222/−188 and −187/−147), each of which could separately confer heavy metal-responsive expression on the β-glucuronidase gene in the context of a minimal cauliflower mosaic virus 35S promoter. Region I (−222/−188) contains a motif (metal-regulatory element-like sequence) similar to the consensus metal-regulatory element of the animal metallothionein gene, and mutation of this motif eliminated the heavy metal-inducible function of region I. Region II (−187/−147) had no similarity to previously identified cis-acting elements involved in heavy metal induction, suggesting the presence of a novel heavy metal-responsive element. Transformed tobacco (Nicotiana tabacum) seedlings expressing β-glucuronidase under control of the PvSR2 promoter region (−687/+48) showed heavy metal-specific responsive activity that depended on the type and concentration of the heavy metal and the type of organ. These findings further our understanding of the regulation of PvSR2 expression and provide a new heavy-metal-inducible promoter system in transgenic plants

MTP8 from <i>Triticum urartu</i> Is Primarily Responsible for Manganese Tolerance

Mineral nutrients, such as manganese (Mn) and iron (Fe), play essential roles in many biological processes in plants but their over-enrichment is harmful for the metabolism. Metal tolerance proteins (MTPs) are involved in cellular Mn and Fe homeostasis. However, the transporter responsible for the transport of Mn in wheat is unknown. In our study, TuMTP8, a Mn-CDF transporter from diploid wheat (Triticum urartu), was identified. Expression of TuMTP8 in yeast strains of Δccc1 and Δsmf1 and Arabidopsis conferred tolerance to elevated Mn and Fe, but not to other metals (zinc, cobalt, copper, nickel, or cadmium). Compared with TuVIT1 (vacuole Fe transporter), TuMTP8 shows a significantly higher proportion in Mn transport and a smaller proportion in Fe transport. The transient analysis in tobacco epidermal cells revealed that TuMTP8 localizes to vacuolar membrane. The highest transcript levels of TuMTP8 were in the sheath of the oldest leaf and the awn, suggesting that TuMTP8 sequesters excess Mn into the vacuole in these organs, away from more sensitive tissues. These findings indicate that TuMTP8, a tonoplast-localized Mn/Fe transporter, functions as a primary balancer to regulate Mn distribution in T. urartu under elevated Mn conditions and participates in the intracellular transport and storage of excess Mn as a detoxification mechanism, thereby conferring Mn tolerance

A repeat region from the Brassica juncea HMA4 gene BjHMA4R is specifically involved in Cd2+ binding in the cytosol under low heavy metal concentrations

Abstract Background HMA4 transporters are involved in the transport and binding of divalent heavy metals (Cd, Zn, Pb [lead] and Co [cobalt]). In general, as efflux pumps, HMA4 transporters can increase the heavy metal tolerance of yeast and Escherichia coli. Additional research has shown that the C-terminus of HMA4 contains a heavy metal-binding domain and that heterologous expression of a portion of peptides from this C-terminal domain in yeast provides a high level of Cd tolerance and Cd hyperaccumulation. Results We cloned BjHMA4 from Brassica juncea, and quantitative real-time PCR analysis revealed that BjHMA4 was upregulated by Zn and Cd in the roots, stems and leaves. Overexpression of BjHMA4 dramatically affects Zn/Cd distribution in rice and wheat seedlings. Interestingly, BjHMA4 contains a repeat region named BjHMA4R within the C-terminal region; this repeat region is not far from the last transmembrane domain. We further characterized the detailed function of BjHMA4R via yeast and E. coli experiments. Notably, BjHMA4R greatly and specifically improved Cd tolerance, and BjHMA4R transformants both grew on solid media that contained 500 μM CdCl2 and presented improved Cd accumulation (approximately twice that of wild-type [WT] strains). Additionally, visualization via fluorescence microscopy indicated that BjHMA4R clearly localizes in the cytosol of yeast. Overall, these findings suggest that BjHMA4R specifically improves Cd tolerance and Cd accumulation in yeast by specifically binding Cd2+ in the cytosol under low heavy metal concentrations. Moreover, similar results in E. coli experiments corroborate this postulation. Conclusion BjHMA4R can specifically bind Cd2+ in the cytosol, thereby substantially and specifically improving Cd tolerance and accumulation under low heavy metal concentrations

A Study on Tissue-Specific Metabolite Variations in Polygonum cuspidatum by High-Resolution Mass Spectrometry-Based Metabolic Profiling

Polygonum cuspidatum Sieb. et Zucc. is a traditional Chinese herbal medicine widely used to treat tussis, hepatitis and arthralgia. This study identified and quantitatively described the bioactive compounds in different P. cuspidatum tissues. Metabolic profiles of root, stem, leaf, flower, rhizome and seed were determined using high-resolution mass spectrometry in combination with multivariate analyses. In total, 53 metabolites, 8 reported for the first time in this species, were putatively identified and classified mainly as stilbenes, anthraquinones and flavonoids. A principal component analysis, cluster analysis and heatmap were used to depict the correlations between specimens and the relative abundance levels of these compounds in different plant tissues. An orthogonal partial least square discriminant analysis found that 13 metabolites showed distinct differences among the six plant tissues, making them potential discriminative tissue-identification markers. This study will provide guidance in comparing, selecting and exploiting the medicinal uses of different P. cuspidatum tissues

PcWRKY11, an II-d WRKY Transcription Factor from Polygonum cuspidatum, Enhances Salt Tolerance in Transgenic Arabidopsis thaliana

Being an invasive plant, Polygonum cuspidatum is highly resilient and can survive in unfavorable environments for long periods; however, its molecular mechanisms associated with such environmental resistance are largely unknown. In this study, a WRKY transcription factor (TF) gene, PcWRKY11, was identified from P. cuspidatum by analyzing methyl jasmonate (MeJA)-treated transcriptome data. It showed a high degree of homology with WRKY11 from Arabidopsis thaliana, containing a WRKY domain and a zinc finger structure and II-d WRKY characteristic domains of HARF, a calmodulin-binding domain (C-motif), and a putative nuclear localization signal (NLS) through sequence alignment and functional element mining. qPCR analysis showed that the expression of PcWRKY11 can be induced by NaCl, osmotic stress, and UV-C. In this study, we also found that overexpression of PcWRKY11 in A. thaliana could significantly increase salt tolerance. To explore its possible molecular mechanism, further investigations showed that compared with the wild type (WT), under salt stress, the transgenic plants showed a lower malondialdehyde (MDA) content, higher expression of ascorbate peroxidase (APX) and superoxide dismutase (SOD), and higher enzyme activity of peroxidase (POD), superoxide dismutase (SOD), and catalase (CAT). Moreover, the transgenic plants also showed higher expression of &Delta;1-pyrroline-5-carboxylate synthase (AtP5CS), and higher contents of proline and soluble sugar. Taken together, these results indicate that PcWRKY11 may have a positive role in plants&rsquo; adaptation to salinity conditions by reducing reactive oxygen species (ROS) levels and increasing osmosis substance synthesis