Mild alkali-pretreatment effectively extracts guaiacyl-rich lignin for high lignocellulose digestibility coupled with largely diminishing yeast fermentation inhibitors in Miscanthus.

In this study, various alkali-pretreated lignocellulose enzymatic hydrolyses were evaluated by using three standard pairs of Miscanthus accessions that showed three distinct monolignol (G, S, H) compositions. Mfl26 samples with elevated G-levels exhibited significantly increased hexose yields of up to 1.61-fold compared to paired samples derived from enzymatic hydrolysis, whereas Msa29 samples with high H-levels displayed increased hexose yields of only up to 1.32-fold. In contrast, Mfl30 samples with elevated S-levels showed reduced hexose yields compared to the paired sample of 0.89-0.98 folds at p<0.01. Notably, only the G-rich biomass samples exhibited complete enzymatic hydrolysis under 4% NaOH pretreatment. Furthermore, the G-rich samples showed more effective extraction of lignin-hemicellulose complexes than the S- and H-rich samples upon NaOH pretreatment, resulting in large removal of lignin inhibitors to yeast fermentation. Therefore, this study proposes an optimal approach for minor genetic lignin modification towards cost-effective biomass process in Miscanthus.

Interferon regulatory factor 7 deficiency prevents diet-induced obesity and insulin resistance.

Obesity-related inflammation has been implicated in the pathogenesis of insulin resistance and type 2 diabetes. In this study, we addressed the potential role of interferon regulatory factor 7 (IRF7), a master regulator of type I interferon-dependent immune responses, in the regulation of energy metabolism. The expression levels of IRF7 were increased in white adipose tissue, liver tissue, and gastrocnemius muscle of both diet-induced obese mice and ob/ob mice compared with their lean counterparts. After feeding a high-fat diet (HFD) for 24 wk, IRF7 knockout (KO) mice showed less weight gain and adiposity than wild-type controls. KO of IRF7 improved glucose and lipid homeostasis and insulin sensitivity. Additionally, KO of IRF7 ameliorated diet-induced hepatic steatosis. Next, we assessed the inflammatory state of the IRF7 KO mice on the HFD. These mice showed less macrophage infiltration into multiple organs and were protected from local and systemic inflammation. This study demonstrates a role for IRF7 in diet-induced alterations in energy metabolism and insulin sensitivity. Our results also suggest that IRF7 is involved in the etiology of metabolic abnormalities, which suggests a new strategy for treating obesity and type 2 diabetes.

Interferon regulatory factor 9 protects against hepatic insulin resistance and steatosis in male mice.

UNLABELLED: Obesity is a calorie-excessive state associated with high risk of diabetes, atherosclerosis, and certain types of tumors. Obesity may induce inflammation and insulin resistance (IR). We found that the expression of interferon (IFN) regulatory factor 9 (IRF9), a major transcription factor mediating IFN responses, was lower in livers of obese mice than in those of their lean counterparts. Furthermore, whole-body IRF9 knockout (KO) mice were more obese and had aggravated IR, hepatic steatosis, and inflammation after chronic high-fat diet feeding. In contrast, adenoviral-mediated hepatic IRF9 overexpression in both diet-induced and genetically (ob/ob) obese mice showed markedly improved hepatic insulin sensitivity and attenuated hepatic steatosis and inflammation. We further employed a yeast two-hybrid screening system to investigate the interactions between IRF9 and its cofactors. Importantly, we identified that IRF9 interacts with peroxisome proliferator-activated receptor alpha (PPAR-α), an important metabolism-associated nuclear receptor, to activate PPAR-α target genes. In addition, liver-specific PPAR-α overexpression rescued insulin sensitivity and ameliorated hepatic steatosis and inflammation in IRF9 KO mice. CONCLUSION: IRF9 attenuates hepatic IR, steatosis, and inflammation through interaction with PPAR-α.

Three lignocellulose features that distinctively affect biomass enzymatic digestibility under NaOH and H2SO4 pretreatments in Miscanthus.

In this study, total 80 typical Miscanthus accessions were examined with diverse lignocellulose features, including cellulose crystallinity (CrI), degree of polymerization (DP), and mole number (MN). Correlation analysis revealed that the crude cellulose CrI and MN, as well as crystalline cellulose DP, displayed significantly negative influence on biomass enzymatic digestibility under pretreatments with NaOH or H(2)SO(4) at three concentrations. By contrast, the comparative analysis of two Miscanthus samples with similar cellulose contents showed that crude cellulose DP and crystalline cellulose MN were positive factors on biomass saccharification, indicating cross effects among the cellulose levels and the three cellulose features. The results can provide insights into mechanism of the lignocellulose enzymatic digestion, and also suggest potential approaches for genetic engineering of bioenergy crops.

CARD3 deficiency exacerbates diet-induced obesity, hepatosteatosis, and insulin resistance in male mice.

Caspase activation and recruitment domain 3 (CARD3) is a 61-kDa protein kinase with an N-terminal serine/threonine kinase domain and a C-terminal CARD. Previous research on the function of CARD3 has focused on its role in the immune response and inflammatory diseases. Obesity is now a worldwide health problem and is generally recognized as an inflammatory disease. Unexpectedly, we found that CARD3 expression was lower during obesity. In this study, we explored the biological and genetic bases of obesity using CARD3-knockout (KO) and wild-type (WT) mice fed a high-fat diet (HFD) for 24 weeks. We demonstrate that KO mice were more obese than their WT littermates, and KO mice exhibited obvious visceral fat accumulation and liver weight gains after 24 weeks of HFD feeding. We also observed more severe hepatosteatosis in KO mice compared with the WT controls. Hepatic steatosis in the HFD-fed KO mice was linked to a significant increase in the expression of key lipogenic and cholesterol synthesis enzymes, whereas the expression of the enzymes involves in ß-oxidation was dramatically reduced. Furthermore, we confirmed the repression of AMP-activated protein kinase signaling and activation of the endoplasmic reticulum stress response. Fatty liver impaired the global glucose and lipid metabolism, which further exacerbated the insulin resistance associated with the repression of Akt signaling and up-regulated systemic inflammation through the M1/M2 (pro- and anti-inflammation) type switch and the activation of the nuclear factor-κB pathway. Our studies demonstrate the crucial role of CARD3 in metabolism and indicate that CARD3 deficiency promotes the diet-induced phenotype of type 2 diabetes.