TRAF3IP2 (TRAF3 Interacting Protein 2) Mediates Obesity-Associated Vascular Insulin Resistance and Dysfunction in Male Mice

Insulin resistance in the vasculature is a characteristic feature of obesity and contributes to the pathogenesis of vascular dysfunction and disease. However, the molecular mechanisms underlying obesity-associated vascular insulin resistance and dysfunction remain poorly understood. We hypothesized that TRAF3IP2 (TRAF3 interacting protein 2), a proinflammatory adaptor molecule known to activate pathological stress pathways and implicated in cardiovascular diseases, plays a causal role in obesity-associated vascular insulin resistance and dysfunction. We tested this hypothesis by employing genetic-manipulation in endothelial cells in vitro, in isolated arteries ex vivo, and diet-induced obesity in a mouse model of TRAF3IP2 ablation in vivo. We show that ectopic expression of TRAF3IP2 blunts insulin signaling in endothelial cells and diminishes endothelium-dependent vasorelaxation in isolated aortic rings. Further, 16 weeks of high fat/high sucrose feeding impaired glucose tolerance, aortic insulin-induced vasorelaxation, and hindlimb postocclusive reactive hyperemia, while increasing blood pressure and arterial stiffness in wild-type male mice. Notably, TRAF3IP2 ablation protected mice from such high fat/high sucrose feeding-induced metabolic and vascular defects. Interestingly, wild-type female mice expressed markedly reduced levels of TRAF3IP2 mRNA independent of diet and were protected against high fat/high sucrose diet-induced vascular dysfunction. These data indicate that TRAF3IP2 plays a causal role in vascular insulin resistance and dysfunction. Specifically, the present findings highlight a sexual dimorphic role of TRAF3IP2 in vascular control and identify it as a promising therapeutic target in vasculometabolic derangements associated with obesity, particularly in males.

S-Nitrosoglutathione Reverts Dietary Sucrose-Induced Insulin Resistance

The liver is a fundamental organ to ensure whole-body homeostasis, allowing for a proper increase in insulin sensitivity from the fast to the postprandial status. Hepatic regulation of glucose metabolism is crucial and has been shown to be modulated by glutathione (GSH) and nitric oxide (NO). However, knowledge of the metabolic action of GSH and NO in glucose homeostasis remains incomplete. The current study was designed to test the hypothesis that treatment with S-nitrosoglutathione is sufficient to revert insulin resistance induced by a high-sucrose diet. Male Wistar rats were divided in a control or high-sucrose group. Insulin sensitivity was determined: (i) in the fast state; (ii) after a standardized test meal; (iii) after GSH + NO; and after (iv) S-nitrosoglutathione (GSNO) administration. The fasting glucose level was not different between the control and high-sucrose group. In the liver, the high-sucrose model shows increased NO and unchanged GSH levels. In control animals, insulin sensitivity increased after a meal or administration of GSH+NO/GSNO, but this was abrogated by sucrose feeding. GSNO was able to revert insulin resistance induced by sucrose feeding, in a dose-dependent manner, suggesting that they have an insulin-sensitizing effect in vivo. These effects are associated with an increased insulin receptor and Akt phosphorylation in muscle cells. Our findings demonstrate that GSNO promotes insulin sensitivity in a sucrose-induced insulin-resistant animal model and further implicates that this antioxidant molecule may act as a potential pharmacological tool for the treatment of insulin resistance in obesity and type 2 diabetes.

Internal ammonium excess induces ROS-mediated reaction and causes carbon scarcity in rice

Background: Overuse of nitrogen fertilizers is often applied to satisfy strong nitrogen demand of high–yielding rice, leading to persistent NH4+ excess in the plant. However, the mechanisms constraining the effectiveness of elevated plant NH4+ in plant growth and grain yield of rice are not sufficiently addressed. The current study analyses the early performance of such internal NH4+ excess in rice, aiming at finding out constraints against compromised nitrogen use efficiency Results: By mimicking a rapid accumulation of plant NH4+ and an RNA-Seq analysis, the present work reveals that internal NH4+ excess in rice plant initiates a burst of reactive oxygen species (ROS) and triggers probably specifically the activation of glutathione transferase (GST)–mediated glutathione cycling for ROS cleavage. Meanwhile, the suppression of the expression of genes involved in photon caption and the activity of primary CO2 fixation enzymes (Rubisco), provides implications of a reduction in photosynthetic carbon income.Along the progress of NH4+/ROS stresses, enhanced energy–producing processes (carbon breakdown) take place as indicated by strong induction of glycolysis related genes to meet the demand of energy consuming activation of ROS–cleavaging systems. The development of these defensive reactions causes a sugar scarcity in the plant that accumulatively leads to growth inhibition. To the opposite direction, a sucrose feeding treatment to the roots renders the accumulation of free NH4+ and ROS, partly restores the activities of photosynthetic CO2 fixation and thus alleviates the scarcity in active carbon source. Conclusion: Our results indicate that carbon scarcity is probably a major constraint in rice plant that limits the performance of nitrogen under overuse of N fertilizers. Keywords: rice, NH4+ excess, ROS, GSH cycle, carbon scarcity, sucrose feeding.

Sucrose promotes etiolated stem branching through activation of cytokinin accumulation followed by vacuolar invertase activity

ABSTRACTThe potato (Solanum tuberosum L.) tuber is a swollen stem. Sprouts growing from the tuber nodes represent dormancy release and loss of apical dominance. We recently identified sucrose as a key player in triggering potato stem branching. To decipher the mechanisms by which sucrose induces stem branching, we investigated the nature of the inducing molecule and the involvement of vacuolar invertase (VInv) and the plant hormone cytokinin (CK) in this process. Sucrose was more efficient at enhancing lateral bud burst and elongation than either of its hexose moieties (glucose and fructose), or a slowly metabolizable analog of sucrose (palatinose). Sucrose feeding induced expression of the sucrose transporter gene SUT2, followed by enhanced expression and activity of VInv in the lateral bud prior to its burst. We observed a reduction in the number of branches on stems of VInv-RNA interference lines during sucrose feeding, suggesting that sucrose breakdown is needed for lateral bud burst. Sucrose feeding led to increased CK content in the lateral bud base prior to bud burst. Inhibition of CK synthesis or perception inhibited the sucrose-induced bud burst, suggesting that sucrose induces stem branching through CK. Together, our results indicate that sucrose is transported to the bud, where it promotes bud burst by inducing CK accumulation and VInv activity.

Internal ammonium excess induces ROS-mediated reaction and causes carbon scarcity in rice

Background: Overuse of nitrogen fertilizers is often applied to satisfy strong nitrogen demand of high-yielding rice, leading to persistent NH 4 + excess in the plant. However, the mechanisms constraining the effectiveness of elevated plant NH 4 + in plant growth and grain yield of rice are not sufficiently addressed. In the current study, we attempt to real the nature or mode-of-action of such internal NH 4 + excess in rice, and the efficient coordination measure with current high N fertilizer cropping systems is investigated. Results: By mimicking a rapid accumulation of plant NH 4 + and an RNA-Seq analysis, the present work reveals that internal NH 4 + excess in rice plant initiates a burst of reactive oxygen species (ROS) and triggers probably specifically the activation of glutathione transferase (GST)-mediated glutathione cycling for ROS cleavage. Meanwhile, the suppression of the expression of genes involved in photon caption and the activity of primary CO 2 fixation enzymes (Rubisco), provides implications of a reduction in photosynthetic carbon income. Along the progress of NH 4 + / ROS stresses, enhanced energy-producing processes (carbon breakdown) take place as indicated by strong induction of glycolysis related genes to meet the demand of energy consuming activation of ROS-cleavaging systems. The development of these defensive reactions causes a sugar scarcity in the plant that accumulatively leads to growth inhibition. To the opposite direction, a sucrose feeding treatment to the roots renders the accumulation of free NH 4 + and ROS, partly restores the activities of photosynthetic CO 2 fixation and thus alleviates the scarcity in active carbon source. Conclusion: Our results demonstrate the necessity of efficient carbon coordination, aiming at improving the nitrogen performances under current N fertilizer overuse circumstances.