High Endogenously Synthesized N-3 Polyunsaturated Fatty Acids in Fat-1 Mice Attenuate High-Fat Diet-Induced Insulin Resistance by Inhibiting NLRP3 Inflammasome Activation via Akt/GSK-3ß/TXNIP Pathway.

High-fat (HF) diets and low-grade chronic inflammation contribute to the development of insulin resistance and type 2 diabetes (T2D), whereas n-3 polyunsaturated fatty acids (PUFAs), due to their anti-inflammatory effects, protect against insulin resistance. Interleukin (IL)-1ß is implicated in insulin resistance, yet how n-3 PUFAs modulate IL-1ß secretion and attenuate HF diet-induced insulin resistance remains elusive. In this study, a HF diet activated NLRP3 inflammasome via inducing reactive oxygen species (ROS) generation and promoted IL-1ß production primarily from adipose tissue preadipocytes, but not from adipocytes and induced insulin resistance in wild type (WT) mice. Interestingly, endogenous synthesized n-3 polyunsaturated fatty acids (PUFAs) reversed this process in HF diet-fed fat-1 transgenic mice although the HF diet induced higher weight gain in fat-1 mice, compared with the control diet. Mechanistically, palmitic acid (PA), the main saturated fatty acid in an HF diet inactivated AMPK and led to decreased GSK-3ß phosphorylation, at least partially through reducing Akt activity, which ultimately blocked the Nrf2/Trx1 antioxidant pathway and induced TXNIP cytoplasm translocation and NLRP3 inflammasome activation, whereas docosahexaenoic acid (DHA), the most abundant n-3 PUFA in fat-1 adipose tissue, reversed this process via inducing Akt activation. Our GSK-3ß shRNA knockdown study further revealed that GSK-3ß played a pivot role between the upstream AMPK/Akt pathway and downstream Nrf2/Trx1/TXNIP pathway. Given that NLRP3 inflammasome is implicated in the development of most inflammatory diseases, our results suggest the potential of n-3 PUFAs in the prevention or adjuvant treatment of NLRP3 inflammasome-driven diseases.

The role of uric acid in the pathogenesis of diabetic retinopathy based on Notch pathway.

OBJECTIVE: Uric acid has been proposed as an independent risk factor of diabetic retinopathy. Although Notch signaling was reported to be affected in the presence of high concentrations of uric acid or glucose, the underlying mechanisms of hyperuricemia through the Notch signaling pathway to promote the development of diabetic retinopathy remain unknown. METHODS: We incubated human retinal endothelial cells (HRECs) with high glucose, high uric acid and high glucose plus high glucose respectively and evaluated the apoptosis rate in different treated cells by Tunel staining. We induced diabetic model by intraperitoneally streptozotocin. Then healthy rats and diabetic rats were given with adenine and oteracil potassium by gavage. Using automatic biochemical analyzer to detect blood glucose, uric acid, urea nitrogen, creatinine levels, to verify the success of modeling. The expression and mRNA levels of ICAM-1, IL-6, MCP-1, TNF-a, receptors Notch 1, ligands Dll 1, Dll 4, Jagged 1, Jagged 2 were detected by RT-PCR and Western-Blot. Notch1 siRNA was used to interfere Notch signaling pathway, the expression and mRNA levels of ICAM-1, IL-6, MCP-1 and TNF-α was detected by RT-PCR and Western blot respectively. RESULTS: In vitro models, the apoptosis of HRECs cells in high uric acid plus high glucose group was the most significant. In vitro and vivo models, detection of inflammatory cytokines revealed that the expression of inflammatory cytokines increased most significantly in high uric acid plus high glucose group. Notch signaling pathway activity was also increased most significantly in high uric acid plus high glucose group. After Notch 1 siRNA transfection in high glucose and high glucose plus uric acid group, the activity of Notch signaling pathway was successfully down-regulated. We found that the apoptosis of HRECs was significantly decreased in cells transfected with Notch 1 siRNA compared to the blank vector group, and the expression of inflammatory cytokines in cells was also significantly decreased. CONCLUSION: Our study reported that high uric acid can promote the inflammation of the retina and increase the activity of Notch signaling pathway on the basis of high glucose. Hyperuricemia promotes the development of diabetic retinopathy by increasing the activity of Notch signaling pathway. Notch signaling pathway is a potential therapeutic target for diabetic retinopathy.

[Effects of continuous positive airway pressure upon the un-treatment hour changes of blood glucose level in patients with obstructive sleep apnea hypopnea syndrome and type 2 diabetes].

OBJECTIVE: To assess the effects of short-term continuous positive airway pressure (CPAP) upon un-treatment hour glucose control via a continuous glucose monitoring system (CGMS) in patients with obstructive sleep apnea hypopnea syndrome and type 2 diabetes (OWD). METHODS: A total of 23 case of hospitalized OWD were recruited. CGMS was applied for 2 days before and 4 days during CPAP treatment. The treatment hour (6 h, 0:00 - 6:00) and un-treatment hour (14 h, 6:00 - 22:00) glucose level and glucose variability were analyzed. Insulin resistance was assessed with fasting plasma blood glucose (FPG), plasma insulin (FINS) and homeostatic model assessment of insulin resistance index (HOMA-IR). RESULTS: The short-term CPAP treatment corrected sleep-disordered breathing and induced significant decreases of treatment and un-treatment hour glucose level ((7.07 ± 2.02) mmol/L vs (6.34 ± 1.57) mmol/L, (8.04 ± 1.99) mmol/L vs (7.64 ± 1.81) mmol/L, both P < 0.05). Glucose variability of treatment and un-treatment hours significantly decreased after CPAP treatment (0.41 ± 0.24 vs 0.29 ± 0.18, 1.02 ± 0.50 vs 0.78 ± 0.45, all P < 0.05). Short-term treatment also induced an increase of insulin sensitivity, as indicated by a significant decrease of HOMA-IR (4.02 ± 2.07 vs 3.08 ± 1.58, P < 0.05). CONCLUSION: Short-term CPAP treatment in OWD may improve not only insulin resistance but also blood glucose and glucose variability during treatment and un-treatment hours.

[Study on the chemical constituents of Phellinus lonicerinus].

OBJECTIVE: To study the chemical constituents of Phellinus lonicerinus. METHODS: The constituents were seperated and purified by silica column chromatography, Sephadex LH-20 and other column chromatography, then their structures were identified by spectral methods. RESULTS: Six compounds were isolated and identified as ergosta-6,22-dien-3beta, 5beta, 8beta-triol (1), erogosterol (2), vanillin (3), 3,4-dihydroxy benzalacetone (4), beta-sitosterol (5), docosanoic acid (6). CONCLUSION: All compounds are isolated from Phellinus lonicerinus for the first time and compound 4 isa new natural product.