BackgroundNonalcoholic fatty liver disease is one of the most common liver diseases in the world and is a typical hepatic manifestation of metabolic syndrome which is characterized with lipid accumulation in liver. Nicotinamide phosphoribosyltransferase (NAMPT) has been recently identified as an enzyme involved in nicotinamide adenine dinucleotide (NAD+) biosynthesis and plays an important role in cellular metabolism in variety of organs in mammals. The aim of this study was to investigate the effects of NAMPT on high fat diet-induced hepatic steatosis.MethodsHepatic steatosis model was induced by high fat diet (HFD) in C57BL/6 mice in vivo. HepG2 and Hep1-6 hepatocytes were transfected with NAMPT vector plasmid or treated with NAMPT inhibitor FK866 and then incubated with oleic acid. Lipids accumulation was examined by HE staining or oil red staining. Quantitative RT-PCR and Western blot were used to measure expressions of the genes involved in lipogenic synthesis.ResultsFK866 significantly promoted liver steatosis in the mice fed with HFD and hepatic lipid accumulation in vitro, accompanied by the increases of the expressions of lipogenic genes such as sterol regulatory element-binding protein 1 (SREBP1) and fatty acid synthase (FASN). Nicotinamide mononucleotide (NMN) and NAD+ significantly rescued the actions of FK866 in vitro. In contrast, overexpression of NAMPT in HepG2 and Hep1-6 hepatocytes ameliorated hepatic lipid accumulation. In addition, FK866 decreased the protein levels of Sirt1 and phospho-AMPKα in liver of the HFD fed mice. Furthermore, Resveratrol, a Sirt1 activator, significantly reduced lipogenic gene expressions, while EX-527, a Sirt1 specific inhibitor, had the opposite effects.ConclusionOur results demonstrated that inhibition of NAMPT aggravated the HFD- or oleic acid-induced hepatic steatosis through suppressing Sirt1-mediated signaling pathway. On the one hand, the inhibition of NAMPT reduced the production of NAD+ through inhibiting the NAD+ salvage pathway, resulting in the decrease of Sirt1 activity, and then attenuated the deacetylation of SREBP1 in which the inhibition of SREBP1 activity promoted the expressions of FASN and ACC. On the other hand, the reduced Sirt1 activity alleviated the activation of AMPKα to further enhance SREBP1 activities.Electronic supplementary materialThe online version of this article (doi:10.1186/s12944-017-0464-z) contains supplementary material, which is available to authorized users.

It has been recently reported that CD38 was highly expressed in adipose tissues from obese people and CD38‐deficient mice were resistant to high‐fat diet (HFD)‐induced obesity. However, the role of CD38 in the regulation of adipogenesis and lipogenesis is unknown. In this study, to explore the roles of CD38 in adipogenesis and lipogenesis in vivo and in vitro, obesity models were generated with male CD38−/− and WT mice fed with HFD. The adipocyte differentiations were induced with MEFs from WT and CD38−/− mice, 3T3‐L1 and C3H10T1/2 cells in vitro. The lipid accumulations and the alternations of CD38 and the genes involved in adipogenesis and lipogenesis were determined with the adipose tissues from the HFD‐fed mice or the MEFs, 3T3‐L1 and C3H10T1/2 cells during induction of adipocyte differentiation. The results showed that CD38−/− male mice were significantly resistant to HFD‐induced obesity. CD38 expressions in adipocytes were significantly increased in WT mice fed with HFD, and the similar results were obtained from WT MEFs, 3T3‐L1 and C3H10T1/2 during induction of adipocyte differentiation. The expressions of PPARγ, AP2 and C/EBPα were markedly attenuated in adipocytes from HFD‐fed CD38−/− mice and CD38−/− MEFs at late stage of adipocyte differentiation. Moreover, the expressions of SREBP1 and FASN were also significantly decreased in CD38−/− MEFs. Finally, the CD38 deficiency‐mediated activations of Sirt1 signalling were up‐regulated or down‐regulated by resveratrol and nicotinamide, respectively. These results suggest that CD38 deficiency impairs adipogenesis and lipogenesis through activating Sirt1/PPARγ‐FASN signalling pathway during the development of obesity.

Background/Aims: Previous studies showed that CD38 deficiency protected heart from ischemia/reperfusion injury and high fat diet (HFD)-induced obesity in mice. However, the role of CD38 in HFD-induced heart injury remains unclear. In the present study, we have investigated the effects and mechanisms of CD38 deficiency on HFD-induced heart injury. Methods: The metabolites in heart from wild type (WT) and CD38 knockout (CD38^-/-) mice were examined using metabolomics analysis. Cell viability, lactate hydrogenase (LDH) release, super oxide dismutase (SOD) activity, reactive oxygen species (ROS) production, triglyceride concentration and gene expression were examined by biochemical analysis and QPCR. Results: Our results revealed that CD38 deficiency significantly elevated the intracellular glutathione (GSH) concentration and GSH/GSSG ratio, decreased the contents of free fatty acids and increased intracellular NAD⁺ level in heart from CD38^-/- mice fed with HFD. In addition, in vitro knockdown of CD38 significantly attenuated OA-induced cellular injury, ROS production and lipid synthesis. Furthermore, the expression of mitochondrial deacetylase Sirt3 as well as its target genes FOXO3 and SOD2 were markedly upregulated in the H9C2 cell lines after OA stimulation. In contrast, the expressions of NOX2 and NOX4 were significantly decreased in the cells after OA stimulation. Conclusion: Our results demonstrated that CD38 deficiency protected heart from HFD-induced oxidative stress via activating Sirt3/FOXO3-mediated anti-oxidative stress pathway.

A rat model of type II diabetic neuropathic pain can be established by feeding rats a high-fat, high-sugar diet for 8 weeks, in combination with intraperitoneal injection of 35 mg/kg STZ. This model can be stably maintained for at least 2 weeks.

Objective To evaluate the analgesic effectiveness of two novel regional nerve blocks in paediatric patients with developmental dysplasia of the hip (DDH) after open reduction surgeries. Design Prospective, double-blinded, randomised controlled trial. Setting 2 tertiary teaching hospitals in China between August 2017 and July 2018. Participants 110 paediatric patients aged 2–10 years with DDH undergoing open reduction surgeries were recruited, 95 were randomised and 90 were included in the final analysis. Interventions Random assignment to quadratus lumborum block III (QLB III) group, transversalis fascia plane block (TFPB) group and the control (no region nerve block) group. Primary and secondary outcome measures The primary outcome was the Face, Legs, Activity, Cry and Consolability (FLACC) Scale Scores. Secondary outcomes included perioperative opioid consumption, the time until first press of nurse-controlled analgesia/patient-controlled analgesia (NCA/PCA) pump and the total counts number of pressing, length of postanaesthesia care unit (PACU) stay, length of hospital stay, parental satisfaction with pain management and adverse events. Results Mean FLACC Scores were significantly lower in QLB III group and TFPB group while in the PACU and for 48 hours postoperatively, compared with control group (p<0.0001, p<0.0001, respectively). No differences were found for FLACC Scores between QLB III group and TFPB group, neither at rest (p=0.0402) nor while posture changing (p=0.0306). TFPB prolonged the first-time request for NCA/PCA analgesia, and decreased the total number of pressing counts, compared with QLB III (22.5 (16.2 to 28.7) vs 11.7 (6.6 to 16.8), p<0.0001; 2.4 (1.3 to 3.6) vs 3.8 (2.8 to 4.8), p=0.0111, respectively). No patient experienced any adverse events. Conclusions We suggested that both ultrasound-guided QLB III and TFPB should be considered as an option for perioperative analgesia in children with DDH undergoing open reduction surgeries. TFPB was superior to the QLB III because it prolonged the first-time request for NCA/PCA analgesia and decreased the total counts number of pressing. Trial registration number NCT03189966/2017.