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Although macroautophagy/autophagy deficiency causes degenerative diseases, the deletion of essential autophagy genes in adipocytes paradoxically reduces body weight. Brown adipose tissue (BAT) plays an important role in body weight regulation and metabolic control. However, the key cellular mechanisms that maintain BAT function remain poorly understood. in this study, we showed that global or brown adipocyte-specific deletion of pink1, a Parkinson disease-related gene involved in selective mitochondrial autophagy (mitophagy), induced BAT dysfunction, and obesity-prone type in mice. Defective mitochondrial function is among the upstream signals that activate the NLRP3 inflammasome. NLRP3 was induced in brown adipocyte precursors (BAPs) from pink1 knockout (KO) mice. Unexpectedly, NLRP3 induction did not induce canonical inflammasome activity. Instead, NLRP3 induction led to the differentiation of pink1 KO BAPs into white-like adipocytes by increasing the expression of white adipocyte-specific genes and repressing the expression of brown adipocyte-specific genes. nlrp3 deletion in pink1 knockout mice reversed BAT dysfunction. Conversely, adipose tissue-specific atg7 KO mice showed significantly lower expression of Nlrp3 in their BAT. Overall, our data suggest that the role of mitophagy is different from general autophagy in regulating adipose tissue and whole-body energy metabolism. Our results uncovered a new mitochondria-NLRP3 pathway that induces BAT dysfunction. The ability of the nlrp3 knockouts to rescue BAT dysfunction suggests the transcriptional function of NLRP3 as an unexpected, but a quite specific therapeutic target for obesity-related metabolic diseases.Abbreviations: ACTB: actin, beta; BAPs: brown adipocyte precursors; BAT: brown adipose tissue; BMDMs: bone marrow-derived macrophages; CASP1: caspase 1; CEBPA: CCAAT/enhancer binding protein (C/EBP), alpha; ChIP: chromatin immunoprecipitation; EE: energy expenditure; HFD: high-fat diet; IL1B: interleukin 1 beta; ITT: insulin tolerance test; KO: knockout; LPS: lipopolysaccharide; NLRP3: NLR family, pyrin domain containing 3; PINK1: PTEN induced putative kinase 1; PRKN: parkin RBR E3 ubiquitin protein ligase; RD: regular diet; ROS: reactive oxygen species; RT: room temperature; UCP1: uncoupling protein 1 (mitochondrial, proton carrier); WT: wild-type.

BackgroundThe effectiveness of personal health records (PHRs) in diabetes management has already been verified in several clinical trials; however, evidence of their effectiveness in real-world scenarios is also necessary. To provide solid real-world evidence, an analysis that is more accurate than the analyses solely based on patient-generated health data should be conducted. ObjectiveThis study aimed to conduct a more accurate analysis of the effectiveness of using PHRs within electronic medical records (EMRs). The results of this study will provide precise real-world evidence of PHRs as a feasible diabetes management tool. MethodsWe collected log data of the sugar function in the My Chart in My Hand version 2.0 (MCMH 2.0) app from Asan Medical Center (AMC), Seoul, Republic of Korea, between December 2015 and April 2018. The EMR data of MCMH 2.0 users from AMC were collected and integrated with the PHR data. We classified users according to whether they were continuous app users. We analyzed and compared their characteristics, patterns of hemoglobin A1c (HbA1c) levels, and the proportion of successful HbA1c control. The following confounders were adjusted for HbA1c pattern analysis and HbA1c regulation proportion comparison: age, sex, first HbA1c measurement, diabetes complications severity index score, sugar function data generation weeks, HbA1c measurement weeks before MCMH 2.0 start, and generated sugar function data count. ResultsThe total number of MCMH 2.0 users was 64,932, with 7453 users having appropriate PHRs and diabetes criteria. The number of continuous and noncontinuous users was 133 and 7320, respectively. Compared with noncontinuous users, continuous users were younger (P

Aim: Patients with type 2 diabetes (T2DM) who require injectable therapy have been conventionally treated with insulin. A glucagon-like peptide 1 receptor agonist was recently recommended as first-line injectable treatment, but few studies have investigated the effects of switching from insulin to dulaglutide. This study investigated the clinical efficacy and parameters affecting responses to dulaglutide as an alternative to insulin in patients with T2DM in a real-world clinical setting.Methods: Ninety-eight patients with T2DM who were switched from insulin to dulaglutide therapy were retrospectively evaluated. Changes in HbA1c concentrations were assessed after 6 months of consistent treatment with dulaglutide. Multiple linear regression analysis was performed to evaluate parameters affecting the response to dulaglutide treatment.Results: After treatment with dulaglutide for 6 months, patients experienced changes in HbA1c of -0.95% (95% confidence interval [CI]: -1.30% to -0.59%, P < 0.001) and in body weight of -1.75 kg (95% CI: -2.42 to -1.08 kg, P < 0.001). Multiple linear regression analysis showed that higher baseline HbA1c was significantly associated with a greater reduction in HbA1c. The most frequent adverse events were gastrointestinal symptoms.Conclusion: Switching from insulin to dulaglutide can lead to significant improvement in HbA1c levels and body weight ​reduction in T2DM patients over 6 months. Higher baseline HbA1c is associated with a better clinical response to dulaglutide. [ABSTRACT FROM AUTHOR]