Identification of distinct immune infiltration and potential biomarkers in patients with liver ischemia-reperfusion injury.

AIMS: To identify alterations of specific gene expression, immune infiltration components, and potential biomarkers in liver ischemia-reperfusion injury (IRI) following liver transplantation (LT). MATERIALS AND METHODS: GSE23649 and GSE151648 datasets were obtained from the Gene Expression Omnibus (GEO) database. To determine the differentially expressed genes (DEGs), we utilized the R package "limma". We also identify the infiltration of different immune cells through single-sample gene-set enrichment analysis (ssGSEA). Furthermore, we utilized LASSO logistic regression to select feature genes and Spearman's rank correlation analysis to determine the correlation between these genes and infiltrating immune cells. Finally, the significance of these feature genes was confirmed using a mouse model of hepatic IRI. KEY FINDINGS: A total of 17 DEGs were acquired, most of which were associated with inflammation, apoptosis, cell proliferation, immune disorders, and cellular response. 28 immune cell types were determined using ssGSEA. 5 feature genes (ADM, KLF6, SERPINE1, SLC20A1, and HBB) were screened using LASSO analysis, but the HBB gene was ultimately excluded due to the lack of statistical significance in the GSE151648 dataset. These 4 feature genes were predominantly related to immune cells. Finally, 15 significantly distinctive types of immune cells between the control and IRI groups were verified. SIGNIFICANCE: We unveiled that macrophages, dendritic cells (DCs), neutrophils, CD4 T cells, and other immune cells infiltrated the IRI that occurred after LT. Moreover, we identified ADM, KLF6, SERPINE1, and SLC20A1 as potential biological biomarkers underlying IRI post-transplant, which may improve the diagnosis and prognosis of this condition.

Characteristics of mesenteric adipose tissue attached to different intestinal segments and their roles in immune regulation.

Mesenteric adipose tissue (MAT) plays a critical role in the intestinal physiological ecosystems. Small and large intestines have evidently intrinsic and distinct characteristics. However, whether there exist any mesenteric differences adjacent to the small and large intestines (SMAT and LMAT) has not been properly characterized. We studied the important facets of these differences, such as morphology, gene expression, cell components, and immune regulation of MATs, to characterize the mesenteric differences. The SMAT and LMAT of mice were used for comparison of tissue morphology. Paired mesenteric samples were analyzed by RNA-seq to clarify gene expression profiles. MAT partial excision models were constructed to illustrate the immune regulation roles of MATs, and 16S-seq was applied to detect the subsequent effect on microbiota. Our data show that different segments of mesenteries have different morphological structures. SMAT not only has smaller adipocytes but also contains more fat-associated lymphoid clusters than LMAT. The gene expression profile is also discrepant between these two MATs in mice. B-cell markers were abundantly expressed in SMAT, whereas development-related genes were highly expressed in LMAT. Adipose-derived stem cells of LMAT exhibited higher adipogenic potential and lower proliferation rates than those of SMAT. In addition, SMAT and LMAT play different roles in immune regulation and subsequently affect microbiota components. Finally, our data clarified the described differences between SMAT and LMAT in humans. There were significant differences in cell morphology, gene expression profiles, cell components, biological characteristics, and immune and microbiota regulation roles between regional MATs.NEW & NOTEWORTHY Our results change the paradigm of how we regard MAT as a contiguous and homogeneous tissue to an intensely heterogeneous tissue. Appreciation of the differences between regional MATs will guide future research to investigate the specialized roles of different MATs in intestinal health and disease.

Increased Energy Expenditure and Energy Loss Through Feces Contribute to the Long-Term Outcome of Roux-en-Y Gastric Bypass in a Diet-Induced Obese Mouse Model.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) has been proved to be more effective than other bariatric procedures in the long term on body-weight loss and remission of diabetes. However, the mechanism remains poorly understood. Long-term changes in energy metabolism after RYGB have rarely been reported. OBJECTIVE: To investigate the long-term effects of RYGB on energy metabolism on a diet-induced obesity (DIO) mouse model. METHODS: DIO mice fed a high-fat diet were assigned to two groups: RYGB (n=8) and sham (n=7), followed by high-fat diet feeding until 12 weeks after surgery. Body weight and food intake were recorded weekly. Measurement of body composition and energy metabolism by metabolic chamber were conducted at weeks 4, 8, and 12 after surgery. Fecal energy measurement, intraperitoneal glucose-tolerance tests, and insulin-tolerance tests were conducted at postoperative week 12. RESULTS: Food intake was reduced in the RYGB group within the first 3 weeks after surgery and increased to the same as the sham group from postoperative week 4. At 12 weeks after surgery, body weight had reduced by 36%±3.2% in the RYGB group compared to a 16%±2% body-weight gain in the sham group, while fat mass had reduced significantly in the RYGB group compared to the sham group (9.2%±1.5% versus 30.1%±0.7%). Energy expenditure was significantly higher at postoperative week 8 in the RYGB group than the sham group. In comparison with the sham group, the respiratory exchange ratio was unchanged, decreased, and increased in the RYGB group at postoperative weeks 4, 8, and 12, respectively. Fecal energy measurement showed that feces from mice in the RYGB group contained higher energy levels than the sham group. Glucose metabolism had significantly improved in the RYGB group, in contrast to the sham group, demonstrated by intraperitoneal glucose tolerance tests (AUC 1,502±104 versus 2,277±198, respectively) and insulin tolerance tests (AUC 524±50 versus 838±63, respectively). CONCLUSION: Increased energy expenditure and energy loss through feces contribute to long-term body-weight control after RYGB. Enhanced glucose utilization might play a role in long-term improvement in glucose metabolism.