Interventional metabology: A review of bariatric arterial embolization and endovascular denervation for treating metabolic disorders.

The rising prevalence of metabolic disorders such as obesity and type 2 diabetes mellitus (T2DM) poses a major challenge to global health. Existing therapeutic approaches have limitations, and there is a need for new, safe, and less invasive treatments. Interventional metabolic therapy is a new addition to the treatment arsenal for metabolic disorders. This review focuses on two interventional techniques: bariatric arterial embolization (BAE) and endovascular denervation (EDN). BAE involves embolizing specific arteries feeding ghrelin-producing cells to suppress appetite and promote weight loss. EDN targets nerves that regulate metabolic organs to improve glycemic control in T2DM patients. We describe the current state of these techniques, their mechanisms of action, and the available safety and effectiveness data. We also propose a new territory called "Interventional Metabology" to encompass these and other interventional approaches to treating metabolic disorders.

Heat shock protein 90 inhibitor ameliorates pancreatic fibrosis by degradation of transforming growth factor-ß receptor.

BACKGROUND AND AIM: Pancreatic fibrosis increases pancreatic cancer risk in chronic pancreatitis (CP). Pancreatic stellate cells (PSCs) play a critical role in pancreatic fibrosis by transforming growth factor-ß (TGFß) has been shown to inhibit transforming growth factor-ß receptor (TGFßR)-mediated Smad and no-Smad signaling pathways. Thus, the effects of Hsp90 inhibitor on pancreatic fibrosis are evaluated in CP mice, and the association between Hsp90 and biological functions of PSCs is further investigated in vitro. METHODS: The effects of Hsp90 inhibitor 17AAG on pancreatic fibrosis were assessed in caerulein-induced CP mice, and primary PSCs were used to determine the role of Hsp90 inhibitor 17AAG in vitro. RESULTS: We observed increased expression of Hsp90 in pancreatic tissues of caerulein-induced CP mice. Hsp90 inhibitor 17AAG ameliorated pancreatic inflammation and fibrosis in caerulein-induced CP mice. In vitro, Hsp90 inhibitor 17AAG inhibited TGFß1-induced activation and extracellular matrix accumulation of PSCs by blocking TGFßR-mediated Smad2/3 and PI3K /Akt/GSK-3ß signaling pathways.Hsp90 inhibitor 17AAG degraded TGFßRII by a ubiquitin-proteasome pathway, co-immunoprecipitation showed an interaction between Hsp90 and TGFßRII in PSCs. CONCLUSIONS: The study suggests that an Hsp90 inhibitor 17AAG remarkable prevents the development of pancreatic fibrosis in caerulein-induced CP mice, and suppresses activation and extracellular matrix accumulation of PSCs in vitro. The current results provide a potential treatment strategy based on Hsp90 inhibition for pancreatic fibrosis in CP.

The alterations of gut microbiota in mice with chronic pancreatitis.

BACKGROUND: The changes of intestinal microbiome are associated with inflammatory, metabolic, and malignant disorders, and there are no studies assessing the intestinal microbiota of mice with chronic pancreatitis (CP). Thus, we aim to investigate the variations in diversity, composition and function of intestinal microbiota in CP mice. METHODS: Sixteen male C57BL/6 mice were randomly selected, and divided into two groups, treated intraperitoneally with saline (normal control group, CT group) or ethanol + cerulein (experimental group, CP group) for 6 weeks. Body weight as measured in entire processes. Histopathological examination of CP index was conducted to verify the CP induction. Extracted DNA from colon samples was used for Illumina HiSeq sequencing of the bacterial V4 region of 16S rRNA gene and analyzed using Quantitative Insights Into Microbial Ecology (QIIME). Functional profiling of microbial communities was predicted with BugBase. RESULTS: Significant alterations of the gut microbiota were found in the CP mice compared to CT groups, as revealed by significant decrease in bacterial richness and diversity, declined the relative abundance of Lachnospiraceae_NK4A136, Ruminiclostridium and Roseburia, and increased the relative abundances of Bacteroides and Alloprevotella genera. Analysis of microbial community-level phenotypes revealed significant differences in nine phenotypes (aerobic, anaerobic, containing mobile elements, facultatively anaerobic, biofilm forming, gram-negative, gram-positive, potentially pathogenic, and stress tolerant) between CP group and CT group. CONCLUSIONS: This study indicated that mice with CP had a distinct microbiota profile.

Ets1-Mediated Acetylation of FoxO1 Is Critical for Gluconeogenesis Regulation during Feed-Fast Cycles.

The homeostatic balance of hepatic glucose uptake and production is exquisitely controlled by hormonal signals during feed-fast cycles. FoxO1, a transcription factor that functions in the regulation of glucose homeostasis, undergoes posttranslational modifications, such as acetylation, in response to hormonal signals, yet the mechanism remains poorly elucidated. Through expression profiling of 324 co-factors of CBP, a well-known acetyl-transferase of FoxO1, we identify Ets1 as a modulator of FoxO1 acetylation that is highly associated with feed-fast cycles. Mechanistic assays suggest that Ets1 enhances FoxO1 acetylation through the formation of a complex with CBP, which further promotes FoxO1 nuclear exclusion and inhibits its binding to gluconeogenic promoters. Functional studies further reveal that Ets1 inhibits gluconeogenesis under physiological and diabetes statuses, while the hyperinsulinemic-euglycemic clamp assay suggests hepatocyte Ets1 knockout mice have enhanced hepatic glucose production. Our study identifies Ets1 as an enhancer of FoxO1 acetylation and a repressor of hepatic gluconeogenesis in response to hormonal signals.