Ribosomal modification protein rimK-like family member A activates betaine-homocysteine S-methyltransferase 1 to ameliorate hepatic steatosis.

Nonalcoholic fatty liver disease (NAFLD) is a serious threat to public health, but its underlying mechanism remains poorly understood. In screening important genes using Gene Importance Calculator (GIC) we developed previously, ribosomal modification protein rimK-like family member A (RIMKLA) was predicted as one essential gene but its functions remained largely unknown. The current study determined the roles of RIMKLA in regulating glucose and lipid metabolism.

PANX1-mediated ATP release confers FAM3A's suppression effects on hepatic gluconeogenesis and lipogenesis.

Background: Extracellular adenosine triphosphate (ATP) is an important signal molecule. In previous studies, intensive research had revealed the crucial roles of family with sequence similarity 3 member A (FAM3A) in controlling hepatic glucolipid metabolism, islet β cell function, adipocyte differentiation, blood pressure, and other biological and pathophysiological processes. Although mitochondrial protein FAM3A plays crucial roles in the regulation of glucolipid metabolism via stimulating ATP release to activate P2 receptor pathways, its mechanism in promoting ATP release in hepatocytes remains unrevealed.

Serum uric acid levels and prognosis of patients with non-alcoholic fatty liver disease.

Uric acid (UA) is associated with non-alcoholic fatty liver disease (NAFLD). However, it is unclear whether UA plays a predictive role in NAFLD prognosis. This study aimed to explore the relationship between UA levels and mortality in NAFLD patients without severe renal disease.

Hepatocyte-secreted FAM3D ameliorates hepatic steatosis by activating FPR1-hnRNP U-GR-SCAD pathway to enhance lipid oxidation.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide; however, the underlying mechanisms remain poorly understood. FAM3D is a member of the FAM3 family; however, its role in hepatic glycolipid metabolism remains unknown. Serum FAM3D levels are positively correlated with fasting blood glucose levels in patients with diabetes.

FAM3A maintains metabolic homeostasis by interacting with F1-ATP synthase to regulate the activity and assembly of ATP synthase.

Reduced mitochondrial ATP synthase (ATPS) capacity plays crucial roles in the pathogenesis of metabolic disorders. However, there is currently no effective strategy for synchronously stimulating the expressions of ATPS key subunits to restore its assembly. This study determined the roles of mitochondrial protein FAM3A in regulating the activity and assembly of ATPS in hepatocytes.

Imipramine activates FAM3A-FOXA2-CPT2 pathway to ameliorate hepatic steatosis.

Mitochondrial FAM3A has been revealed to be a viable target for treating diabetes and nonalcoholic fatty liver disease (NAFLD). However, its distinct mechanism in ameliorating hepatic steatosis remained unrevealed. High-throughput RNA sequencing revealed that carnitine palmityl transferase 2 (CPT2), one of the key enzymes for lipid oxidation, is the downstream molecule of FAM3A signaling pathway in hepatocytes.

ATP Secretion and Metabolism in Regulating Pancreatic Beta Cell Functions and Hepatic Glycolipid Metabolism.

Diabetes (DM), especially type 2 diabetes (T2DM) has become one of the major diseases severely threatening public health worldwide. Islet beta cell dysfunctions and peripheral insulin resistance including liver and muscle metabolic disorder play decisive roles in the pathogenesis of T2DM. Particularly, increased hepatic gluconeogenesis due to insulin deficiency or resistance is the central event in the development of fasting hyperglycemia.

Targeting Cancer Metabolism Plasticity with JX06 Nanoparticles via Inhibiting PDK1 Combined with Metformin for Endometrial Cancer Patients with Diabetes.

Diabetes is closely related to the occurrence of endometrial cancer (EC) and its poor prognosis. However, there is no effective clinical treatment for EC patients with diabetes (patient ). To explore new therapeutic targets, Ishikawa is cultured with high glucose (Ishikawa ) mimicking hyperglycemia in patient .

Y/X-Chromosome-Bearing Sperm Shows Elevated Ratio in the Left but Not the Right Testes in Healthy Mice.

The sex chromosomes play central roles in determining the sex of almost all of the multicellular organisms. It is well known that meiosis in mammalian spermatogenesis produces ~50% Y- and ~50% X-chromosome-bearing sperm, a 1:1 ratio. Here we first reveal that the X-chromosome-encoded miRNAs show lower expression levels in the left testis than in the right testis in healthy mice using bioinformatics modeling of miRNA-sequencing data, suggesting that the Y:X ratio could be unbalanced between the left testis and the right testis.

Intracellular ATP Signaling Contributes to FAM3A-Induced PDX1 Upregulation in Pancreatic Beta Cells.

FAM3A is a recently identified mitochondrial protein that stimulates pancreatic-duodenal homeobox 1 (PDX1) and insulin expressions by promoting ATP release in islet β cells. In this study, the role of intracellular ATP in FAM3A-induced PDX1 expression in pancreatic β cells was further examined. Acute FAM3A inhibition using siRNA transfection in mouse pancreatic islets significantly reduced PDX1 expression, impaired insulin secretion, and caused glucose intolerance in normal mice.

FAM3A plays crucial roles in controlling PDX1 and insulin expressions in pancreatic beta cells.

So far, the mechanism that links mitochondrial dysfunction to PDX1 inhibition in the pathogenesis of pancreatic β cell dysfunction under diabetic condition remains largely unclear. This study determined the role of mitochondrial protein FAM3A in regulating PDX1 expression in pancreatic β cells using gain- and loss-of function methods in vitro and in vivo. Within pancreas, FAM3A is highly expressed in β, α, δ, and pp cells of islets.

Long Non-Coding RNA in the Pathogenesis of Cancers.

The incidence and mortality rate of cancer has been quickly increasing in the past decades. At present, cancer has become the leading cause of death worldwide. Most of the cancers cannot be effectively diagnosed at the early stage.

Mesenteric adipose tissue B lymphocytes promote local and hepatic inflammation in non-alcoholic fatty liver disease mice.

Mesenteric adipose tissue (MAT) inflammation is associated with non-alcoholic fatty liver disease (NAFLD), and immune cells play pivotal roles in the inflammation of adipose tissue. Here, we investigated the roles of MAT B lymphocytes in NAFLD. Mice fed with high-fat diet (HFD) and normal diet (ND) were killed in time gradients (4, 8 and 12 weeks).

Mesenteric lymph node CD4 T lymphocytes migrate to liver and contribute to non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is characterized by altered intestinal microbiota and intestinal immune disorder. Here we investigated the role of mesenteric lymph node (MLN) CD4 T lymphocytes in NAFLD. In high fat diet (HFD)-fed mice, the percentage ratios of Th1 to Th2 cells and Th17 to Treg cells were imbalanced in MLNs.

FAM3B (PANDER) functions as a co-activator of FOXO1 to promote gluconeogenesis in hepatocytes.

FAM3B, also known as PANcreatic DERived factor (PANDER), promotes gluconeogenesis and lipogenesis in hepatocytes. However, the underlying mechanism(s) still remains largely unclear. This study determined the mechanism of PANDER-induced FOXO1 activation in hepatocytes.

Mesenteric adipose tissue contributes to intestinal barrier integrity and protects against nonalcoholic fatty liver disease in mice.

Visceral adipose tissue (VAT) is related to nonalcoholic fatty liver disease (NAFLD). However, the role of mesenteric adipose tissue (MAT), part of the VAT, in NAFLD is unclear. In the present study, we monitored the liver and four depots of the VAT in high-fat diet (HFD)-feeding mice at multiple time points (4, 8, and 12 wk).

FAM3C activates HSF1 to suppress hepatic gluconeogenesis and attenuate hyperglycemia of type 1 diabetic mice.

FAM3C, a member of FAM3 gene family, has been shown to improve insulin resistance and hyperglycemia in obese mice. This study further determined whether FAM3C functions as a hepatokine to suppress hepatic gluconeogenesis of type 1 diabetic mice. In STZ-induced type 1 diabetic mouse liver, the FAM3C-HSF1-CaM signaling axis was repressed.

FAM3A enhances adipogenesis of 3T3-L1 preadipocytes via activation of ATP-P2 receptor-Akt signaling pathway.

FAM3A plays important roles in regulating hepatic glucose/lipid metabolism and the proliferation of VSMCs. This study determined the role and mechanism of FAM3A in the adipogenesis of 3T3-L1 preadipocytes. During the adipogenesis of 3T3-L1 preadipocytes, FAM3A expression was significantly increased.

Roles of microRNAs in immunopathogenesis of non-alcoholic fatty liver disease revealed by integrated analysis of microRNA and mRNA expression profiles.

Background: The integrative analysis of microRNA and mRNA expression profiles can elucidate microRNA-targeted gene function. We used this technique to elucidate insights into the immunological pathology of non-alcoholic fatty liver disease (NAFLD).

Methods: We analyzed differentially expressed microRNA and mRNA expression profiles of CD4+ T lymphocytes from the liver and mesenteric lymph nodes (MLNs) of mice with NAFLD using microarrays and RNA sequencing.

Study of Clinical and Genetic Risk Factors for Aspirin-induced Gastric Mucosal Injury.

Background: Current knowledge about clinical and genetic risk factors for aspirin-induced gastric mucosal injury is not sufficient to prevent these gastric mucosal lesions.

Methods: We recruited aspirin takers as the exposed group and healthy volunteers as the control group. The exposed group was categorized into two subgroups such as subgroup A as gastric mucosal injury diagnosed by gastroscopy, including erosion, ulcer or bleeding of the esophagus, stomach, or duodenum; subgroup B as no injury of the gastric mucosa was detected by gastroscopy.

Gut-derived lymphocyte recruitment to liver and induce liver injury in non-alcoholic fatty liver disease mouse model.

Background And Aim: Most studies focus on gut-derived factors like microbiota and its products and how they contribute to non-alcoholic fatty liver disease (NAFLD) progression. This study investigated whether the gut-derived lymphocytes could migrate to the liver and induce liver injury in NAFLD.

Methods: A high-fat diet induced an NAFLD mouse model, and lymphocytes were labeled with 1,1-dioctadecyl-3,3,3,3 tetramethylindotricarbocyanine iodide and carboxy-fluorescein succinimidyl ester, respectively, and intravenously injected to mice to monitor lymphocyte migration.

[Myosin light chain kinase involved in change of intestinal mucosal barrier function in nonalcoholic steatohepatitis mice model].

Objective: To investigate the role of myosin light chain kinase (MLCK) in intestinal barrier function in a mouse model with nonalcoholic steatohepatitis (NASH).

Methods: The C57BL/6 mice were randomly divided into five groups including control group, nonalcoholic fatty liver (NAFL) group, NAFL administrated with MLCK inhibitor ML-7 group, nonalcoholic steatohepatitis (NASH) group, NASH administrated with ML-7 group. Plasma ALT and AST were tested.