Hepatocyte-Specific HuR Protects Against Acetaminophen-Induced Liver Injury in Mice.

Acetaminophen (APAP) overdose is a major cause of drug-induced liver injury (DILI) in many countries. Hepatocyte proliferation, autophagy and antioxidant capacity are crucial to the prognosis of APAP-induced liver injury, but the underlying mechanisms are not fully understood. Here, we found that human antigen R (HuR) protein expression was markedly increased in the model of APAP-induced liver injury, and conditional hepatocyte-specific HuR knockout aggravated APAP-induced liver injury in mice.

NR4A1 counteracts JNK activation incurred by ER stress or ROS in pancreatic β-cells for protection.

Sustained hyperglycaemia and hyperlipidaemia incur endoplasmic reticulum stress (ER stress) and reactive oxygen species (ROS) overproduction in pancreatic β-cells. ER stress or ROS causes c-Jun N-terminal kinase (JNK) activation, and the activated JNK triggers apoptosis in different cells. Nuclear receptor subfamily 4 group A member 1 (NR4A1) is an inducible multi-stress response factor.

NR4A1 retards adipocyte differentiation or maturation via enhancing GATA2 and p53 expression.

Nuclear receptor subfamily 4 group A member 1 (NR4A1) is an orphan nuclear receptor with diverse functions. It has been reported that NR4A1, as a transcriptional activator, is implicated in glucose and lipid metabolism. The aim of this study was to investigate the regulatory role of NR4A1 in adipogenesis and explore the underlying mechanisms.

Hydrogen sulfide improves diabetic wound healing in ob/ob mice via attenuating inflammation.

Background: The proposed mechanisms of impaired wound healing in diabetes involve sustained inflammation, excess oxidative stress and compromised agiogenesis. Hydrogen sulfide (HS) has been reported to have multiple biological activities. We aim to investigate the role of HS in impaired wound healing in ob/ob mice and explore the possible mechanisms involved.

GLP-1/GLP-1R Signaling in Regulation of Adipocyte Differentiation and Lipogenesis.

Background/aims: The aim of this study was to determine the direct role of liraglutide (LG) in adipogenesis and lipid metabolism.

Methods: Lipid accumulation was evaluated by oil red O staining, quantitative real-time PCR (qPCR) was performed to determine glucagon-like peptide 1 receptor (GLP-1R), fatty acid synthase (FASN) and adipose triglyceride lipase (ATGL) expression in 3T3-L1 preadipocytes, differentiated adipocytes and in adipose tissues from mice. The effects of LG on 3T3-L1 adipogenesis and lipid metabolism were analyzed with qPCR, Western Blotting, oil red O staining, immunohistochemistry (IHC) and immunofluorescence (IF).

The stress-response molecule NR4A1 resists ROS-induced pancreatic β-cells apoptosis via WT1.

Pancreatic β-cells often face endoplasmic reticulum stress and/or ROS-associated oxidative stress under adverse conditions. Our previous work has verified that NR4A1 protects pancreatic β-cells from ER-stress induced apoptosis. However, It remains unknown whether NR4A1 is able to protect pancreatic β-cells against ROS-associated oxidative stress.

Cytochrome P450 (CYP) epoxygenases as potential targets in the management of impaired diabetic wound healing.

Epoxyeicosatrienoic acids (EETs) are the epoxidation products of arachidonic acid catalyzed by cytochrome P450 (CYP) epoxygenases, which possess multiple biological activities. In the present study, we aimed to explore the role and effects of CYP epoxygenases/EETs in wound healing in ob/ob mice. Full-thickness skin dorsal wounds were made on ob/ob mice and C57BL/6 control mice.

The Effect of Growth Hormone on Lipid Accumulation or Maturation in Adipocytes.

Background: Adipogenesis of adipocytes includes two stages: initiation and maturation. Growth hormone (GH) secretion is decreased in obese subjects and GH levels are inversely correlated with abdominal fat mass. The effects of growth hormone (GH) on lipids accumulation or maturation of adipocytes remains elusive.

Signal transducer and activator of transcription 5B (STAT5B) modulates adipocyte differentiation via MOF.

The role and mechanism of signal transducer and activator of transcription 5B (STAT5B) in adipogenesis remain unclear. In this study, our data showed that Males absent on the first (MOF) protein expression was increased during 3 T3-L1 preadipocytes differentiation accompanied with STAT5B expression increasing. Over-expression STAT5B enhanced MOF promoter trans-activation in HeLa cells.

Effects of hydrogen sulfide on high glucose-induced glomerular podocyte injury in mice.

The aim of this study was to assess the effects of hydrogen sulfide on high glucose-induced mouse podocyte (MPC) injury and the underlying mechanisms. Mouse podocytes were randomly divided into 4 groups, including high glucose (HG), normal glucose (NG), normal glucose + DL-propargylglycine (PPG), and high glucose + NaHS (HG + NaHS) groups for treatment. Then, ZO-2, nephrin, β-catenin, and cystathionine γ-lyase (CSE) protein expression levels were determined by western blot.

The Orphan Nuclear Receptor NR4A1 Protects Pancreatic β-Cells from Endoplasmic Reticulum (ER) Stress-mediated Apoptosis.

The role of NR4A1 in apoptosis is controversial. Pancreatic β-cells often face endoplasmic reticulum (ER) stress under adverse conditions such as high free fatty acid (FFA) concentrations and sustained hyperglycemia. Severe ER stress results in β-cell apoptosis.

TSH/TSHR Signaling Suppresses Fatty Acid Synthase (FASN) Expression in Adipocytes.

TSH/TSHR signaling plays a role in the regulation of lipid metabolism in adipocytes. However, the precise mechanisms are not known. In the present study, we determined the effect of TSH on fatty acid synthase (FASN) expression, and explored the underlying mechanisms.

Involvement of CSE/ H2S in high glucose induced aberrant secretion of adipokines in 3T3-L1 adipocytes.

Background: Deregulated secretion of adipokines contributes to subclinical systemic inflammation associated with type 2 diabetes mellitus (T2DM). However, the mechanisms underlying are not fully understood. Hydrogen sulfide (H2S), as an endogenous gasotransmitter, possesses an anti-inflammation activity.

Hydrogen sulfide suppresses high glucose-induced expression of intercellular adhesion molecule-1 in endothelial cells.

Hydrogen sulfide (H₂S) is a newly identified endogenous gasotransmitter that has been implicated in the pathophysiology of several biologic systems. However, the role of H₂S in the pathogenesis of diabetic vascular injury remains unclear. The aims of this study were to determine the effect of H₂S on the high glucose (HG)-induced expression of intercellular adhesion molecule-1 (ICAM-1) in human umbilical vein endothelial cells and to explore the possible underlying mechanisms.