Regulation of plasma lipid homeostasis by hepatic lipoprotein lipase in adult mice.

LPL is a pivotal rate-limiting enzyme to catalyze the hydrolysis of TG in circulation, and plays a critical role in regulating lipid metabolism. However, little attention has been paid to LPL in the adult liver due to its relatively low expression. Here we show that endogenous hepatic LPL plays an important physiological role in plasma lipid homeostasis in adult mice. We generated a mouse model with the Lpl gene specifically ablated in hepatocytes with the Cre/LoxP approach, and found that specific deletion of hepatic Lpl resulted in a significant decrease in plasma LPL contents and activity. As a result, the postprandial TG clearance was markedly impaired, and plasma TG and cholesterol levels were significantly elevated. However, deficiency of hepatic Lpl did not change the liver TG and cholesterol contents or glucose homeostasis. Taken together, our study reveals that hepatic LPL is involved in the regulation of plasma LPL activity and lipid homeostasis.

Reflections on the complex mechanisms of endometriosis from the perspective of ferroptosis.

Ferroptosis is a novel type of iron-dependent programmed cell death characterised by intracellular iron overload, increased lipid peroxidation and abnormal accumulation of reactive oxygen species.It has been implicated in the progression of several diseases including cancer, ischaemia-reperfusion injury, neurodegenerative diseases and liver disease. The etiology of endometriosis (EMS) is still unclear and is associated with multiple factors, often accompanied by various forms of cell death and a complex microenvironment. In recent decades, the role of non-traditional forms of cell death, represented by ferroptosis, in endometriosis has come to the attention of researchers. This article reviews the transitional role of iron homeostasis in the development of ferroptosis, the characteristics and regulatory mechanisms of ferroptosis, and focuses on summarising the links between iron death and various pathogenic mechanisms of EMS, including oxidative stress, dysregulation of lipid metabolism, inflammation, autophagy and epithelial-mesenchymal transition. The possible applications of ferroptosis in the treatment of EMS, future research directions and current issues are discussed with the aim of providing new ideas for further understanding of EMS.

Potential clinical implications of iron metabolism in ovarian endometriosis.

OBJECTIVE: The purpose of this study was to investigate iron metabolism indices in ovarian endometriosis (OEMs) and to demonstrate the potential clinical implications in the initiation and development of OEMs. METHODS: Three datasets in Gene Expression Omnibus (GEO) database were selected to assess the expression levels of iron metabolites in endometrial tissues from patients with EMs and the health. To evaluate the differential expression of serum iron indices , hospitalized patients with OEMs and health examinees in Jilin University Second Hospital from November 2018 to December 2019 were recruited. Serum samples were obtained from 38 patients with OEMs and 36 health examinees. To compare the iron metabolism between peripheral circulation blood and local ectopic lesion, cyst fluid samples were obtained from 15 patients with ovarian chocolate cyst at the time of surgery. Iron metabolism indices include iron, transferrin (TF), ferritin, and unsaturated iron-binding capacity (UIBC)), which were measured by automatic biochemical analyzer. RESULTS: The present study indicated the increased levels of the iron storage protein, ferritin, in the endometriotic tissues of patients with EMs. The expression of iron and ferritin in cyst fluid of patients with OEMs showed higher than that in serum, the results of TF and UIBC were opposite (P < 0.05). There was no statistical difference in the content of iron metabolites between patients with OEMs and the healthy examinees(P > 0.05). CONCLUSION: The ovarian chocolate cyst fluid and endometriotic tissues in patients with OEMs could more directly reflect the pathological changes of local ectopic lesion, which usually manifested as high levels of free iron and/or iron deposits in the ectopic sites. The implications of our work suggest iron metabolites in the serum may have potentially limited value as circulating biomarkers for OEMs. The iron variation in local lesions may be not only regulated by liver that mainly manipulate the systematic iron homeostasis, but also be tuned by the iron regulatory protein (IRP)/ iron responsive element (IRE) system. In summary, the iron metabolites, especially the iron and ferritin in the cyst fluid and endometriotic tissues, are meaningful biomarkers involved in the process of pathophysiology and pathogenesis of OEMs.

Pseudohyperchloremia caused by the long-term use of phenobarbital and sodium bromide compound tablets: a case report.

Background: Serum chloride (Cl-), which is an important analyte that reflects the electrolyte and acid-base balance in humans, is affected by several specific agents or substances. It has been reported that the abuse of bromine-containing drugs, such as bromvalerylurea may lead to pseudohyperchloremia, which is very rare yet, caused by the treatment dose of bromine-containing drugs. In this case report, we describe an epilepsy patient whose serum Cl- was falsely elevated due to the long-term use of phenobarbital and sodium bromide compound tablets. We also discuss the anti-interference capacity of different analyzers and the disturbance of bromide-containing drugs in Cl- determination. Case Description: A 34-year-old woman diagnosed with epilepsy for 11 years was admitted to our hospital for further treatment. She had increasingly frequent loss of consciousness and seizures. Her medication history included carbamazepine, levetiracetam, phenobarbital and sodium bromide compound tablets. The video electroencephalogram (VEEG) was moderately abnormal. No obvious abnormality was found in blood routine test, liver and kidney function, except an aberrantly elevated serum Cl- level of 130 mmol/L; however, the patient did not present with the relevant signs and symptoms of hyperchloremia, such as thirst, fatigue, nausea and vomiting. Subsequently, we used three different analyzers to determine her Cl- level and obtained the following results: an arterial blood Cl- level of 107 mmol/L; a serum Cl- level of 112 mmol/L; and no result. Reviewing her medical history, we discovered that the patient had been taking phenobarbital and sodium bromide compound tablets for 6 months to treat her seizures. Her serum bromide was 4.89 mmol/L, which may cause pseudohyperchloremia. After changing her treatment to phenobarbital tablets, her serum Cl- returned to the normal range (106 mmol/L). Conclusions: Bromide-containing drugs can cause a falsely elevated Cl- level. When pseudohyperchloremia is suspected, different methods or instruments should be used to measure Cl- levels.

The role of BMP15 and GDF9 in the pathogenesis of primary ovarian insufficiency.

Endocrine and paracrine signals can be key regulators of ovarian physiology. The oocyte secretes growth factors which directly induce follicular development by a complex paracrine signalling process, and the transforming growth factorß (TGF-ß) superfamily has a pivotal role in this process. The bone morphogenetic protein 15 (BMP15) and growth differentiation factor 9 (GDF9) genes are relevant members of the TGF-ß superfamily that encode proteins secreted by the oocytes into the ovarian follicles, where they contribute to creating an environment supporting follicle selection and growth. Their main functions include regulating cellular proliferation/differentiation, follicular survival/atresia, and oocyte maturation. Recent functional studies have validated genetic factors (Progesterone receptor membrane component 1 (PGRMC1)), Fragile X mental retardation 1 (FMR1, GDF9 and BMP15) as being causative of primary ovarian insufficiency (POI), BMP15/GDF9 gene variants were found to have a high incidence on the POI phenotype. This review considers the most recent research regarding the role of BMP15 and GDF9 in the genetic control of follicular development, paying special attention to the pathogenesis of POI.