Результаты поиска

Investigation of adult-onset multiple acyl-CoA dehydrogenase deficiency associated with peripheral neuropathy.

Multiple Acyl-CoA dehydrogenase deficiency (MADD), one of the most common lipid storage myopathies (LSMs), is a heterogeneous inherited muscular disorder that is pathologically characterized by numerous lipid droplets in muscle fibers due to lipid metabolism disturbance. MADD exhibits a wide range of clinical features, including skeletal muscle weakness and multisystem dysfunctions. However, MADD, as well as other types of LSM, associated with peripheral neuropathy has rarely been reported during the past four decades. Here, we present four Chinese patients affected by MADD with peripheral neu…

Effect of L-carnitine on the zidovudine-induced destruction of human myotubes. Part I: L-carnitine prevents the myotoxicity of AZT in vitro.

BACKGROUND: Zidovudine (AZT) as used in the treatment of AIDS, causes a mitochondrial myopathy characterized by depletion of mitochondrial DNA, enzymatic defects in the respiratory chain system, and accumulation of lipid droplets. Most of these changes are also seen in normal human myotubes treated with AZT. Because L-carnitine plays a major role in the transport of long chain fatty acids across the inner mitochondrial membrane and facilitates the beta-oxidation of fatty acids, we examined the effect of L-carnitine in preventing the destructive effect of AZT on the mitochondria and the myotube…

Olanzapine causes non-alcoholic fatty liver disease via inhibiting the secretion of apolipoprotein A5.

OBJECTIVES: Long-term treatment of olanzapine, the most widely-prescribed second-generation antipsychotic, remarkably increases the risk of … sfected with siRNA and scrambled siRNA (negative control), respectively. We observed the changes in lipid droplets within liver tissues and cells using oil red O staining and fat deposition in liver tissues using HE staining. The mRNA and protein levels of ApoA5 were determined by real-time PCR and Western blotting, respectively. RESULTS: After intervention wit …

CCN5 Drives Leydig Cell Aging and Testicular Dysfunction: Insights into Fibrosis, Lipid Dysregulation, and Therapeutic Potential.

Leydig cells' (LCs') senescence is an important reason for the decline of testicular function in elderly men. Cellular communication network factor 5 (CCN5) regulates lipid metabolism and cellular fibrosis through multiple mechanisms. However, its role in LCs' aging and the underlying molecular mechanisms remain unclear. This study aimed to elucidate the effects and molecular mechanisms by which CCN5 drives aging phenotypes in LCs and to evaluate the potential of targeting CCN5 as a therapeutic strategy for testicular aging. CCN5 expression was located in LCs and elevated in aged testis. Overe

Adipocyte-specific disruption of fat-specific protein 27 causes hepatosteatosis and insulin resistance in high-fat diet-fed mice.

White adipose tissue (WAT) functions as an energy reservoir where excess circulating fatty acids are transported to WAT, converted to triglycerides, and stored as unilocular lipid droplets. Fat-specific protein 27 (FSP27, CIDEC in humans) is a lipid-coating protein highly expressed in mature white adipocytes that contributes to unilocular lipid droplet formation. However, the influence of FSP27 in adipose tissue on whole-body energy homeostasis remains unclear. Mice with adipocyte-specific disruption of the Fsp27 gene (Fsp27(ΔAd)) were generated using an aP2-Cre transgene with the Cre/LoxP sys…

Cooperation of acylglycerol hydrolases in neuronal lipolysis.

Genetic and biochemical evidence has established DDHD-domain containing 2 (DDHD2) as the principal triacylglycerol (TAG) hydrolase in neuronal lipolysis of cytosolic lipid droplets. In this issue of Journal of Lipid Research, Hofer et al. report that DDHD2 cooperates with adipose triglyceride lipase, the principal TAG hydrolase in adipose lipolysis, contributing to cytosolic hydrolysis of both TAG and diacylglycerols in murine neuroblastoma cells and primary cortical neurons via different configurations of the lipases. This finding highlights the complexity of cytosolic acylglycerol hydrolysis…

SETD6-mediated methylation of PPARγ establishes a transcriptional feedback circuit promoting lipid accumulation in liver-derived cells.

Peroxisome proliferator-activated receptor gamma (PPARγ) is a key transcriptional regulator of genes mediating adipogenesis (fat-cell differentiation), and lipid storage in several cell types like hepatocytes. As such, its regulation is crucial for cell and organismal physiology. Indeed, PPARγ's activity is regulated by multiple mechanisms, including post-transcriptional modifications, which, when dys-coordinated, may contribute to the pathogenesis of various states, including obesity, insulin resistance, and fatty liver disease. Here, we demonstrate that SETD6 binds to and methylates PPARγ at

Platelet-derived mitochondria regulate lipid metabolism in nonalcoholic steatohepatitis through extracellular vesicles.

BACKGROUND AND AIMS: Immune system activation, along with lipotoxicity due to excessive lipid droplet (LD) accumulation in the liver, are key drivers of NASH. Extracellular vesicles (EVs) released by cells that carry biological signals contribute to intercellular communication. However, the roles of immune cell-derived EVs in the pathogenesis of NASH are unclear. APPROACH AND RESULTS: Platelets are abundant in blood. We explored the role of platelet-derived EVs (pEVs) in LD accumulation from 30 patients with nonalcoholic fatty liver disease of different severity as well as 20 healthy subjects

Type of hormonal treatment administered to induce vitellogenesis in European eel influences biochemical composition of eggs and yolk-sac larvae.

Egg biochemical composition is among the main factors affecting offspring quality and survival during the yolk-sac stage, when larvae depend exclusively on yolk nutrients. These nutrients are primarily embedded in the developing oocytes during vitellogenesis. In aquaculture, assisted reproduction procedures may be applied enabling gamete production. For the European eel (Anguilla anguilla), reproductive treatment involves administration of pituitary extracts from carp (CPE) or salmon (SPE) to induce and sustain vitellogenesis. In the present study, we compared the influence of CPE and SPE trea

Nuclear receptor Rev-erb-α mediates palmitic acid-induced lipid peroxidation in cardiomyocytes.

Abnormal cardiac lipid metabolism is a major contributor to cardiovascular disease (CVD). The nuclear receptor Rev-erb-α is recognized as a regulator of lipid metabolism; however, its role in cardiomyocyte lipotoxicity remains undefined. This study aims to investigate the functional role of Rev-erb-α in palmitic acid (PA)-induced lipid accumulation and peroxidation in cardiomyocytes. H9c2 cardiomyocytes are treated with the canonical Rev-erb agonists SR9009 and GSK4112 in combination with PA. Intracellular lipid droplet accumulation is quantified using Oil Red O, Nile red, and BODIPY 493/503 s

Recent Advances in Triacylglycerol Mobilization by the Gut.

Dietary lipid absorption and lipoprotein secretion by the gut are important in maintaining whole-body energy homeostasis and have significant implications for health and disease. The processing of dietary lipids, including storage within and subsequent mobilization and transport from enterocyte cytoplasmic lipid droplets or other intestinal lipid storage pools (including the secretary pathway, lamina propria and lymphatics) and secretion of chylomicrons, involves coordinated steps that are subject to various controls. This review summarizes recent advances in our understanding of the mechanism…

Arachidonic acid suppresses lung cancer cell growth and modulates lipid metabolism and the ERK/PPARγ signaling pathway.

Lung cancer remains the leading cause of cancer-related mortality worldwide, necessitating the development of new treatment strategies. Arachidonic acid (ARA), a polyunsaturated fatty acid, shows promise in cancer therapy due to its potential anti-tumor effects, although its role in lung cancer remains unclear. This study investigated the effects and underlying mechanism of ARA on A549 and NCI-H1299 lung cancer cells. In vitro assays were used to assess cell viability, apoptosis, colony formation, lipid droplet formation, and changes in cellular lipid content. ARA dose-dependently suppressed c

Совпадение в полном тексте источника
… To further investigate the contribution of lipid droplet formation to lung cancer cell malignancy, GW9662, a well-characterized PPARγ antagonist that inhibits lipid droplet formation [ 38 , 39 ], was used to treat A549 and NCI-H1299 cells. … The paradoxical role of ARA as both an essential fatty acid and an inhibitor of lipid droplet might be because the formation lipid droplets are primarily formed through the accumulation of saturated and monounsaturated fatty acids. …

Intestinal lipid absorption and lipoprotein formation.

PURPOSE OF REVIEW: To summarize the evidence for the presence of two lipid absorption pathways and their regulation. RECENT FINDINGS: Lipid absorption involves hydrolysis of dietary fat in the lumen of the intestine, followed by the uptake of hydrolyzed products by enterocytes. Lipids are resynthesized in the endoplasmic reticulum and are either secreted with chylomicrons and HDLs or stored as cytoplasmic lipid droplets. Lipids in the droplets are hydrolyzed and are secreted at a later time. Secretion of lipids by the chylomicron and HDL pathways are dependent on microsomal triglyceride trans…

Lipid remodeling enables adaptation to chronic hyperosmotic stress.

Lipid droplets (LDs) accumulate in response to diverse cellular stresses. However, their regulation and physiological roles remain poorly understood in most contexts. Here, we show that in budding yeast, chronic hyperosmotic stress induces sustained LD accumulation. Unlike the transient LD response observed during acute osmotic shock, chronic stress triggers prolonged, Dga1-dependent triacylglycerol synthesis. In the absence of triacylglycerol synthesis, cellular fitness is impaired. Lipidomic profiling reveals extensive membrane remodeling during chronic hyperosmotic stress, most notably an i…

The Interplay Between Cellular Senescence and Lipid Metabolism in the Progression of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD).

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease (NAFLD), is now recognized as the leading cause of chronic liver disease worldwide. MASLD spans a spectrum ranging from simple steatosis to metabolic dysfunction-associated steatohepatitis (MASH) and is linked to progressive fibrosis and ultimately hepatocellular carcinoma (HCC). Growing evidence implicates cellular senescence (CS) and lipid droplets (LDs) as key drivers of disease progression, although their interaction remains poorly characterized. This review provides an i…

Role of Phospholipid Flux during Milk Secretion in the Mammary Gland.

Lipids are a complex group of chemical compounds that are a significant component of the human diet and are one of the main constituents of milk. In mammals, lipids are produced in the milk-secreting cells in the form of milk fat globules. The chemical properties of these compounds necessitate developing separate processes for effective management of non-polar substances in the polar environment of the cell, not only during their biosynthesis and accumulation in the cell interior and secretion of intracytoplasmic lipid droplets outside the cell, but also during digestion in the offspring. Phos…

Maternal tocotrienol supplementation protects early embryo mitochondria from allergic asthma stress.

BACKGROUND: To determine whether maternal tocotrienol-rich fraction supplementation restores mitochondrial-volume, -fusion, and -interaction with lipid droplets in 2-cell embryos of ovalbumin-induced allergic asthma mice. METHOD: Female BALB/c mice were sensitised and challenged with ovalbumin to induce allergic asthma and subsequently supplemented with tocotrienol-rich fraction. Two-cell embryos were collected for ultrastructural evaluation using transmission electron microscopy (TEM) and for gene expression analysis using Fluidigm qPCR including developmental potential thru microscopic anal…

ApoE lipidation state directs immunometabolic reprogramming of human microglia.

INTRODUCTION: ApoE ε4 is the strongest genetic risk factor for Alzheimer's disease (AD). Emerging evidence suggests that ApoE4 increases AD risk by disrupting microglial metabolism and function. However, whether ApoE lipidation state contributes to microglial dysfunction remains poorly understood. METHODS: Human microglia were treated with lipid-free (LF) or lipid-bound ApoE3 or ApoE4. Label-free, live-cell holotomography and global proteomics were used to assess isoform- and lipidation-specific effects on lipid droplet (LD) dynamics, mitochondrial morphology, and microglial phenotype. RESUL

Understanding the early onset of intracellular lipid accumulation induced by oleic and palmitic acids in HepG2 cells.

Increasing hepatic lipid accumulation is the primary cause of non-alcoholic fatty liver disease (NAFLD), which has become an emerging health concern globally. Many studies have used the HepG2 cell-based in vitro model of NAFLD to investigate intracellular lipid accumulation after several hours of exposure to free fatty acids (FFAs). However, the molecular mechanisms underlying the early onset of lipid accumulation are yet to be unveiled. In this study, we examined oleic acid (OA) and palmitic acid (PA)- induced lipid accumulation in HepG2 cells at early time points, i.e., in minutes. Using Oil

PPARγ mediated enhanced lipid biogenesis fuels Mycobacterium tuberculosis growth in a drug-tolerant hepatocyte environment.

Mycobacterium tuberculosis (Mtb) infection of the lungs, besides producing prolonged cough with mucus, also causes progressive fatigue and cachexia with debilitating loss of muscle mass. While anti-tuberculosis (TB) drug therapy is directed toward eliminating bacilli, the treatment regimen ignores the systemic pathogenic derailments that probably dictate TB-associated mortality and morbidity. Presently, it is not understood whether Mtb spreads to metabolic organs and brings about these impairments. Here, we show that Mtb creates a replication-conducive milieu of lipid droplets in hepatocytes b…