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Biogenesis of LDs in general glial cells. During oxidative stress, glial cells take in glucose from the blood and turn glucose into lactate. Lactate is subsequently transported to neurons and converted into FAs. The process of LD de novo synthesis is divided into three main steps: (i) nucleation, (ii) growth, and (iii) budding. Firstly, an oil lens structure forms between two lipid monolayers of the ER, limiting membrane by ER resident proteins such as BSCL2/seipin, which is the key step of nucleation. Afterwards, small-volume LDs diffuse and fuse with the large ones. Finally, LDs sprout out of the ER membrane.
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Lipid droplets (LDs) are the organelles for storing neutral lipids, which are broken down when energy is insufficient. It has been suggested that excessive accumulation of LDs can affect cellular function, which is important to coordinate homeostasis of lipids in vivo. Lysosomes play an important role in the degradation of lipids, and the process o...
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... Nevertheless, APOEε4 (a specific genetic variant) disrupts FA metabolism coupled between neurons and astrocytes [26]. For PD patients, LDs appear to relocate between the neurons and glial cells [29]. This pattern indicates the significance of maintaining lipid homeostasis. The structure of LDs and biological processes in the CNS are presented in Fig. ...
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... [60,61]. Besides, genetic studies have revealed that some patients with DLB have mutations in the αsynuclein gene (SNCA), which acts as a lipid-binding protein that interacts with phospholipids and fatty acids to participate in the process of lipophagy, impairing a variety of subcellular functions and leading to dysregulation of lipid metabolism, which in turn may contribute to the development of MI [62]. Most importantly, there is growing evidence of an inflammatory response in the blood of DLB patients, such as elevated expression of chronic inflammatory factors such as Tumor Necrosis Factor-α (TNF-α), Interleukin-1β (IL-1β), and Interleukin-6 (IL-6) compared to controls [63]. ...
Several studies have demonstrated a correlation between neurodegenerative diseases (NDDs) and myocardial infarction (MI), yet the precise causal relationship between these remains elusive. This study aimed to investigate the potential causal associations of genetically predicted Alzheimer's disease (AD), dementia with Lewy bodies (DLB), Parkinson's disease (PD), and multiple sclerosis (MS) with MI using two-sample Mendelian randomization (TSMR). Various methods, including inverse variance weighted (IVW), weighted median (WM), MR-Egger regression, weighted mode, and simple mode, were employed to estimate the effects of genetically predicted NDDs on MI. To validate the analysis, we assessed pleiotropic effects, heterogeneity, and conducted leave-one-out sensitivity analysis. We identified that genetic predisposition to NDDs was suggestively associated with higher odds of MI (OR_IVW=1.07, OR_MR-Egger=1.08, OR_WM=1.07, OR_weighted mode=1.07, OR_simple mode=1.10, all P<0.05). Furthermore, we observed significant associations of genetically predicted DLB with MI (OR_IVW=1.07, OR_MR-Egger=1.11, OR_WM=1.09, OR_weighted mode=1.09, all P<0.05). However, there was no significant causal evidence of genetically predicted PD and MS in MI. Across all MR analyses, no horizontal pleiotropy or statistical heterogeneity was observed (all P>0.05). Additionally, results from MRPRESSO and leave-one-out sensitivity analysis confirmed the robustness of the causal effect estimations for genetically predicted AD, DLB, PD, and MS on MI. This study provides further support for the causal effects of AD on MI and, for the first time, establishes robust causal evidence for the detrimental effect of DLB on the risk of MI. Our findings emphasize the importance of monitoring the cardiovascular function of the elderly experiencing neurodegenerative changes.
... LDL-C is formed by the combination of lowdensity lipoprotein and cholesterol (Lan et al. 2023). There is evidence that inhibited lipophagy leads to LD accumulation, whereas activated lipophagy Previous studies have shown that lipophagy alleviates Cd-caused LDs accumulation in placental and hepatocytes Zhang et al. 2023). ...
Neural tube defects (NTDs) represent a prevalent and severe category of congenital anomalies in humans. Cadmium (Cd) is an environmental teratogen known to cause fetal NTDs. However, its underlying mechanisms remain elusive. This study aims to investigate the therapeutic potential of lipophagy in the treatment of NTDs, providing valuable insights for future strategies targeting lipophagy activation as a means to mitigate NTDs.We successfully modeled NTDs by Cd exposure during pregnancy. RNA sequencing was employed to investigate the transcriptomic alterations and functional enrichment of differentially expressed genes in NTD placental tissues. Subsequently, pharmacological/genetic (Atg5-/- placentas) experiments confirmed that inducing placental lipophagy can alleviate Cd induced-NTDs. We found that Cd exposure caused NTDs. Further analyzed transcriptomic data from the placentas with NTDs which revealed significant downregulation of low-density lipoprotein receptor associated protein 1(Lrp1) gene expression responsible for positive regulation of low-density lipoprotein cholesterol (LDL-C) transport. Correspondingly, there was an increase in maternal serum/placenta/amniotic fluid LDL-C content. Subsequently, we have discovered that Cd exposure activated placental lipophagy. Pharmacological/genetic (Atg5-/- placentas) experiments confirmed that inducing placental lipophagy can alleviate Cd induced-NTDs. Furthermore, our findings demonstrate that activation of placental lipophagy effectively counteracts the Cd-induced elevation in LDL-C levels. Lipophagy serves to mitigate Cd-induced NTDs by reducing LDL-C levels within mouse placentas.
Diabetic kidney disease (DKD), a significant complication associated with diabetes mellitus, presents limited treatment options. The progression of DKD is marked by substantial lipid disturbances, including alterations in triglycerides, cholesterol, sphingolipids, phospholipids, lipid droplets, and bile acids (BAs). Altered lipid metabolism serves as a crucial pathogenic mechanism in DKD, potentially intertwined with cellular ferroptosis, lipophagy, lipid metabolism reprogramming, and immune modulation of gut microbiota (thus impacting the liver-kidney axis). The elucidation of these mechanisms opens new potential therapeutic pathways for DKD management. This research explores the link between lipid metabolism disruptions and DKD onset.
The impacts of dimethylation of 4‐Amino‐1,8‐Naphthalimide (ANI) on its photophysical properties are reported. The resulting 4‐DiMe‐ANI displays completely different fluorescence properties, conferring it ability to selectively label lipid droplets in living cells. A comprehensive photophysical study revealed that this selectivity arises from an Internal Charge Transfer favored in lipophilic media to the detriment of a non‐emissive TICT in more polar media. This results in a very high “LDs/Cytosol” signal ratio, enabling LDs to be imaged with an excellent signal‐to‐noise ratio, and positioning its performance above that of the BODIPY 493/503 commonly used to image LDs.
Hexagonal boron nitride (hBN) is an emerging 2D material attracting significant attention due to its superior electrical, chemical, and therapeutic properties. However, inhalation toxicity mechanisms of hBN in human lung cells are poorly understood. Here, cellular interaction and effects of hBN nanosheets is investigated in alveolar epithelial cells cultured on porous inserts and exposed under air-liquid interface conditions for 24 h. hBN is taken up by the cells as determined in a label-free manner via RAMAN-confocal microscopy, ICP-MS, TEM, and SEM-EDX. No significant (p > 0.05) effects are observed on cell membrane integrity (LDH release), epithelial barrier integrity (TEER), interleukin-8 cytokine production or reactive oxygen production at tested dose ranges (1, 5, and 10 µg cm-2 ). However, it is observed that an enhanced accumulation of lipid granules in cells indicating the effect of hBN on lipid metabolism. In addition, it is observed that a significant (p < 0.05) and dose-dependent (5 and 10 µg cm-2 ) induction of autophagy in cells after exposure to hBN, potentially associated with the downstream processing and breakdown of excess lipid granules to maintain lipid homeostasis. Indeed, lysosomal co-localization of lipid granules supporting this argument is observed. Overall, the results suggest that the continuous presence of excess intracellular lipids may provoke adverse outcomes in the lungs.
