Perilipin Research Articles

JMJD8 regulates adipocyte hypertrophy through the interaction with Perilipin 2.

Adipocyte hypertrophy significantly contributes to insulin resistance and metabolic dysfunction. Our previous research established JMJD8 as a mediator of insulin resistance, noting its role in promoting adipocyte hypertrophy within an autonomous adipocyte context. Nevertheless, the precise mechanisms underlying this phenomenon remained elusive. In this study, we employed a proteomics approach to identify Perilipin 2 (PLIN2), a lipid-associated protein, as a binding partner of JMJD8. Our investigations unveiled a robust interaction between JMJD8 and PLIN2, demonstrating its pivotal role in driving adipocyte hypertrophy and promoting insulin resistance. Furthermore, we show that JMJD8 suppresses fasting-induced lipophagy and curtails energy production, which involves inhibition of PLIN2 phosphorylation. These findings underscore the critical roles played by JMJD8 and PLIN2 in governing lipid droplet homeostasis, while also shedding light on a potential regulatory mechanism governing fat store mobilization during energy deprivation.

The Expression of Thymic AQP7 and Perilipin 1 (PLIN1) in Rats Fed a High-Fructose Diet is Modified by Voluntary Physical Activity

The Expression of Thymic AQP7 and Perilipin 1 (PLIN1) in Rats Fed a High-Fructose Diet is Modified by Voluntary Physical Activity

Sesamol Ameliorates Lipid Deposition by Maintaining the Integrity of the Lipid Droplet-Mitochondria Connection in Diabetic Nephropathy.

Diabetic nephropathy (DN) is a serious complication of diabetes mellitus and an important cause of end-stage renal disease (ESRD). However, there is still a lack of effective prevention and treatment strategies in clinical practice. As a metabolic disease, DN is accompanied by renal ectopic lipid deposition, and the deposited lipids further aggravate kidney injury. However, the molecular mechanism of renal ectopic lipid deposition is currently unknown. In this study, we observed changes in lipid droplet (LD)-mitochondria connections in the kidney for the first time. Destruction of LD-mitochondria connection was involved in renal lipid deposition in the kidneys of patients and mice with DN or in high-glucose-treated HK-2 cells. Furthermore, sesamol treatment significantly increased the integrity of the LD-mitochondria connection and ameliorated renal lipotoxicity. Finally, we demonstrated that sesamol maintains the integrity of the LD-mitochondria connection by activating the peroxisome proliferator-activated receptor α (PPARα)/perilipin 5 (PLIN5) signaling pathway. Our study is the first to show that the LD-mitochondria connection may be a target for ameliorating lipid deposition in diabetic kidneys.

Single-base m6A epitranscriptomics reveals novel HIV-1 host interaction targets in primary CD4+ T cells.

N 6-methyladenosine (m6A) is the most prevalent cellular mRNA modification and plays a critical role in regulating RNA stability, localization, and gene expression. m6A modification plays a vital role in modulating the expression of viral and cellular genes during HIV-1 infection. HIV-1 infection increases cellular RNA m6A levels in many cell types, which facilitates HIV-1 replication and infectivity in target cells. However, the function of m6A modification in regulating HIV-1 infection of primary CD4+ T cells remains unclear. Here, we demonstrate that HIV-1 infection of Jurkat CD4+ T cells and primary CD4+ T cells promotes the interaction between the m6A writer complex subunits methyltransferase-like 3 and 14 (METTL3/METTL14). Using single-base m6A-specific RNA sequencing, we identified several differentially m6A-modified cellular mRNAs, including perilipin 3 (PLIN3), during HIV-1 infection in primary CD4+ T cells. Interestingly, HIV-1 infection increased PLIN3 mRNA level by enhancing its stability, but PLIN3 protein level was decreased. Knocking down PLIN3 in primary CD4+ T cells reduced HIV-1 production but enhanced virion infectivity. In contrast, in Jurkat cells, PLIN3 mRNA and protein expression levels were unaffected by HIV-1 infection, and knocking out PLIN3 did not impact HIV-1 production or infectivity. These results indicate that the interplay between HIV-1 and PLIN3 is cell-type specific and only observed in primary CD4+ T cells. Overall, our results highlight the importance of m6A RNA modification in HIV-1-infected primary CD4+ T cells and suggest its significance as a regulatory mechanism in HIV-1 infection.

PLIN5 contributes to lipophagy of hepatic stellate cells induced by inorganic arsenic.

Arsenic exposure triggers the activation of hepatic stellate cells (HSCs), resulting in liver fibrosis (LF). A significant decrease in lipid droplets marks the activation of HSCs. However, the exact underlying molecular mechanism remains elusive. Lipophagy, a specialized form of selective autophagy, is crucial for the degradation of lipid droplets to maintain intracellular lipid metabolism homeostasis. In this study, arsenic treatment induced lipophagy, as evidenced by the co-localization of LC3 with lipid droplets. Remarkably, arsenic exposure increased the expression levels of Perilipin 5 (PLIN5), a lipid droplet-associated protein, both at the mRNA and protein levels. Moreover, silencing PLIN5 influenced arsenic-induced lipolysis. Consequently, the results of this study indicate that PLIN5 serves as a substrate protein involved in arsenic-induced lipophagy. This research offers a novel perspective on the mechanisms of arsenic-induced HSCs activation and liver lipid metabolism, potentially guiding new strategies for the prevention and treatment of arsenic-related liver diseases.

VPS28 regulates triglyceride synthesis via ubiquitination in bovine mammary epithelial cells

VPS28 (vacuolar protein sorting 28) is a subunit of the endosomal sorting complexes required for transport (ESCRTs) and is involved in ubiquitination. Ubiquitination is a critical system for protein degradation in eukaryotes. Considering the recent findings on the role of ubiquitination in the regulation of lipid metabolism, we hypothesized that VPS28 might affect the expression of genes involved in milk fat synthesis. To test this hypothesis, we modulated VPS28 expression in the bovine mammary epithelial cell line (MAC-T) and measured the effects on triglyceride (TG) synthesis using lentivirus-mediated techniques. The results showed that VPS28 knockdown significantly upregulated the levels of the fatty acid transporter CD36 molecule (CD36) and adipose differentiation-related protein (ADFP), leading to increased TG and fatty acid production, along with elevated ubiquitin (UB) levels, while reducing proteasome activity. In contrast, VPS28 overexpression increased CD36 levels while not significantly affecting ADFP or TG levels, with a trend toward reduced lipid droplets and increased UB expression and proteasome activity. In addition, inhibition of the ubiquitin-proteasome system and the endosomal-lysosomal pathway using epoxomicin and chloroquine, respectively, further increased CD36, ADFP, and TG levels, thereby enhancing cell viability. These in vitro findings were validated in vivo in a mouse model, where VPS28 knockdown increased mammary CD36, ADFP, UB expression, TG content, and lipid droplets without pathological changes in mammary tissue or blood TG alterations. These results confirm the pivotal role of VPS28 in regulating TG synthesis via the ubiquitination pathway, offering novel insights into the molecular mechanisms of milk fat production in a bovine cell model.

Profile of miRNAs induced during sheep fat tail development and roles of four key miRNAs in proliferation and differentiation of sheep preadipocytes.

The fat tail of sheep is an adaptive trait that facilitates their adaptation to harsh natural environments. MicroRNAs (miRNAs) have been demonstrated to play crucial roles in the regulation of tail fat deposition. In this study, miRNA-Seq was employed to investigate the expression profiles of miRNAs during different developmental stages of sheep fat tails and elucidate the functions of differentially expressed miRNAs (DE miRNAs). A total of 350 DE miRNAs were identified, among which 191, 60, 26, and 21 were significantly upregulated in tail fat tissues of fetal, lamb, hogget Altay sheep, and adult Xinjiang fine wool (XFW) sheep but downregulated in other stages. Furthermore, we predicted a set of candidate target genes (4,476) for the top 20 DE miRNAs. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that they involve in several adipogenesis-related pathways. Subsequent investigations indicated that four DE miRNAs, miR-433-3p, miR-485-3p, miR-409-3p, and miR-495-3p, could suppress the expression of peroxisome proliferator-activated receptor gamma (PPARγ) and phosphoinositide-3-kinase regulatory subunit 3 (PIK3R3) and regulate the preadipocyte development in sheep. Meanwhile, the lipid metabolism-related genes, fatty acid-binding protein (FABP3), perilipin 1 (PLIN1), adiponectin C1Q and collagen domain containing (ADIPOQ), and lipoprotein lipase (LPL), were significantly downregulated (p < 0.01). The expression patterns of miRNAs exhibited significant fluctuations during different development periods of the fat tail, and some of them may participate in the regulation of tail fat deposition by modulating the proliferation and differentiation of preadipocytes.

Accurate diagnosis of early-stage lung cancer by targeting lipid droplets with a two-photon near-infrared fluorescence probe

Clinically, solid nodules with adenocarcinoma (SN–ADC) exhibit faster growth and greater invasiveness than ground-glass nodules with adenocarcinoma (GGN-ADC). Metabolic reprogramming is a critical feature of tumor cells and may facilitate the rapid progression of early-stage lung cancer. Herein, we used laser microdissection to precisely isolate malignant regions from five SN–ADC and six GGN–ADC samples for proteomic analysis. Bioinformatic analysis, western blotting, and electron microscopy conducted in this study revealed a significant upregulation of lipid droplet-associated protein (PLIN2) and marked increase in lipid droplet (LD) accumulation in SN–ADC tissues. Consequently, a novel two-photon near-infrared fluorescence probe was developed to monitor the dynamic changes in LDs in lung cancer cells. Further, experimental validation confirmed the effectiveness of the LD probe (LD-probe) in monitoring the changes in LDs in tumor cells and distinguishing LD differences between tumor and normal tissues. In particular, the probe successfully detected significant differences in LD behavior between SN–ADC and GGN–ADC in early-stage lung cancer. Thus, this study developed a rapid and effective tool for the diagnosis of early-stage lung cancer. The proposed method offers deeper insight into the monitoring of the behavior of LDs in tumor cells, with potential clinical applications.

CT Characterization of Lipid Metabolism in Clear Cell Renal Cell Carcinoma: Relationship Between Liver Hounsfield Unit Values and Adipose Differentiation-Related Protein Gene Expression.

Radiogenomics is an emerging field that links imaging features with molecular characteristics of diseases. In clear cell renal cell carcinoma (ccRCC), metabolic reprogramming leads to lipid accumulation, influenced by the adipose differentiation-related protein (ADFP). This study aimed to investigate whether hepatic and tumoral Hounsfield Unit (HU) values could serve as noninvasive radiogenomic biomarkers for ADFP expression in ccRCC. We analyzed CT images of 185 ccRCC patients, comparing lipid-associated HU values in the liver and tumor across ADFP expression statuses. Patients with low-grade ccRCC expressing ADFP showed significantly lower minimum HU values in both liver and tumor tissue, indicating greater lipid accumulation. Additionally, ADFP expression correlated negatively with abdominal adipose tissue compartments and positively with minimum tumoral HU values, linking systemic lipid metabolism to tumor biology. These findings suggest that hepatic and tumoral HU measurements may serve as noninvasive markers of lipid accumulation related to ADFP, providing insight into metabolic alterations in ccRCC. While promising, these results require validation in larger, controlled studies due to sample size and variability limitations. This approach could enhance the radiogenomic assessment of ccRCC, supporting noninvasive insights into tumor metabolism and progression.

Advanced glycation end-products accelerate amyloid deposits in adipocyte's lipid droplets.

Adipose tissue dysfunction is central to insulin resistance, and the emergence of type 2 diabetes (T2D) is associated with elevated levels of carbonyl metabolites from glucose metabolism. In this study, using methylglyoxal (MGO) and glycolaldehyde (GAD) carbonyl metabolites induced protein glycation, leading to misfolding and β-sheet formation and generation of advanced glycation end products (AGEs). The formed AGEs compromise adipocytes activity. Microscopic and spectroscopic assays were used to examine the impact of MGO and GAD on lipid droplet-associated proteins. The results provide information about how these conditions lead to the appearance of glycated and amyloidogenic proteins formation that hinders metabolism and autophagy in adipocytes. We measured the beneficial effects of metformin (MET), an anti-diabetic drug, on misfolded protein as assessed by thioflavin (ThT) spectroscopy and improved autophagy, determined by LC3 staining. In vitro findings were complemented by in vivo analysis of white adipose tissue (WAT), where lipid droplet-associated β-amyloid deposits were predominantly linked to adipose triglyceride lipase (ATGL), a lipid droplet protein. Bioinformatics, imaging, biochemical and MS/MS methods affirm ATGL's glycation and its role in β-sheet secondary structure formation. Our results highlighted the pronounced presence of amyloidogenic proteins in adipocytes treated with carbonyl compounds, potentially reshaping our understanding of adipocyte altered activity in the context of T2D. This in-depth exploration offers novel perspectives on related pathophysiology and underscores the potential of adipocytes as pivotal therapeutic targets, bridging T2D, amyloidosis, protein glycation, and adipocyte malfunction.

The Prognostic Impact of Adipophilin Expression on Long-Term Survival Following Liver Resection in Patients with Colorectal Liver Metastases.

Background/Objectives: Adipophilin (ADP) is a protein associated with lipid droplets, and its expression is related to poor prognosis in certain cancers. However, its impact on the survival of patients with colorectal liver metastases (CRLMs) remains unclear. This study investigated the impact of ADP expression on long-term survival following hepatectomy in patients with CRLM. Methods: We retrospectively analyzed 102 consecutive patients who underwent hepatectomy between 2006 and 2022. ADP expression was examined in resected specimens through immunohistochemical staining using tissue microarrays. Long-term outcomes for ADP-positive (n = 51) and ADP-negative (n = 51) groups were compared with Kaplan-Meier survival analysis. Results: We found significantly decreased 5-year recurrence-free survival (RFS) and overall survival (OS) rates for ADP-positive patients relative to ADP-negative patients (29.4% versus 52.1%, respectively; p = 0.001 and 43.7% versus 72.2%, respectively; p = 0.003). Moreover, multivariate Cox hazards analysis demonstrated that patients with ADP-positive CRLM had a worse prognosis after hepatectomy than those with ADP-negative CRLM, as reflected by both RFS (HR 2.46, 95% CI 1.39-4.36, p = 0.002) and OS (HR: 2.89, 95% CI 1.43-5.85, p = 0.003). Conclusions: ADP expression had a significant prognostic impact on the survival of patients with CRLM following liver resection and may aid in optimal treatment planning.

Perilipin 5 Phosphorylation is Dispensable for Upregulation of Hepatic Lipid Metabolism Genes upon Fasting but Required for Insulin Receptor Substrate 2 Expression in Male Mice.

Perilipin 5 (PLIN5) is a lipid droplet protein highly expressed in cells that actively oxidize fatty acids. Previous in vitro studies have revealed that PLIN5 phosphorylation (p-PLIN5) at serine 155 by PKA is critical for transcriptional regulation of PPARa target genes by which PLIN5 adapt cells for fatty acid oxidation. We aim to determine the extent of p-PLIN5 in vivo and the consequence of impaired PLIN5 phosphorylation in the liver by using a whole-body knock-in of phosphorylation resistant PLIN5 (SA/SA) in mice. We measured PLIN5 and p-PLIN5 with mass spectrometry and Phos-tag gels. We assessed serum chemistry in WT and SA/SA mice upon fasting. RNA sequencing and qPCR compared the gene expression in the liver of SA/SA and WT mice after overnight fast. Plin5 phosphorylation at S155 was increased in the liver LD fraction of fasted mice compared with that of fed mice by mass spectrometry (p<0.05). qPCR of key lipid metabolism genes did not differ between WT and SA/SA liver upon fasting. Male SA/SA mice had a higher fasting blood glucose (p<0.05) without a difference in body weight, serum insulin, or serum lipids. IRS2 was reduced in the liver of fasted male SA/SA mice (p<0.05). PLIN5 S155 phosphorylation is dispensable for the upregulation of lipid metabolism genes important for fasting response in vivo. Impaired phosphorylation also had little effect on serum lipids or liver TG. However, SA/SA mice showed decreased IRS2 expression in the liver, which may contribute to glucose intolerance in SA/SA male mice.

Differential Plin5 response to high-fat diet in cardiomyocytes isolated from young and aged mice

This study investigates the differences in the heart response to an 8-week high-fat diet between young and aged mice. Isolated cardiomyocytes reveal a significant lower level in the lipid droplet-associated protein Plin5 in aged mice. High-fat diet, however, leads to an induction of Plin5 in aged mice and a low-response of lipid metabolism, whereas in cardiomyocytes from young animals the Plin5 level was largely unaffected by high-fat diet whereas several lipid metabolizing enzymes were induced. Therefore, the high-fat diet induced lipid droplet accumulation is more pronounced in cardiomyocytes isolated from aged animals.

A PLIN1 polymorphism is associated with fat production in male emus

The emu (Dromaius novaehollandiae) is a novel poultry species that produces meat, eggs, and fat. Although emus have recently been domesticated, genetic improvements to establish strains have scarcely progressed. In this study, we investigated the relationship between production traits and perilipin 1-encoding gene (PLIN1) polymorphisms in the emus. We determined the partial complementary DNA (cDNA) sequence of the PLIN1, which is involved in lipid droplet formation. We identified four nucleotide substitution sites (c.270C>T, c.321T>C, c.587A>T, and c.639C>T) in the PLIN1 gene of emus. Of these, c.587A>T is a non-synonymous substitution that converts lysine to methionine at the 196th codon (p.K196M). Although p.K196M was predicted to affect the production traits of emus, a large deflection in genotype frequency was observed in this study; thus, we could not investigate the relationship between genotypes and phenotypes. In males, the fat yields of the CC, CT, and TT genotypes in c.270C>T were 0.25 ± 0.06, 0.22 ± 0.06, and 0.21 ± 0.07 kg, respectively, while the meat yields of the CC, CT, and TT genotypes in c.270C>T were 0.15 ± 0.01, 0.16 ± 0.02, and 0.16 ± 0.03 kg, respectively. These results indicate that male emus with the CC genotype had a significantly higher fat content and lower meat productivity than male emus with the other genotypes (P < 0.05). Therefore, c.270C>T in PLIN1 affects fat and meat production in males. Our findings may contribute to the effective genetic improvement of the emus.

Lipid droplet-associated proteins in alcohol-associated fatty liver disease: A proteomic approach.

The earliest manifestation of alcohol-associated liver disease (ALD) is steatosis characterized by deposition of fat in specialized organelles called lipid droplets (LDs). While alcohol administration causes a rise in LD numbers in the hepatocytes, little is known regarding their characteristics that allow their accumulation and size to increase. The aim of the present study is to gain insights into underlying pathophysiological mechanisms by investigating the ethanol-induced changes in hepatic LD proteome as a function of LD size. Adult male Wistar rats (180-200 g BW) were fed with ethanol liquid diet for 6 weeks. At sacrifice, large-, medium-, and small-sized hepatic LD subpopulations (LD1, LD2, and LD3, respectively) were isolated and subjected to morphological and proteomic analyses. Morphological analysis of LD1-LD3 fractions of ethanol-fed rats clearly demonstrated that LD1 contained larger LDs compared with LD2 and LD3 fractions. Our preliminary results from principal component analysis showed that the proteome of different-sized hepatic LD fractions was distinctly different. Proteomic data analysis identified over 2000 proteins in each LD fraction with significant alterations in protein abundance among the three LD fractions. Among the altered proteins, several were related to fat metabolism, including synthesis, incorporation of fatty acid, and lipolysis. Ingenuity pathway analysis revealed increased fatty acid synthesis, fatty acid incorporation, LD fusion, and reduced lipolysis in LD1 compared to LD3. Overall, the proteomic findings indicate that the increased level of protein that facilitates fusion of LDs combined with an increased association of negative regulators of lipolysis dictates the generation of large-sized LDs during the development of alcohol-associated hepatic steatosis. Several significantly altered proteins were identified in different-sized LDs isolated from livers of ethanol-fed rats. Ethanol-induced increases in specific proteins that hinder LD lipid metabolism led to the accumulation and persistence of large-sized LDs in the liver.

The influence of perilipin 5 deficiency on gut microbiome profiles in murine metabolic dysfunction-associated fatty liver disease (MAFLD) and MAFLD-hepatocellular carcinoma.

Metabolic dysfunction-associated fatty liver disease (MAFLD) has emerged as the leading cause of hepatocellular carcinoma (HCC) worldwide. Over the years, Perilipin 5 (PLIN5) has been recognized as a key regulator of both MAFLD and HCC development. In our previous studies we demonstrated that deficiency in Plin5 reduces the severity of MAFLD and HCC in mice. Interestingly, it has been established that patients with MAFLD and HCC exhibit various changes in their gut microbiome profiles. The gut microbiome itself has been shown to play a role in modulating carcinogenesis and the immune response against cancer. Therefore, we conducted a study to investigate the alterations in fecal microbiome composition in wild type (WT) and Plin5-deficient (Plin5 -/-) mice models of MAFLD and MAFLD-induced HCC (MAFLD-HCC). We utilized 16S rRNA gene sequencing analysis to profile the composition of gut bacteria in fecal samples. Notably, we discovered that the absence of Plin5 alone is already associated with changes in gut microbiota composition. Moreover, feeding the mice a Western diet (WD) resulted in additional microbial alterations. Interestingly, Plin5 -/- animals exhibited an enrichment of the beneficial taxa Lactobacillus in both animal models. Our findings identify Plin5 as a major regulator of gut microbiota during the development of MAFLD and MAFLD-HCC.

Investigation of oral toxicity of WS2 nanosheets to mouse intestine: Pathological injury, trace element balance, lipid profile changes, and autophagy.

The success of graphene oxides has gained extensive research interests in developing novel 2D nanomaterials (NMs). WS2 nanosheets (NSs) are novel transition metal-based 2D NMs, but their toxicity is unclear. In this study, we investigated the oral toxicity of WS2 NSs to mouse intestines. Male mice were administrated with vehicles, 1, 10, or 100 mg/kg NSs via intragastric route, once a day, for 5days. The results indicate that the NSs did not induce pathological or ultrastructural changes in intestines. There were minimal changes of trace elements that the exposure did not induce W accumulation, and only Co levels were dose-dependently increased. Lipid droplets were observed in all groups of mice, but lipidomics data indicate that WS2 NSs only significantly decreased four lipid species, all belonging to phosphatidylcholine (PC). The levels of proteins regulating autophagic lipolysis, namely, LC3, lysosomal associated membrane protein 2 (LAMP2) and perilipin 2 (PLIN2), were increased, but it was only statistically significantly different for LC3. The results of this study suggest that repeated intragastric exposure to WS2 NSs only induced minimal influences on pathological injury, trace element balance, autophagy, and lipid profiles in mouse intestines, indicating relatively high biocompatibility of WS2 NSs to mouse intestine via oral route.

Surface tension-driven sorting of human perilipins on lipid droplets.

Perilipins (PLINs), the most abundant proteins on lipid droplets (LDs), display similar domain organization including amphipathic helices (AH). However, the five human PLINs bind different LDs, suggesting different modes of interaction. We established a minimal system whereby artificial LDs covered with defined polar lipids were transiently deformed to promote surface tension. Binding of purified PLIN3 and PLIN4 AH was strongly facilitated by tension but was poorly sensitive to phospholipid composition and to the presence of diacylglycerol. Accordingly, LD coverage by PLIN3 increased as phospholipid coverage decreased. In contrast, PLIN1 bound readily to LDs fully covered by phospholipids; PLIN2 showed an intermediate behavior between PLIN1 and PLIN3. In human adipocytes, PLIN3/4 were found in a soluble pool and relocated to LDs upon stimulation of fast triglyceride synthesis, whereas PLIN1 and PLIN2 localized to pre-existing LDs, consistent with the large difference in LD avidity observed in vitro. We conclude that the PLIN repertoire is adapted to handling LDs with different surface properties.

Dynamic Brain Lipid Profiles Modulate Microglial Lipid Droplet Accumulation and Inflammation Under Ischemic Conditions in Mice.

Microglia are critically involved in post-stroke inflammation affecting neurological outcomes. Lipid droplet (LD) accumulation in microglia results in a dysfunctional and pro-inflammatory state in the aged brain and worsens the outcome of neuroinflammatory and neurodegenerative diseases. However, the role of LD-rich microglia (LDRM) under stroke conditions is unknown. Using in vitro and in vivo stroke models, herein accumulation patterns of microglial LD and their corresponding microglial inflammatory signaling cascades are studied. Interactions between temporal and spatial dynamics of lipid profiles and microglial phenotypes in different post-stroke brain regions are found. Hence, microglia display enhanced levels of LD accumulation and elevated perilipin 2 (PLIN2) expression patterns when exposed to hypoxia or stroke. Such LDRM exhibit high levels of TNF-α, IL-6, and IL-1β as well as a pro-inflammatory phenotype and differentially expressed lipid metabolism-related genes. These post-ischemic alterations result in distinct lipid profiles with spatial and temporal dynamics, especially with regard to cholesteryl ester and triacylglycerol levels, further exacerbating post-ischemic inflammation. The present study sheds new light on the dynamic changes of brain lipid profiles and aggregation patterns of LD in microglia exposed to ischemia, demonstrating a mutual mechanism between microglial phenotype and function, which contributes to progression of brain injury.

Hypoxia-inducible lipid droplet-associated protein (HILPDA) and cystathionine β-synthase (CBS) co-contribute to protecting intestinal epithelial cells from Staphylococcus aureus via regulating lipid droplets formation

Despite Staphylococcus aureus (S. aureus) being a highly studied zoontic bacterium, its enteropathogenicity remains elusive. Herein, our findings demonstrated that S. aureus infection led to the accumulation of lipid droplets (LDs) in intestinal epithelial cells, accompanied by marked elevation inflammatory response that ultimately decreases intracellular bacterial load. The aforestated phenomenon may be partly attributed to the up-regulation of hypoxia-inducible lipid droplet-associated protein (HILPDA) and the concomitant down-regulation of cystathionine β-synthase (CBS) protein. Moreover, S. aureus infection up-regulated the expression of HILPDA, thereby promoting LDs accumulation, and down-regulated that of CBS, consequently inhibiting microsomal triglyceride transfer protein (MTTP) expression. This process may suppress the transport of LDs to the extracellular environment, further contributing to the formation of intracellular LDs. In summary, the results of this study provide significant insights into the intricate mechanisms through which the host organism combats pathogens and maintains the balance of sulfur and lipid metabolism. These findings not only enhance our understanding of the host's defense mechanisms but also offer promising avenues for the development of novel strategies to combat intestinal infectious diseases.