Palmitic acid up regulates Gal‑3 and induces insulin resistance in macrophages by mediating the balance between KLF4 and NF‑κB

Jing, Li; Mao, Yu; Chen, Fen; Xia, Dongxia; Zhao, Tin-Qi

doi:10.3892/etm.2021.10460

Cited by 7 publications

(4 citation statements)

References 45 publications

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“…It would also be prudent to investigate whether LDs formation is involved in POA lipoprotection via perilipin knockdown. Galectin-3 expression has also been shown to be significantly upregulated in PA-induced macrophages, consistent with the results of this study [39]. The aggregation of galectin-3 further suggests that PA leads to the rupture of lysosomes.…”

Section: Plos Onesupporting

confidence: 91%

Palmitoleic acid protects microglia from palmitate-induced neurotoxicity in vitro

Yu,

Yang,

et al. 2024

PLoS ONE

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Although palmitoleic acid (POA) is a lipokine with beneficial effects on obesity and is produced as a byproduct from the manufacture of prescription omega-3 fatty acids, its role in nervous system inflammation is still unknown. This study aims to examine the mechanisms and protective effects of POA against palmitic acid (PA)-induced microglial death. PA-induced microglial death was used as a model for POA intervention. Various inhibitors were employed to suppress potential routes of PA entry into the cell. Immunofluorescence staining and Western blotting were conducted to elucidate the protective pathways involved. The results suggest POA has the potential to eliminate PA-induced lactate dehydrogenase (LDH) release, which decreases the overall number of propidium iodide (PI)-positive cells compared with control. Moreover, POA has the potential to significantly increase lipid droplets (LDs) in the cytoplasm, without causing any lysosomal damage. POA inhibited both canonical and non-canonical gasdermin D (GSDMD)-mediated pyroptosis and gasdermin E (GSDME)-mediated pyroptosis, which PA typically induces. Additionally, POA inhibited the endoplasmic reticulum (ER) stress and apoptosis-related proteins induced by PA. Based on the findings, POA can exert a protective effect on microglial death induced by PA via pathways related to pyroptosis, apoptosis, ER stress, and LDs.

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Section: Plos Onesupporting

confidence: 91%

Palmitoleic acid protects microglia from palmitate-induced neurotoxicity in vitro

Yu,

Yang,

et al. 2024

PLoS ONE

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“…GADD45B can be used as a prognostic biomarker in the diagnosis of DN, 35 and it has been proved that the expression of GADD45B is downregulated in synovial tissue of OA 36 . KLF4 can inhibit inflammation and bone destruction in OA, 37 and inhibition of KLF4 expression can promote the conduction of the NF‐kB signal pathway and then improve the insulin resistance of macrophages 38 . Two genes (RASIP1 and PENK) have been reported to be related to T2DM.…”

Section: Discussionmentioning

confidence: 99%

“…36 KLF4 can inhibit inflammation and bone destruction in OA, 37 and inhibition of KLF4 expression can promote the conduction of the NF-kB signal pathway and then improve the insulin resistance of macrophages. 38 Two genes (RASIP1 and PENK) have been reported to be related to T2DM.…”

Section: Bayesian Co-localization Analysismentioning

confidence: 99%

Identification of the shared genes in type 2 diabetes mellitus and osteoarthritis and the role of quercetin

Song,

2024

J Cellular Molecular Medi

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This study investigated the underlying comorbidity mechanism between type 2 diabetes mellitus (T2DM) and osteoarthritis (OA), while also assessing the therapeutic potential of quercetin for early intervention and treatment of these two diseases. The shared genes were obtained through GEO2R, limma and weighted gene co‐expression network analysis (WGCNA), and validated using clinical databases and the area under the curves (ROC). Functional enrichment analysis was conducted to elucidate the underlying mechanisms of comorbidity between T2DM and OA. The infiltration of immune cells was analysed using the CIBERSORT algorithm in conjunction with ESTIMATE algorithm. Subsequently, transcriptional regulation analysis, potential chemical prediction, gene‐disease association, relationships between the shared genes and ferroptosis as well as immunity‐related genes were investigated along with molecular docking. We identified the 12 shared genes (EPHA3, RASIP1, PENK, LRRC17, CEBPB, EFEMP2, UBAP1, PPP1R15A, SPEN, MAFF, GADD45B and KLF4) across the four datasets. Our predictions suggested that targeting these shared genes could potentially serve as therapeutic interventions for both T2DM and OA. Specifically, they are involved in key signalling pathways such as p53, IL‐17, NF‐kB and MAPK signalling pathways. Furthermore, the regulation of ferroptosis and immunity appears to be interconnected in both diseases. Notably, in this context quercetin emerges as a promising drug candidate for treating T2DM and OA by specifically targeting the shared genes. We conducted a bioinformatics analysis to identify potential therapeutic targets, mechanisms and drugs for T2DM and OA, thereby offering novel insights into molecular therapy for these two diseases.

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“…Moreover, Gal-3 is also believed to exhibit pro-inflammatory properties [ 123 , 124 , 125 ]. In animal studies, the administration of Gal-3 contributed to glucose intolerance and insulin resistance, whereas the addition of its inhibitor reversed the effect [ 126 ].…”

Section: Galectin-3mentioning

confidence: 99%

Review of Novel Potential Insulin Resistance Biomarkers in PCOS Patients—The Debate Is Still Open

Kruszewska

Laudy-Wiaderny²,

Kunicki

2022

IJERPH

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Research on proteins and peptides that play roles in metabolic regulation, which may be considered potential insulin resistance markers in some medical conditions, such as diabetes mellitus, obesity and polycystic ovarian syndrome (PCOS), has recently gained in interest. PCOS is a common endocrine disorder associated with hyperandrogenemia and failure of ovulation, which is often accompanied by metabolic abnormalities, including obesity, dyslipidemia, hyperinsulinemia, and insulin resistance. In this review, we focus on less commonly known peptides/proteins and investigate their role as potential biomarkers for insulin resistance in females affected by PCOS. We summarize studies comparing the serum fasting concentration of particular agents in PCOS individuals and healthy controls. Based on our analysis, we propose that, in the majority of studies, the levels of nesfastin-1, myonectin, omentin, neudesin were decreased in PCOS patients, while the levels of the other considered agents (e.g., preptin, gremlin-1, neuregulin-4, xenopsin-related peptide, xenin-25, and galectin-3) were increased. However, there also exist studies presenting contrary results; in particular, most data existing for lipocalin-2 are inconsistent. Therefore, further research is required to confirm those hypotheses, as well as to elucidate the involvement of these factors in PCOS-related metabolic complications.

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Palmitic acid up regulates Gal‑3 and induces insulin resistance in macrophages by mediating the balance between KLF4 and NF‑κB

Cited by 7 publications

References 45 publications

Palmitoleic acid protects microglia from palmitate-induced neurotoxicity in vitro

Palmitoleic acid protects microglia from palmitate-induced neurotoxicity in vitro

Identification of the shared genes in type 2 diabetes mellitus and osteoarthritis and the role of quercetin

Review of Novel Potential Insulin Resistance Biomarkers in PCOS Patients—The Debate Is Still Open

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