CD36 Levels Research Articles

Neuroprotective Roles of Lauric Acid and Resveratrol: Shared Benefits in Neuroinflammation and Anxiety, Distinct Effects on Memory Enhancement

ABSTRACTNeuroinflammation can be triggered by a high‐fat/high‐fructose diet (HFFD), and CD36 may be an underlying mechanism. Lauric acid (LA), the major fatty acid in coconut oil, and resveratrol, the plant‐based polyphenolic compound, may exert anti‐inflammatory effects. Therefore, this study investigated the possible effects of LA and resveratrol on diet‐induced neuroinflammation and CD36. Healthy male C57BL/6 mice (8 weeks of age, n = 31) were fed a control diet (10%kcal fat) or diets containing high fat (60%kcal fat) and fructose (5% w/v fructose drinking water) for 6 weeks, ad libitum. Supplemented to the HFFD, mice daily received resveratrol (7.5 mg/kg) (HFFD‐RSV) or LA (750 mg/kg) (HFFD‐LA). At the end of the study, HFFD resulted in anxiety‐like behavior, reduced locomotor activity, neuroinflammation (increased brain GFAP, IL‐6, MCP‐1, IFN‐γ, TNF‐α), and systemic inflammation (increased plasma GFAP, IFN‐γ, TNF‐α, IL‐12p70, reduced plasma IL‐10). HFFD‐RSV and HFFD‐LA alleviated HFFD‐induced anxiety‐like behavior, neuroinflammation, and systemic inflammation. HFFD‐LA improved memory. Brain and plasma CD36 levels were increased by HFFD and reduced by HFFD‐RSV or HFFD‐LA. Dietary resveratrol and LA intake may alleviate HFFD‐induced neuroinflammation, systemic inflammation, and anxiety‐like behavior and improve memory, as CD36 may be an underlying mechanism.

Expression Profiles of Fatty Acid Transporters and the Role of n-3 and n-6 Polyunsaturated Fatty Acids in the Porcine Endometrium.

Fatty acids (FAs) are important for cell membrane composition, eicosanoid synthesis, and metabolic processes. Membrane proteins that facilitate FA transport into cells include FA translocase (also known as CD36) and FA transporter proteins (encoded by SLC27A genes). The present study aimed to examine expression profiles of FA transporters in the endometrium of cyclic and early pregnant gilts on days 3 to 20 after estrus and the possible regulation by conceptus signals and polyunsaturated FAs (PUFAs). The effect of PUFAs on prostaglandin (PG) synthesis and transcript abundance of genes related to FA action and metabolism, angiogenesis, and immune response was also determined. Day after estrus and reproductive status of animals affected FA transporter expression, with greater levels of CD36, SLC27A1, and SLC27A4 observed in pregnant than in cyclic gilts. Conceptus-conditioned medium and/or estradiol-17β stimulated SLC27A1 and CD36 expression. Among PUFAs, linoleic acid decreased SLC27A1 and SLC27A6 mRNA expression, while arachidonic, docosahexaenoic, and eicosapentaenoic acids increased SLC27A4 transcript abundance. Moreover, arachidonic acid stimulated ACOX1, CPT1A, and IL1B expression and increased PGE2 and PGI2 secretion. In turn, α-linolenic acid up-regulated VEGFA, FGF2, FABP4, and PPARG mRNA expression. These results indicate the presence of an active transport of FAs in the porcine endometrium and the role of PUFAs as modulators of the uterine activity during conceptus implantation.

The effect and mechanism of exposure to polystyrene nanoplastics on lipid metabolism in mice liver

Objective: To investigate the effect and potential mechanism of exposure to 20 nm polystyrene nanoplastics (PS-NPs) on lipid metabolism in mice liver. Methods: An animal experimental model was designed, which was completed from September 2022 to July 2023 on the exposure omics platform of the School of Public Health at Capital Medical University and the Key Laboratory of Environment and Population Health at the Chinese Center for Disease Control and Prevention.1 mg/kg and 10 mg/kg PS-NPs tail vein mice exposure models were constructed. After exposure 7 d, serum was collected to measure the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and air flow assisted desorption electrospray ionization-mass spectrometry imaging (AFADESI-MSI) analysis were used to analyze the mRNA levels of fatty acid esterification related genes (Dgat1 and Dgat2) and lipid transport related genes (ApoB, Cd36, ApoE and Mttp) and metabolites' spatial changes in liver tissue. In vivo imaging system (IVIS) and tissue shake sections were employed to observe the fluorescence biological distribution of PS-NPs. t-test or one-way ANOVA was used to explore the difference between groups. Results: The serum ALT levels were (83.97±4.58), (91.17±13.69) and (142.43±6.09) U/L in the control group, 1 mg/kg PS-NPs exposure group and 10 mg/kg PS-NPs exposure group respectively (F=37.281, P<0.05). The relative mRNA levels of Dgat1, Dgat2, ApoB, Cd36 and ApoE were (1.49±0.63, 2.53±0.32, 2.45±0.54), (1.07±0.38, 1.86±0.83, 2.23±0.73), (1.01±0.13, 1.58±0.43, 2.03±0.52), (1.01±0.14, 1.55±0.37, 1.52±0.51), (1.01±0.17, 2.11±0.27, 2.39±0.93) in these three groups respectively. The differences were statistically significant (F=11.54, 6.95, 14.90, 5.98 and 14.68, P<0.05). AFADESI-MSI analysis found that PS-NPs exposure led to a significant decrease in the levels of glutarylcarnitine and O-Linoleoylcarnitine (t=4.12 and 3.35, P<0.05), which were associated with lipid beta oxidation. The content of triglycerides (TG) (m/z 921.726 4, t=8.69, P<0.05; m/z 919.711 4, t=3.20, P<0.05), phosphatidylic acid (PA) (m/z 895.712 3, t=3.60, P<0.05; m/z 821.526 6, t=3.36, P<0.05), lysophosphatidylcholine (LysoPC) (m/z 560.310 6, t=3.35, P<0.05; m/z 582.295 3, t=6.28, P<0.05), phosphatidylcholine (PC) (m/z 778.533 9, t=3.53, P<0.05; m/z 804.549 6, t=3.60, P<0.05; m/z 820.523 1, t=3.37, P<0.05), phosphatidylethanolamine (PE) (m/z 772.523 3, t=3.08, P<0.05) showed a significant increase in the PS-NPs exposure group. In vivo and in vitro imaging and in situ cell localization revealed that PS-NPs were mainly enriched in hepatic stellate cells and hepatic Kupffer cells in liver tissue. Conclusion: Exposure to PS-NPs induces disorder of liver lipid metabolism, which may be related to the accumulation of PS-NPs in hepatic stellate cells and hepatic Kupffer cells, providing basis for searching early biomarkers of PS-NPs exposure and further mechanism research.

ADAMTS7 Promotes Smooth Muscle Foam Cell Expansion in Atherosclerosis.

Human genetic studies have repeatedly associated ADAMTS7 with atherosclerotic cardiovascular disease. Subsequent investigations in mice demonstrated that ADAMTS7 is proatherogenic and induced in response to vascular injury and that the proatherogenicity of ADAMTS7, a secreted protein, is due to its catalytic activity. However, the cell-specific mechanisms governing ADAMTS7 proatherogenicity remain unclear. To determine which vascular cell types express ADAMTS7, we interrogated single-cell RNA sequencing of human carotid atherosclerosis and found ADAMTS7 expression in smooth muscle cells (SMCs), endothelial cells (ECs), and fibroblasts. We subsequently created SMC- and EC-specific Adamts7 conditional knockout and transgenic mice. Conditional knockout of Adamts7 in either cell type is insufficient to reduce atherosclerosis, whereas transgenic induction in either cell type increases atherosclerosis. In SMC transgenic mice, this increase coincides with an expansion of lipid-laden SMC foam cells and decreased fibrous cap formation. RNA-sequencing in SMCs revealed an upregulation of lipid uptake genes typically assigned to macrophages. Subsequent experiments demonstrated that ADAMTS7 increases SMC oxLDL uptake through increased CD36 levels. Furthermore, Cd36 expression is increased due to increased levels of PU.1, a transcription factor typically associated with myeloid fate determination. In summary, Adamts7 expression in either SMCs or ECs promotes SMC foam cell formation and atherosclerosis. In SMCs, ADAMTS7 promotes oxLDL uptake via increased PU.1 and Cd36 expression, thereby increasing SMC foam cell formation and atherosclerosis.

SUN1 inhibits osteogenesis and promotes adipogenesis of human adipose-derived stem cells by regulating α-tubulin and CD36 expression.

Sad and UNC84 domain 1 (SUN1) is a kind of nuclear envelope protein with established involvement in cellular processes, including nuclear motility and meiosis. SUN1 plays an intriguing role in human adipose-derived stem cells (hASCs) differentiation; however, this role remains largely undefined. This study was undertaken to investigate the role of SUN1 in hASCs differentiation, as well as its underlying mechanisms. Employing siRNAs, we selectively downregulated SUN1 and CD36 expression. Microtubules were depolymerized using nocodazole, and PPARγ was activated using rosiglitazone. Western blotting was performed to quantify SUN1, PPARγ, α-tubulin, CD36, OPN, and adiponectin protein expression levels. Alkaline phosphatase and Oil red O staining were used to assess osteogenesis and adipogenesis, respectively. Downregulated SUN1 expression increased osteogenesis and decreased adipogenesis in hASCs, concomitant with upregulated α-tubulin expression and downregulated CD36 expression, alongside reduced nuclear localization of PPARγ. Microtubule depolymerization increased CD36 expression. Rescue experiments indicated that microtubule depolymerization counteracted the downregulated SUN1-induced phenotypic changes. This study demonstrates that SUN1 influences the differentiation of hASCs towards osteogenic and adipogenic lineages, indicating its essential role in cell fate.

Involvement of the AMPK Pathways in Muscle Development Disparities across Genders in Muscovy Ducks.

The differences in muscle development potential between male and female ducks lead to variations in body weight, significantly affecting the growth of the Muscovy duck meat industry. The aim of this study is to explore the regulatory mechanisms for the muscle development differences between genders. Muscovy ducks of both sexes were selected for measurements of body weight, growth traits, hormone levels, and muscle gene expression. The results show that male ducks compared to females had greater weight and growth traits (p < 0.05). Compared to male ducks, the level of serum testosterone in female ducks was decreased, and the estradiol levels were increased (p < 0.05). The RNA-seq analysis identified 102 upregulated and 49 downregulated differentially expressed genes. KEGG analysis revealed that among the top 10 differentially enriched pathways, the AMPK signaling pathway is closely related to muscle growth and development. Additionally, the mRNA and protein levels of CD36, CPT1A, LPL, and SREBP1 were increased and the P-AMPK protein level decreased in the female ducks compared to the male ducks (p < 0.05). In conclusion, muscle development potential difference between male and female ducks is regulated by sex hormones. This process is likely mediated through the activation of the AMPK pathway.

Fish Oil Replacement with Virgin Coconut and Corn Oil: Impact on Growth Performance, Lipogenic and Digestive Enzyme Activity, and mRNA Expression of Genes Involved in Lipid Metabolism of Nile tilapia (Oreochromis niloticus)

In relation to mRNA expressions, digestive and hepatic enzyme activity, growth performances of O. niloticus (6.07±0.07) was evaluated after feeding 56 days. Fish were fed six (6) experimental diets where fish oil (FO) supplements dietary oils; virgin coconut oil (VO) {3%FO+3%VO; FVO}, and corn oil (CO) {3%FO+3%CO; FCO}, 6%VO (VO), 6%CO (CO) and 6%VCO {3%VO+3%CO; VCO}. Those fed FCO recorded higher WG (1334.10±5.53) and SGR (4.76±0.01). Muscle lipid was significantly higher in group VO than CO and VCO whereas, it was significantly lower in the liver than the control group (P˂0.05). Dietary alternatives influenced digestive activities (amylase, lipase and trypsin) of which significant differences were not obtained between sections. Digestive enzymes lipase and pepsin were not significantly different at the posterior intestine. Liver receptors (FABP4 and PPAR-α) involved in fatty acid (FA) transport was not influenced, unlike CD36, G6PD and 6PGD. Although, the expression of PPAR-α gene was not different between groups, with the exception of group VCO, all other groups had no significant difference in expression levels of CD36, G6PD and 6PGD unlike FABP4. The study confirms that dietary vegetable lipids in partial replacement improve growth performances and maintain fish physiological functioning with preferences for utilization of 18: 3n-3 and 18: n-n9. Enzyme activity also positively correlates with growth rates and indicates good lipid metabolic activities and retention. As such, dietary alternatives influence liver enzyme activity and their mRNA expressions.

Propagermanium as a Novel Therapeutic Approach for the Treatment of Endothelial Dysfunction in Type 2 Diabetes.

Propagermanium (PG) has immune modulating activity and anti-inflammatory properties. This work aimed to study the therapeutic efficacy of PG on endothelial and perivascular dysfunction associated with type 2 diabetes. Non-obese type 2 diabetic Goto-Kakizaki (GK) rats were divided into four groups: (1) the control group; (2) the group treated with 50 mg/kg PG; (3) the group fed a high-fat diet (GKHFD); and (4) the group of GKHFD treated with 50 mg/kg PG. PG was given orally for 3 months. Several in vivo parameters and endothelial function were studied in aortas with perivascular adipose tissue PVAT (+) or without PVAT (-). We also determined the vascular inflammation and levels of CD36 in PVAT. In diabetic GK rats, PG did not affect the lipid profile or the results of the intraperitoneal glucose tolerance test. Instead, it improved the fasting glucose levels (18%, p < 0.01), insulin resistance (32%, p < 0.05), endothelial function (33 and 25% in aortas mounted with (+) or without PVAT (-), p < 0.05), and restored the anticontractile effect of the perivascular adipose tissue by reducing its inflammation (56%, p < 0.05) and oxidative stress profile (55%, p < 0.05). Due to its anti-inflammatory characteristics, PG likely improved endothelial dysfunction and restored the perivascular adipose tissue's anticontractile properties.

Age-related alteration of the involvement of CD36 for salivary secretion from the parotid gland in mice

This in vivo mouse model study was conducted to investigate the temporal alteration of the function of CD36 in salivary secretion. CD36 was highly expressed in the parotid gland of BALB/c mice. No significant variations were shown in the CD36 levels in the 8-, 48-, and 72-week-old animals. However, pilocarpine-induced salivary secretion was reduced in an age-dependent manner, showing a significantly low level at the age of 72 weeks. Pilocarpine-induced salivary secretion was significantly reduced by pretreatment with a CD36 inhibitor at 8 and 48 weeks, but not at 72 weeks. In senescence-accelerated mice (SAM), the pilocarpine-induced salivary secretion was significantly reduced at the age of 56 weeks, and a significantly lower amount of CD36 was demonstrated in the parotid gland, compared with the control. These results suggest that the involvement of parotid CD36 in mouse salivary secretion is altered with age.

Melanoma-Derived Extracellular Vesicles Induce CD36-Mediated Pre-Metastatic Niche.

CD36 expression in both immune and non-immune cells is known to be directly involved in cancer metastasis. Extracellular vesicles (EVs) secreted by malignant melanocytes play a vital role in developing tumor-promoting microenvironments, but it is unclear whether this is mediated through CD36. To understand the role of CD36 in melanoma, we first analyzed the SKCM dataset for clinical prognosis, evaluated the percentage of CD36 in lymphatic fluid-derived EVs (LEVs), and tested whether melanoma-derived EVs increase CD36 expression and induce M2-macrophage-like characteristics. Furthermore, we performed a multiplex immunofluorescence (MxIF) imaging analysis to evaluate the CD36 expression and its colocalization with various other cells in the lymph node (LN) of patients and control subjects. Our findings show that cutaneous melanoma patients have a worse clinical prognosis with high CD36 levels, and a higher percentage of CD36 in total LEVs were found at baseline in melanoma patients compared to control. We also found that monocytic and endothelial cells treated with melanoma EVs expressed more CD36 than untreated cells. Furthermore, melanoma-derived EVs can regulate immunosuppressive macrophage-like characteristics by upregulating CD36. The spatial imaging data show that cells in tumor-involved sentinel LNs exhibit a higher probability of CD36 expression than cells from control LNs, but this was not statistically significant. Conclusively, our findings demonstrated that CD36 plays a vital role in controlling the immunosuppressive microenvironment in the LN, which can promote the formation of a protumorigenic niche.

Proteome-wide analysis identifies plasma immune regulators of amyloid-beta progression

While immune function is known to play a mechanistic role in Alzheimer’s disease (AD), whether immune proteins in peripheral circulation influence the rate of amyloid-β (Aβ) progression – a central feature of AD – remains unknown. In the Baltimore Longitudinal Study of Aging, we quantified 942 immunological proteins in plasma and identified 32 (including CAT [catalase], CD36 [CD36 antigen], and KRT19 [keratin 19]) associated with rates of cortical Aβ accumulation measured with positron emission tomography (PET). Longitudinal changes in a subset of candidate proteins also predicted Aβ progression, and the mid- to late-life (20-year) trajectory of one protein, CAT, was associated with late-life Aβ-positive status in the Atherosclerosis Risk in Communities (ARIC) study. Genetic variation that influenced plasma levels of CAT, CD36 and KRT19 predicted rates of Aβ accumulation, including causal relationships with Aβ PET levels identified with two-sample Mendelian randomization. In addition to associations with tau PET and plasma AD biomarker changes, as well as expression patterns in human microglia subtypes and neurovascular cells in AD brain tissue, we showed that 31 % of candidate proteins were related to mid-life (20-year) or late-life (8-year) dementia risk in ARIC. Our findings reveal plasma proteins associated with longitudinal Aβ accumulation, and identify specific peripheral immune mediators that may contribute to the progression of AD pathophysiology.

LncRNA DANCR promotes macrophage lipid accumulation through modulation of membrane cholesterol transporters.

The progression of atherosclerosis (AS), the pathological foundation of coronary artery disease (CAD), is featured by massive lipid deposition in the vessel wall. LncRNAs are implicated in lipid disorder and AS, whereas the specific role of lncRNA DANCR in atherogenesis remains unknown. Here, we demonstrated that DANCR promotes macrophage lipid accumulation by regulating the expression of membrane cholesterol transport proteins. qPCR showed that compared to control groups, CAD patients and atherosclerotic mice had higher DANCR levels. Treating human THP-1 macrophages and mouse RAW264.7 macrophages with ox-LDL significantly upregulated the expression levels of DANCR. Oil Red O staining showed that the silence of DANCR robustly reduced, while overexpression of DANCR significantly increased the numbers and size of lipid droplets in ox-LDL-treated THP-1 macrophages. In contrast, the opposite phenomena were observed in DANCR overexpressing cells. The expression of ABCA1, ABCG1, SR-BI, and NBD-cholesterol efflux was increased obviously by DANCR inhibition and decreased by DANCR overexpression, respectively. Furthermore, transfection with DANCR siRNA induced a robust decrease in the levels of CD36, SR-A, and Dil-ox-LDL uptake, while DANCR overexpression amplified the expression of CD36, SR-A and the uptake of Dil-ox-LDL in lipid-laden macrophages. Lastly, we found that the effects of DANCR on macrophage lipid accumulation and the expression of membrane cholesterol transport proteins were not likely related to miR-33a. The present study unraveled the adverse role of DANCR in foam cell formation and its relationship with cholesterol transport proteins. However, the competing endogenous RNA network underlying these phenomena warrants further exploration.

Pantothenic Acid Alleviates Fat Deposition and Inflammation by Suppressing the JNK/P38 MAPK Signaling Pathway.

Excessive fat deposition leads to obesity and cardiovascular diseases with abnormal metabolism. Pantothenic acid (PA) is a major B vitamin required for energy metabolism. However, the effect of PA on lipid metabolism and obesity has not been explored. We investigated the effects and molecular mechanism of PA on fat accumulation as well as the influence of adipogenic marker genes in both adult male mice and primary adipocytes. First, we demonstrated that PA attenuates weight gain in mice fed high-fat diet (HFD). Besides, PA supplementation substantially improved glucose tolerance and lipid metabolic disorder in obese mice. Furthermore, PA significantly inhibited white adipose tissue (WAT) deposition as well as fat droplets visualized by magnification in both chow and HFD group. More importantly, PA obviously suppressed the mRNA levels of CD36, IL-6, and TNF-α to alleviate inflammation and reduced the levels of PPARγ, aP2, and C/EBPα genes that are related to lipid metabolism in inguinal white adipose tissue (ing-WAT) and epididymal white adipose tissue (ei-WAT). In vitro, PA supplementation showed a lower lipid droplet aggregation as well as reduced expression levels of adipogentic genes. Finally, we identified that PA inhibits the phosphorylation levels of p38 and JNK in murine primary adipocytes. Collectively, our data demonstrated for the first time that PA attenuates lipid metabolic disorder as well as fat deposition by JNK/p38 MAPK signaling pathway.

The mechanism of SSO regulating SiO(2)-induced lipid metabolism disorders in macrophages was explored based on lipid metabolomics

Objective: To investigate the mechanism of Sulfo-N-succinimidyloleate (SSO) regulating lipid metabolism disorder induced by silicon dioxide (SiO(2)) . Methods: In March 2023, Rat alveolar macrophages NR8383 were cultured in vitro and randomly divided into control group (C), SSO exposure group (SSO), SiO(2) exposure group (SiO(2)) and SiO(2)+SSO exposure group (SiO(2)+SSO). NR8383 cells were exposure separately or jointly by SSO and SiO(2) for 36 h to construct cell models. Immunofluorescence and BODIPY 493/ 503 staining were used to detect cluster of differentiation (CD36) and intracellular lipid levels, the protein expression levels of CD36, liver X receptors (LXR), P-mammalian target of rapamycin (P-mTOR) and cholinephosphotransferase 1 (CHPT1) were detected by Western blot, respectively, and lipid metabolomics was used to screen for different lipid metabolites and enrichment pathways. Single-factor ANOVA was used for multi-group comparison, and LSD test was used for pair-to-group comparison. Results: SiO(2) caused the expression of CD36 and P-mTOR to increase (P=0.012, 0.020), the expression of LXR to decrease (P=0.005), and the intracellular lipid level to increase. After SSO treatment, CD36 expression decreased (P=0.023) and LXR expression increased (P=0.000) in SiO(2)+SSO exposure group compared with SiO(2) exposure group. Metabolomics identified 87 different metabolites in the C group and SiO(2) exposure group, 19 different metabolites in the SiO(2) exposure group and SiO(2)+SSO group, and 5 overlaps of different metabolites in the two comparison groups, they are PS (22∶1/14∶0), DG (O-16∶0/18∶0/0∶0), PGP (i-13∶0/i-20∶0), PC (18∶3/16∶0), and Sphinganine. In addition, the differential metabolites of the two comparison groups were mainly concentrated in the glycerophospholipid metabolism and sphingolipid metabolism pathways. The differential gene CHPT1 in glycerophospholipid metabolic pathway was verified, and the expression of CHPT1 decreased after SiO(2) exposure. Conclusion: SSO may improve SiO(2)-induced lipid metabolism disorders by regulating PS (22∶1/14∶0), DG (O-16∶0/18∶0/0∶0), PGP (i-13∶0/i-20∶0), PC (18∶3/16∶0), SPA, glycerophospholipid metabolism and sphingolipid metabolism pathways.

Effects of emulsifiers on lipid metabolism and performance of yellow-feathered broilers

BackgroundReducing production costs while producing high-quality livestock and poultry products is an ongoing concern in the livestock industry. The addition of oil to livestock and poultry diets can enhance feed palatability and improve growth performance. Emulsifiers can be used as potential feed supplements to improve dietary energy utilization and maintain the efficient productivity of broilers. Therefore, further investigation is warranted to evaluate whether dietary emulsifier supplementation can improve the efficiency of fat utilization in the diet of yellow-feathered broilers. In the present study, the effects of adding emulsifier to the diet on lipid metabolism and the performance of yellow-feathered broilers were tested. A total of 240 yellow-feasted broilers (21-day-old) were randomly divided into 4 groups (6 replicates per group, 10 broilers per replicate, half male and half female within each replicate). The groups were as follows: the control group (fed with basal diet), the group fed with basal diet supplemented with 500 mg/kg emulsifier, the group fed with a reduced oil diet (reduced by 1%) supplemented with 500 mg/kg emulsifier, and the group fed with a reduced oil diet supplemented with 500 mg/kg emulsifier. The trial lasted for 42 days, during which the average daily feed intake, average daily gain, and feed-to-gain ratio were measured. Additionally, the expression levels of lipid metabolism-related genes in the liver, abdominal fat and each intestinal segment were assessed.ResultsThe results showed that compared with the basal diet group, (1) The average daily gain of the basal diet + 500 mg/kg emulsifier group significantly increased (P < 0.05), and the half-even-chamber rate was significantly increased (P < 0.05); (2) The mRNA expression levels of Cd36, Dgat2, Apob, Fatp4, Fabp2, and Mttp in the small intestine were significantly increased (P < 0.05). (3) Furthermore, liver TG content significantly decreased (P < 0.05), and the mRNA expression level of Fasn in liver was significantly decreased (P < 0.05), while the expression of Apob, Lpl, Cpt-1, and Pparα significantly increased (P < 0.05). (4) The mRNA expression levels of Lpl and Fatp4 in adipose tissue were significantly increased (P < 0.05), while the expression of Atgl was significantly decreased (P < 0.05). (5) Compared with the reduced oil diet group, the half-evading rate and abdominal fat rate of broilers in the reduced oil diet + 500 mg/kg emulsifier group were significantly increased (P < 0.05), and the serum level of LDL-C increased significantly (P < 0.05)0.6) The mRNA expression levels of Cd36, Fatp4, Dgat2, Apob, and Mttp in the small intestine were significantly increased (P < 0.05). 7) The mRNA expression levels of Fasn and Acc were significantly decreased in the liver (P < 0.05), while the mRNA expression levels of Lpin1, Dgat2, Apob, Lpl, Cpt-1, and Pparα were significantly increased (P < 0.05).ConclusionsThese results suggest that dietary emulsifier can enhance the fat utilization efficiency of broilers by increasing the small intestinal fatty acid uptake capacity, inhibiting hepatic fatty acid synthesis and promoting hepatic TG synthesis and transport capacity. This study provides valuable insights for the potential use of emulsifier supplementation to improve the performance of broiler chickens.

Loss of NAT10 alleviates maternal high-fat diet-induced hepatic steatosis in male offspring of mice.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is becoming an escalating health problem in pediatric populations. This study aimed to investigate the role of N-acetyltransferase 10 (NAT10) in maternal high-fat diet (HFD)-induced MASLD in offspring at early life. We generated male hepatocyte-specific NAT10 knockout (Nat10HKO) mice and mated them with female Nat10fl/fl mice under chow or HFD feeding. Body weight, liver histopathology, and expression of lipid metabolism-associated genes (Srebp1c, Fasn, Pparα, Cd36, Fatp2, Mttp, and Apob) were assessed in male offspring at weaning. Lipid uptake assays were performed both in vivo and in vitro. The mRNA stability assessment and RNA immunoprecipitation were performed to determine NAT10-regulated target genes. NAT10 deletion in hepatocytes of male offspring alleviated perinatal lipid accumulation induced by maternal HFD, decreasing expression levels of Srebp1c, Fasn, Cd36, Fatp2, Mttp, and Apob while enhancing Pparα expression. Furthermore, Nat10HKO male mice exhibited reduced lipid uptake. In vitro, NAT10 promoted lipid uptake by enhancing the mRNA stability of CD36 and FATP2. RNA immunoprecipitation assays exhibited direct interactions between NAT10 and CD36/FATP2 mRNA. NAT10 deletion in offspring hepatocytes ameliorates maternal HFD-induced hepatic steatosis through decreasing mRNA stability of CD36 and FATP2, highlighting NAT10 as a potential therapeutic target for pediatric MASLD.

#2903 Comprehensive lipidomic analysis reveals further insights into the molecular mechanism of podocyte lipotoxicity in Alport syndrome

Abstract Background and Aims The accumulation of lipids in podocytes has been shown to be a mediator of kidney injury in diabetic kidney disease (DKD). Recent animal studies have shown evidence of podocyte lipotoxicity in Alport syndrome (AS). First, discoidin domain receptor 1 (DDR1) is overactivated by excessive accumulation of α1 chain type 1 collagen in AS resulting in CD36 activation, producing direct podocyte injury by increasing reuptake of free fatty acids (FFAs). Furthermore, local overexpression of glomerular tumor necrosis factor has been observed in AS, which produces suppression of ABCA1, which affects mitochondrial function and decreases cholesterol efflux from podocytes, causing an accumulation of cholesterol and podocyte lipotoxicity. This study aimed to compare serum and urine lipidome variation between patients with AS and patients with DKD compared to healthy controls to explore the underlying molecular mechanisms of podocyte lipotoxicity in AS. Method A total of 63 samples from AS patients (COL4A3/4, n = 50, COL4A5, n = 13) were employed for this study, and compared to 15 samples from DKD patients and 20 samples from healthy volunteers considered as controls. We performed an untargeted lipidomics analysis to cover the broader spectrum of plasma and urine lipidome. Samples were analyzed by using an Agilent 1290 Infinity II Ultra-High-Performance Liquid-Chromatography system coupled to an Agilent 6546 Quadrupole Time-of-Flight Mass Spectrometer equipped with dual Agilent Jet Stream Electrospray ion source. For plasma samples, raw data matrix underwent normalization for sequence intensity correction based on the QC samples by using the support vector regression. For urine samples, normalization was performed using the Probabilistic Quotient Normalization to account for unwanted variance due to sample preparation and the analytical run. Results We generated a heatmap employing hierarchical clustering to visually represent the distinctions in statistically significant lipids across AS COL4A3/4, AS COL4A5, and DKD groups compared to the healthy control group, categorized by classes. Figure 1 summarizes the results of our study. In urine samples, a distinct decrease in acylcarnitines is evident in AS COL4A3/4 and AS COL4A5. Regarding the fatty acid (FA) lipid class, there is an increased general trend. FA 20:3 shows a meaningful increase in AS COL4A3/4 and DKD compared to the healthy control group, whereas in AS COL4A5, the trend of this lipid species is to decline when compared with COL4A3/4 and DKD levels. Concerning plasma samples, different trends were observed in AS COL4A3/4 and DKD depending on specific lipid species, while general reduced levels were reported in AS COL4A5. The phosphatidylcholine (PC) lipid species, implicated in various biological functions, display a drastic increase in the DKD urine group compared to the healthy control. The same trend is followed by AS COL4A3/4 and AS COL4A5 urine groups, with relatively similar data. Among the sphingolipids class, in urine, the overall trend of sphingomyelins (SM) for both AS COL4A3/4 and AS COL4A5 indicates a decrease in the levels of the statistically significant lipid species, with relatively similar levels between them. The neutral sphingolipids (HexCer) experience a general decrease in AS COL4A3/4, AS COL4A5 and DKD urine samples compared to the healthy control group. Lastly, the ceramides (Cer) follow a decreasing trend, where the most remarkable differences could be observed in the DKD urine group compared to the healthy controls. Conclusion Overall, the present study provided new insights into the mechanism of podocyte lipotoxicity in patients with AS. Increased specific plasma Cer and SM that are responsible for correct COL4A1 and COL4A2 formation might be responsible for aberrant COL1 expression DDR1 activation. Furthermore, specific essential FFAs that are involved in collagen synthesis are increased in AS, and might be indicating aberrant CD36 levels increasing their levels and enhancing their accumulation. Increased ABCA1 efflux activity is evident in higher extracellular levels of PC observed in urine samples from patients with AS.

Baoyuan decoction inhibits atherosclerosis progression through suppression peroxidized fatty acid and Src/MKK4/JNK pathway-mediated CD 36 expression

Background: Baoyuan decoction (BYD) has been widely utilized as a traditional prescription for the treatment of various conditions such as coronary heart disease, aplastic anemia, and chronic renal failure. However, its potential efficacy in improving atherosclerosis has not yet been investigated.Purpose: Our research aimed to assess the potential of BYD as an inhibitor of atherosclerosis and uncover the underlying mechanism by which it acts on foam cell formation.Study Design and Methods: High-fat diet-induced ApoE-/- mice were employed to explore the effect of BYD on atherosclerosis. The differential metabolites in feces were identified and analyzed by LC-Qtrap-MS. In addition, we utilized pharmacological inhibition of BYD on foam cell formation induced by oxLDL in THP-1 cells to elucidate the underlying mechanisms specifically in macrophages.Results: The atherosclerotic plaque burden in the aortic sinus of ApoE-/- mice was notably reduced with BYD treatment, despite no significant alterations in plasma lipids. Metabolomic analysis revealed that BYD suppressed the increased levels of peroxidized fatty acids, specifically 9/13-hydroxyoctadecadienoic acid (9/13-HODE), in the feces of mice. As a prominent peroxidized fatty acid found in oxLDL, we confirmed that 9/13-HODE induced the overexpression of CD36 in THP-1 macrophages by upregulating PPARγ. In subsequent experiments, the decreased levels of CD36 triggered by oxLDL were observed after BYD treatment. This decrease occurred through the regulation of the Src/MMK4/JNK pathway, resulting in the suppression of lipid deposition in THP-1 macrophages.Conclusions: These results illustrate that BYD exhibits potential anti-atherosclerotic effects by inhibiting CD36 expression to prevent foam cell formation.

Effects of oleogels (alpha-linolenic acid plus beeswax) extracted supplementation for approaching the therapeutic food ingredient: in vitro model

The dietary fatty acid intake for vascular disease has been highlighted for a decade. This study aimed to determine the effect of palmitic acid and fatty acid-incorporated beeswax (oleogels: OG) supplementation on anti-atherosclerotic effects through vascular smooth muscle cell (VSMC) activity. The A7r5 cells were cultured, cells were treated with three treatments, including 1) control, 2) palmitic acid (PA), and 3) alpha-linolenic acid (ALA) + beeswax, ratio 1:1 (OG) at different concentrations of 0, 25, 50 and 100 μM for 48 hrs. Cell proliferation, cell apoptosis, wound repair, and relative quantity of mRNA level of inflammatory cytokines and angiogenetic transcription factors were determined. The results showed there was a significantly reduced VSMCs proliferation with concentrationdependent (p &lt; 0.05). In the presence of OG at 100 μM, the wound area had healed after 24 hrs (59.2%) compared to PA (28.0%) group treatments. OG and PA supplementation significantly up-regulated eNOS and VEGF but down-regulated the TNF-α, CRP, CD36, iNOS, and NF-κB mRNA expression levels, while PA was a contrasting pattern (p &lt; 0.05). Therefore, supplementation of OG reduced the pro-inflammatory effects of inflammatory cytokines in macrophages and induced VEGF expression in VSMCs, contributing to anti-atherosclerotic effect.

The role and mechanism of the zinc finger gene ZNF580 in foam cell formation

Coronary atherosclerotic heart disease is an important threat to human health. The pathological basis is atherosclerosis, and foam cell formation is the key link in the initiation of atherosclerosis. Here, foam cell models were established using 50 ng/ml oxidized low-density lipoprotein (ox-LDL) to stimulate in vitro cultures of THP-1 cells for 72 h. The expression of ZNF580, a Cys2–His2 (C2H2) zinc finger protein containing 172 amino acids that was originally cloned by screening a human aortic cDNA library, was measured in foam cells, and its interaction with various regulatory factors during foam cell formation was investigated. Oil red O (ORO) staining was used to observe cell morphology and intracellular lipid levels. Lentivirus transfection was used to induce high ZNF580 expression (Ad-ZNF580) and low ZNF580 expression (Si-ZNF580) in THP-1 cells, and a fluorescent inverted microscope was used to observe the distribution of ZNF580 immunofluorescence to deduce the transfection rate. RNA and total protein were extracted, and the expression levels of ZNF580, cluster of differentiation 36 (CD36), peroxisome proliferator activated receptor-γ (PPAR-γ), ATP-binding cassette transporter A1 (ABCA1) and apolipoprotein E (ApoE) were measured by real-time quantitative PCR. The protein levels were examined by western blotting to evaluate the interaction between ZNF580 and associated regulatory factors. ZNF580 can significantly increase the expression levels of ApoE and ABCA1 and significantly decrease the expression levels of CD36 and PPAR-γ, suggesting that ZNF580-mediated inhibition of foam cell formation is associated with the PPAR-γ-CD36 signalling pathway. Based on these findings, ZNF580 might be a potential therapeutic candidate for the treatment of coronary atherosclerotic heart disease. Zhangzhongbai: ZNF580 inhibit foam cell formation