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Walnut oil as a dietary intervention for atherosclerosis: Efficacy and mechanistic pathways
IF 3.9 2区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-03-08 DOI: 10.1016/j.bbalip.2025.159607
Shujuan Hu , Si Tang , Dang Liu , Ruohan Xia , Xianwang Wang

Background and aims

Walnut oil (WO) and peanut oil (PO) are common vegetable oils rich in unsaturated fatty acids, known to alleviate atherosclerosis (AS) and reduce the risk of cardiovascular diseases (CVD). WO contains a higher proportion of polyunsaturated fatty acids (PUFAs) compared to PO. This study aimed to explore the influence of WO on AS and elucidate its potential mechanisms, providing a theoretical basis for enhancing the application of WO in functional foods and pharmaceuticals.

Methods

AS was established in rats using a high-fat diet and vitamin D3 injections. Rats with AS were administered WO or PO via gavage at a dose of 1.2 g/kg for 4 weeks. Serum lipid levels and arterial injury were assessed, and transcriptomic and metabolomic analyses of the rat vasculature were performed.

Results

Both WO and PO significantly lowered serum lipid levels and the atherogenic index (AI) in rats, reducing arterial wall injury and plaque formation. WO exhibited a more pronounced effect, particularly in decreasing serum levels of TG, TC, HDLC, and LDL-C. Transcriptomic analysis indicated that fatty acid, amino acid metabolism were crucial in AS development due to a high-fat diet. Metabolomic analysis indicated significant changes in the metabolism of arginine, proline, cysteine, methionine, glycine, serine and threonine in rats treated with WO.

Conclusion

WO and PO help alleviate AS by regulating lipid metabolism and influencing pivotal metabolic pathways like TCA cycle and cysteine-methionine metabolism. The more significant impact of WO indicates its potential as a dietary supplement for preventing and treating AS.
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引用次数: 0
Curcumin inhibits pancreatic steatosis in mice with a high-fat diet through the YAP/p53 pathway and confirmed through ultrasonic imaging
IF 3.9 2区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-02-21 DOI: 10.1016/j.bbalip.2025.159605
Helin Ke , Ziwei Xu , Lina Han , Han Wang , Guorong Lyu , Shilin Li

Aims

To investigate the mechanism by which curcumin inhibits pancreatic steatosis (PS), and the diagnostic value of ultrasonography in the pancreas of mice with obesity.

Materials and methods

Male mice were randomly divided into normal chow diet (NC), high-fat diet (HFD), and HFD + 80 mg/kg curcumin groups (HC) and maintained for 12 weeks to induce PS. Weight and fasting blood glucose (FBG) were collected biweekly and oral glucose tolerance test and insulin levels were measured in the final week. The morphology and fat infiltration of pancreas were observed by ultrasonography and histology. The level of blood lipid was detected, and the expression of genes and proteins related to lipid metabolism in pancreatic tissues was analyzed.

Results

Compared to the NC and HC groups, the HFD group had higher body weight, cholesterol, triglycerides, and LDL and HDL levels, along with increased inflammation and fat deposits in the pancreas. The HC group had milder inflammation and lower glucose intolerance and insulin resistance (P<0.05). The gray value, steatosis scores, immunohistochemical results, and ORO staining were significantly correlated (P<0.05). Correlations were found between gray values, steatosis scores, and ORO staining (P<0.05). In comparison to the HFD, expression of LATS2, FAS, YAP, and SREBP2 were downregulated and p53 was upregulated in the HC group.

Conclusion

Curcumin is a potential modulator of insulin resistance and SREBP2 expression, with its underlying mechanism possibly mediated through the YAP/p53 signaling pathway. Pancreatic steatosis exhibits distinct ultrasonographic features, making ultrasound an effective diagnostic tool for identifying the condition.
{"title":"Curcumin inhibits pancreatic steatosis in mice with a high-fat diet through the YAP/p53 pathway and confirmed through ultrasonic imaging","authors":"Helin Ke ,&nbsp;Ziwei Xu ,&nbsp;Lina Han ,&nbsp;Han Wang ,&nbsp;Guorong Lyu ,&nbsp;Shilin Li","doi":"10.1016/j.bbalip.2025.159605","DOIUrl":"10.1016/j.bbalip.2025.159605","url":null,"abstract":"<div><h3>Aims</h3><div>To investigate the mechanism by which curcumin inhibits pancreatic steatosis (PS), and the diagnostic value of ultrasonography in the pancreas of mice with obesity.</div></div><div><h3>Materials and methods</h3><div>Male mice were randomly divided into normal chow diet (NC), high-fat diet (HFD), and HFD + 80 mg/kg curcumin groups (HC) and maintained for 12 weeks to induce PS. Weight and fasting blood glucose (FBG) were collected biweekly and oral glucose tolerance test and insulin levels were measured in the final week. The morphology and fat infiltration of pancreas were observed by ultrasonography and histology. The level of blood lipid was detected, and the expression of genes and proteins related to lipid metabolism in pancreatic tissues was analyzed.</div></div><div><h3>Results</h3><div>Compared to the NC and HC groups, the HFD group had higher body weight, cholesterol, triglycerides, and LDL and HDL levels, along with increased inflammation and fat deposits in the pancreas. The HC group had milder inflammation and lower glucose intolerance and insulin resistance (<em>P</em>&lt;0.05). The gray value, steatosis scores, immunohistochemical results, and ORO staining were significantly correlated (<em>P</em>&lt;0.05). Correlations were found between gray values, steatosis scores, and ORO staining (<em>P</em>&lt;0.05). In comparison to the HFD, expression of LATS2, FAS, YAP, and SREBP2 were downregulated and p53 was upregulated in the HC group.</div></div><div><h3>Conclusion</h3><div>Curcumin is a potential modulator of insulin resistance and SREBP2 expression, with its underlying mechanism possibly mediated through the YAP/p53 signaling pathway. Pancreatic steatosis exhibits distinct ultrasonographic features, making ultrasound an effective diagnostic tool for identifying the condition.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 3","pages":"Article 159605"},"PeriodicalIF":3.9,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Preventive effect of siphonaxanthin, a carotenoid from green algae, against diabetic nephropathy and lipid metabolism insufficiency in skeletal muscle
IF 3.9 2区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-02-20 DOI: 10.1016/j.bbalip.2025.159604
Jiawen Zheng, Yuki Manabe, Tatsuya Sugawara
Diabetic nephropathy is a complication of diabetes mellitus characterized by the gradual progression of renal insufficiency, resulting in renal failure. Approximately 15 % or more of patients with type 2 diabetes mellitus have diabetic nephropathy. Siphonaxanthin is a green algal carotenoid noted for its strong biological activities, including anti-obesity effects. In this study, we aimed to evaluate the preventive effects of siphonaxanthin on diabetic nephropathy using db/db mice as a type 2 diabetes mellitus and diabetic nephropathy model. Ingestion of AIN-93G containing 0.004 % w/w siphonaxanthin did not improve plasma creatinine and urine albumin levels but significantly mitigated renal morphological changes in diabetic mice. Moreover, siphonaxanthin restored the decreased mRNA expression of fatty acid β-oxidation-related proteins in the skeletal muscle. These results indicate that siphonaxanthin can potentially ameliorate type 2 diabetes mellitus-induced kidney damage and lipid metabolism insufficiency in skeletal muscle. This study provides a possible daily nutraceutical solution for treating diabetic nephropathy and lipid metabolic abnormalities.
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引用次数: 0
Production, characterization and biodistribution of therapeutic high-density lipoprotein-like nanoparticles reconstituted with or without histidine-tagged recombinant ApoA1
IF 3.9 2区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-02-20 DOI: 10.1016/j.bbalip.2025.159606
Sarah Rosanaly , Marie Laurine Apalama , Matthieu Bringart , Pierre Giraud , Benoit Allard , Bryan Veeren , Olivier Meilhac , Joël Couprie , Philippe Rondeau
High-density lipoproteins (HDLs) are known for their cardiovascular protection due to apolipoprotein A-1 (ApoA1), their primary protein. ApoA1 promotes cholesterol reverse transport and exhibits antioxidant and anti-inflammatory properties. Although increasing HDL levels has not consistently reduced cardiovascular mortality in clinical trials, reconstituted HDL (rHDL) nanoparticles containing ApoA1 show potential in treating acute inflammation, such as in ischemic stroke, sepsis, and even COVID-19. ApoA1 is commonly produced in bacteria due to its simplicity and potential therapeutic optimisation. Addition of a histidine tag to recombinant ApoA1 may improve purification, stability and therapeutic efficacy, although its functional impact remains a subject of debate. In this study, ApoA1 with a poly-histidine tag (His-rApoA1) was produced in a clear coli system for simplified purification, followed by an evaluation of the tag's effects on rHDL nanoparticle properties. rHDL and His-rHDL nanoparticles were prepared using the sodium cholate dialysis method, combining recombinant rApoA1 or His-rApoA1 with phosphatidylcholine at a 1:75 M ratio. Nuclear magnetic resonance confirmed that both forms of rApoA1 structurally resembled plasma ApoA1, whether lipid-free or in nanoparticle form. Dynamic light scattering and electron microscopy revealed nanoparticle sizes around 7 nm with native HDL-like morphology. Testing on endothelial cells (EA.hy926) showed rapid uptake of rHDL and His-rHDL while preserving cell viability. Additionally, both nanoparticles reduced interleukin-6 and ICAM-1 expression in cells, demonstrating their anti-inflammatory and protective effects, unaffected by the poly-histidine tag. Intravenous injection in mice shows homogeneous distribution of His-rHDL in the liver, lungs, and spleen, with no cytotoxicity, indicating potential use for treating inflammatory diseases.
{"title":"Production, characterization and biodistribution of therapeutic high-density lipoprotein-like nanoparticles reconstituted with or without histidine-tagged recombinant ApoA1","authors":"Sarah Rosanaly ,&nbsp;Marie Laurine Apalama ,&nbsp;Matthieu Bringart ,&nbsp;Pierre Giraud ,&nbsp;Benoit Allard ,&nbsp;Bryan Veeren ,&nbsp;Olivier Meilhac ,&nbsp;Joël Couprie ,&nbsp;Philippe Rondeau","doi":"10.1016/j.bbalip.2025.159606","DOIUrl":"10.1016/j.bbalip.2025.159606","url":null,"abstract":"<div><div>High-density lipoproteins (HDLs) are known for their cardiovascular protection due to apolipoprotein A-1 (ApoA1), their primary protein. ApoA1 promotes cholesterol reverse transport and exhibits antioxidant and anti-inflammatory properties. Although increasing HDL levels has not consistently reduced cardiovascular mortality in clinical trials, reconstituted HDL (rHDL) nanoparticles containing ApoA1 show potential in treating acute inflammation, such as in ischemic stroke, sepsis, and even COVID-19. ApoA1 is commonly produced in bacteria due to its simplicity and potential therapeutic optimisation. Addition of a histidine tag to recombinant ApoA1 may improve purification, stability and therapeutic efficacy, although its functional impact remains a subject of debate. In this study, ApoA1 with a poly-histidine tag (His-rApoA1) was produced in a <em>clear coli</em> system for simplified purification, followed by an evaluation of the tag's effects on rHDL nanoparticle properties. rHDL and His-rHDL nanoparticles were prepared using the sodium cholate dialysis method, combining recombinant rApoA1 or His-rApoA1 with phosphatidylcholine at a 1:75 M ratio. Nuclear magnetic resonance confirmed that both forms of rApoA1 structurally resembled plasma ApoA1, whether lipid-free or in nanoparticle form. Dynamic light scattering and electron microscopy revealed nanoparticle sizes around 7 nm with native HDL-like morphology. Testing on endothelial cells (EA.hy926) showed rapid uptake of rHDL and His-rHDL while preserving cell viability. Additionally, both nanoparticles reduced interleukin-6 and ICAM-1 expression in cells, demonstrating their anti-inflammatory and protective effects, unaffected by the poly-histidine tag. Intravenous injection in mice shows homogeneous distribution of His-rHDL in the liver, lungs, and spleen, with no cytotoxicity, indicating potential use for treating inflammatory diseases.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 3","pages":"Article 159606"},"PeriodicalIF":3.9,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Unveiling BCO2 function in macular pigment metabolism: Mitochondrial processing and expression in the primate retina
IF 3.9 2区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-02-18 DOI: 10.1016/j.bbalip.2025.159600
Chou Shen, Sepalika Bandara, Sanae S. Imanishi, Mahip Kalra, Yoshikazu Imanishi, Johannes von Lintig
BCO2 (β-carotene oxygenase 2) converts carotenoids into apocarotenoids by oxidative cleavage across double bonds and controls carotenoid homeostasis in vertebrate tissues. In this study, we examined BCO2's expression, localization, and activity in human cell lines and the retina. We generated peptide antibodies directed against primate BCO2 and validated their specificity using recombinant BCO1 (β-carotene oxygenase 1) and BCO2 proteins expressed in bacteria. The antibodies specifically detected human BCO2 by Western blot. In BCO2 expressing HepG2 cells, the antibodies recognized a 65 kDa mitochondrial protein that co-migrated with a recombinant truncated 522-amino-acid BCO2 variant, suggesting post-translational processing of the 579 amino acid long human BCO2 protein. Immunohistochemical analysis of macaque retina sections revealed BCO2 localization in the retinal pigment epithelium, photoreceptor inner segments, plexiform layer, and ganglion cell layer. Co-staining with COX IV indicated a mitochondrial localization of retinal BCO2 within photoreceptor inner segments. Western blot analysis of human donor retinas, separated into central and peripheral regions, identified higher BCO2 expression in the peripheral retina. Enzymatic activity assays demonstrated that BCO2 interacted with Aster proteins that transport carotenoids within cells. Our studies establish BCO2 as a mitochondrial protein expressed in the primate retina, where it likely plays a pivotal role in the metabolism of macular pigments and the maintenance of retinal health.
{"title":"Unveiling BCO2 function in macular pigment metabolism: Mitochondrial processing and expression in the primate retina","authors":"Chou Shen,&nbsp;Sepalika Bandara,&nbsp;Sanae S. Imanishi,&nbsp;Mahip Kalra,&nbsp;Yoshikazu Imanishi,&nbsp;Johannes von Lintig","doi":"10.1016/j.bbalip.2025.159600","DOIUrl":"10.1016/j.bbalip.2025.159600","url":null,"abstract":"<div><div>BCO2 (β-carotene oxygenase 2) converts carotenoids into apocarotenoids by oxidative cleavage across double bonds and controls carotenoid homeostasis in vertebrate tissues. In this study, we examined BCO2's expression, localization, and activity in human cell lines and the retina. We generated peptide antibodies directed against primate BCO2 and validated their specificity using recombinant BCO1 (β-carotene oxygenase 1) and BCO2 proteins expressed in bacteria. The antibodies specifically detected human BCO2 by Western blot. In BCO2 expressing HepG2 cells, the antibodies recognized a 65 kDa mitochondrial protein that co-migrated with a recombinant truncated 522-amino-acid BCO2 variant, suggesting post-translational processing of the 579 amino acid long human BCO2 protein. Immunohistochemical analysis of macaque retina sections revealed BCO2 localization in the retinal pigment epithelium, photoreceptor inner segments, plexiform layer, and ganglion cell layer. Co-staining with COX IV indicated a mitochondrial localization of retinal BCO2 within photoreceptor inner segments. Western blot analysis of human donor retinas, separated into central and peripheral regions, identified higher BCO2 expression in the peripheral retina. Enzymatic activity assays demonstrated that BCO2 interacted with Aster proteins that transport carotenoids within cells. Our studies establish BCO2 as a mitochondrial protein expressed in the primate retina, where it likely plays a pivotal role in the metabolism of macular pigments and the maintenance of retinal health.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 3","pages":"Article 159600"},"PeriodicalIF":3.9,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143444350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Pain and functional limitations in knee osteoarthritis are reflected in the fatty acid composition of plasma extracellular vesicles
IF 3.9 2区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-02-17 DOI: 10.1016/j.bbalip.2025.159602
Anne-Mari Mustonen , Petro Julkunen , Laura Säisänen , Lauri Karttunen , Amir Esrafilian , Jusa Reijonen , Sylvain Tollis , Reijo Käkelä , Sanna P. Sihvo , Nina Höglund , Tytti Niemelä , Anna Mykkänen , Jussi Mäki , Heikki Kröger , Jari Arokoski , Petteri Nieminen
This study investigated relationships between fatty acid (FA) profiles of extracellular vesicles (EVs) and cartilage degradation, functional limitations, pain, and psychological well-being in knee osteoarthritis (KOA). Fasting plasma was collected from controls (n = 10), end-stage KOA patients at baseline (n = 12) and at 3 and 12 months (n = 11 and 9) after joint replacement surgery, and from KOA synovial fluid (SF) at baseline (n = 10). EVs were isolated with the exoEasy Maxi Kit or size-exclusion chromatography, and EV FAs were analyzed with gas chromatography–mass spectrometry. Articular cartilage loss was determined by magnetic resonance imaging, and knee pain and function were assessed through questionnaires and physiatric and neuromuscular examinations. The associations of these data with EV FA proportions were tested with the univariate analysis of variance adjusted for age and body adiposity. Higher proportions of 16:1n-7, 18:1n-7, and total monounsaturated FAs in plasma EVs were associated with less severe KOA symptoms, while higher 24:1n-9, total saturated FAs, and ratios of arachidonic acid to long-chain n-3 polyunsaturated FAs (PUFAs) were linked to KOA pain, independent of age and body adiposity. In SF EVs, higher product/precursor ratios of n-6 PUFAs were associated with increased joint stiffness, and higher total dimethyl acetals were linked to physical disability. EV FAs emerged as significant indicators of knee pain and function. The results can be utilized to discover novel biomarkers for KOA and may have implications for targeted prevention and treatment of KOA symptoms by using EVs with a specific FA cargo.
{"title":"Pain and functional limitations in knee osteoarthritis are reflected in the fatty acid composition of plasma extracellular vesicles","authors":"Anne-Mari Mustonen ,&nbsp;Petro Julkunen ,&nbsp;Laura Säisänen ,&nbsp;Lauri Karttunen ,&nbsp;Amir Esrafilian ,&nbsp;Jusa Reijonen ,&nbsp;Sylvain Tollis ,&nbsp;Reijo Käkelä ,&nbsp;Sanna P. Sihvo ,&nbsp;Nina Höglund ,&nbsp;Tytti Niemelä ,&nbsp;Anna Mykkänen ,&nbsp;Jussi Mäki ,&nbsp;Heikki Kröger ,&nbsp;Jari Arokoski ,&nbsp;Petteri Nieminen","doi":"10.1016/j.bbalip.2025.159602","DOIUrl":"10.1016/j.bbalip.2025.159602","url":null,"abstract":"<div><div>This study investigated relationships between fatty acid (FA) profiles of extracellular vesicles (EVs) and cartilage degradation, functional limitations, pain, and psychological well-being in knee osteoarthritis (KOA). Fasting plasma was collected from controls (<em>n</em> = 10), end-stage KOA patients at baseline (<em>n</em> = 12) and at 3 and 12 months (<em>n</em> = 11 and 9) after joint replacement surgery, and from KOA synovial fluid (SF) at baseline (<em>n</em> = 10). EVs were isolated with the exoEasy Maxi Kit or size-exclusion chromatography, and EV FAs were analyzed with gas chromatography–mass spectrometry. Articular cartilage loss was determined by magnetic resonance imaging, and knee pain and function were assessed through questionnaires and physiatric and neuromuscular examinations. The associations of these data with EV FA proportions were tested with the univariate analysis of variance adjusted for age and body adiposity. Higher proportions of 16:1n-7, 18:1n-7, and total monounsaturated FAs in plasma EVs were associated with less severe KOA symptoms, while higher 24:1n-9, total saturated FAs, and ratios of arachidonic acid to long-chain n-3 polyunsaturated FAs (PUFAs) were linked to KOA pain, independent of age and body adiposity. In SF EVs, higher product/precursor ratios of n-6 PUFAs were associated with increased joint stiffness, and higher total dimethyl acetals were linked to physical disability. EV FAs emerged as significant indicators of knee pain and function. The results can be utilized to discover novel biomarkers for KOA and may have implications for targeted prevention and treatment of KOA symptoms by using EVs with a specific FA cargo.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 3","pages":"Article 159602"},"PeriodicalIF":3.9,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143456787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The influence of IMPDH activity on ciliogenesis and adipogenesis of 3T3-L1 cells while undergoing differentiation
IF 3.9 2区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-02-15 DOI: 10.1016/j.bbalip.2025.159603
Kolsoom Shahdadnejad, Razieh Yazdanparast
The functional roles of primary cilia and inosine 5′-monophosphate dehydrogenase (IMPDH) are among the hot topics in today's adipogenesis research. Considering the reported interaction between IMPDH and ADP Ribosylation Factor-Like GTPase 13B (ARL13B), as a key ciliary protein, our study focused on this interaction during the ciliogenesis process while 3T3-L1 pre-adipocytes undergoing differentiation to lipid-accumulating adipocytes. Our results indicated that, in the early days of differentiation, when cilium length is long, IMPDH expression is high and its interaction with ARL13B is low. Conversely, in the last days of differentiation, the cilia length and IMPDH expression reduced while, the IMPDH/ARL13B interaction remains high relative to the initial days. In either of these two situations, IMPDH was not documented within the cilia. The extent of the interaction between IMPDH and ARL13B might account for the lack of co-localization of IMPDH and ARL13B within cilia during the process of differentiation. Although, inhibiting IMPDH in the early days of differentiation did not have a significant effect on cilia length, it did reduce adipogenesis by limiting mitotic clonal expansion through arresting cells in the G1/G0 phase. These findings provide the ground for further research to investigate the relationship between the IMPDH/ARL13B interaction and cilia length, which decline in obesity.
{"title":"The influence of IMPDH activity on ciliogenesis and adipogenesis of 3T3-L1 cells while undergoing differentiation","authors":"Kolsoom Shahdadnejad,&nbsp;Razieh Yazdanparast","doi":"10.1016/j.bbalip.2025.159603","DOIUrl":"10.1016/j.bbalip.2025.159603","url":null,"abstract":"<div><div>The functional roles of primary cilia and inosine 5′-monophosphate dehydrogenase (IMPDH) are among the hot topics in today's adipogenesis research. Considering the reported interaction between IMPDH and ADP Ribosylation Factor-Like GTPase 13B (ARL13B), as a key ciliary protein, our study focused on this interaction during the ciliogenesis process while 3T3-L1 pre-adipocytes undergoing differentiation to lipid-accumulating adipocytes. Our results indicated that, in the early days of differentiation, when cilium length is long, IMPDH expression is high and its interaction with ARL13B is low. Conversely, in the last days of differentiation, the cilia length and IMPDH expression reduced while, the IMPDH/ARL13B interaction remains high relative to the initial days. In either of these two situations, IMPDH was not documented within the cilia. The extent of the interaction between IMPDH and ARL13B might account for the lack of co-localization of IMPDH and ARL13B within cilia during the process of differentiation. Although, inhibiting IMPDH in the early days of differentiation did not have a significant effect on cilia length, it did reduce adipogenesis by limiting mitotic clonal expansion through arresting cells in the G1/G0 phase. These findings provide the ground for further research to investigate the relationship between the IMPDH/ARL13B interaction and cilia length, which decline in obesity.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 3","pages":"Article 159603"},"PeriodicalIF":3.9,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143439827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
What was the scientific context in which I wrote my 1975 “Inositol phospholipids and cell surface receptor function” review?
IF 3.9 2区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-02-12 DOI: 10.1016/j.bbalip.2025.159601
Robert H. (Bob) Michell
50 years on from my BBA review, I was delighted to hear that many of the current leaders of research across “The Multiverse of Phosphoinositides” are contributing to an authoritative collection of articles on the current state of that cosmology of cell functions – and that three other inositidonauts who were launched from Birmingham are assembling it. When the phosphoinositidase C signalling pathway emerged into the cell regulation limelight during the early 1980s it drew attention to a family of metabolically atypical membrane phospholipids that most biologists had been comfortably ignoring. Looking back, it is remarkable how many important clues were already loitering in the literature, waiting for us to start to make sense of them in the 1970s.
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引用次数: 0
RGFP966 inhibits palmitic acid induced VSMCs phenotypic transition by targeting ATGL
IF 3.9 2区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-01-28 DOI: 10.1016/j.bbalip.2025.159597
Siyi Zhang , Fangqin Nie , Youjie Zeng , Zhousheng Yang , Wenmin Song , Xin Yan , Zizhao Tang , Yangxia Fu , Ren Guo

Background

The phenotypic switch of vascular smooth muscle cells (VSMCs) underlies the pathology of many cardiovascular diseases. Histone deacetylase 3 (HDAC3) is reported to upregulate in several cardiovascular diseases. RGFP966 is a highly selective HDAC3 inhibitor. This study aimed to explore the effects of RGFP966 on the phenotypic switch of VSMCs.

Method

First, we conducted an analysis of HDAC3 expression utilizing pertinent Gene Expression Omnibus (GEO) datasets. Then CCK-8, Edu, and wound healing assays were used to explore the effects of RGFP966 on the proliferation and migration of VSMCs and potential mechanisms at the cellular level.

Results

Our results showed that palmitic acid (PA) induced the accumulation of lipid droplets in VSMCs, downregulated Adipose triglyceride lipase (ATGL), and increased VSMC viability and migration, which were significantly reversed by RGFP966. Additionally, siRNA targeting ATGL dramatically enhanced the VSMCs injury induced by PA. The autophagy inhibitor 3-Methyladenine (3-MA) partially reversed the decreased ATGL expression caused by PA. Furthermore, the p-mTOR/mTOR ratio decreased under PA induction and rebounded after administration of RGFP966.

Conclusion

RGFP966 has a protective effect against VSMCs phenotype transitions, potentially related to the regulation of ATGL.
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引用次数: 0
Decoding the excited-state dynamics of carbonyl-containing carotenoids: Insights from the Ind series
IF 3.9 2区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-01-28 DOI: 10.1016/j.bbalip.2025.159598
Daisuke Kosumi , Toshiyuki Kusumoto , Hideki Hashimoto
Carotenoids are naturally occurring pigments essential for both light-harvesting and photoprotection in photosynthetic processes. Among these, carbonyl-containing carotenoids exhibit distinctive excited state properties due to the presence of intramolecular charge transfer (ICT) in their excited states. In this study, we synthesized a novel family of carotenoid analogs with varying numbers of conjugated double bonds, denoted as the Ind series, and conducted femtosecond pump-probe spectroscopy on these molecules in both acetone and n-hexane. The objective was to elucidate how the excited-state dynamics depend on the conjugation length. The spectroscopic characterization of the Ind series revealed several unique features: the observation of stimulated emission from the 1Ag/ICT state, the emergence of the 1nπ state, triplet state formation mediated by the 1nπ state, and an anomalous solvent dependence of the 1Ag/ICT state lifetimes. The relationship between conjugation length and excited state dynamics, as well as the ICT character of the Ind series, are thoroughly discussed.
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引用次数: 0
期刊
Biochimica et biophysica acta. Molecular and cell biology of lipids
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