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PubMed1961

Further studies on seroreactivity in leprosy by means of a lecithin-free cardiolipin antigen (cardchol) and other antigens ordinarily used in the serodiagnosis of treponematoses.

In a previous study the reactivities of some lipoidal antigens in sera from patients with different types of leprosy were investigated. The present paper is a continuation of this earlier study and relates to an investigation of some 300 sera from leprosy patients in India. In particular, the reactivity of cardchol (a complement-fixing, lecithin-free, cardiolipin antigen) is compared with that of CWRM (an "ordinary" cardiolipin antigen used in routine complement-fixation tests for the serodiagnosis of treponematoses).Cardchol, which is inferior to CWRM in reactivity with treponemal sera, has proved to be more reactive than CWRM in leprosy sera. The use of a lecithin-free cardiolipin antigen in serological investigations has revealed that the antilipoidal antibodies occurring in leprosy are most probably different from those demonstrated in treponematoses. Among the sera of non-syphilitic lepers, the percentage reactivity was significantly higher with cardchol than with CWRM. Thus, by changing the relative proportions of the three components of cardiolipin antigen, it has been possible to produce antigens with reactivities quite different from those of the antigens ordinarily used for the serological demonstration of syphilis.Cardchol is by no means a specific antigen for the demonstration of leprosy, but it has the ability to fix antibodies in certain leprosy sera that are not fixed by the ordinary CWRM antigen.

Antibodies↗

PubMed1991

[Cardiolipin antibodies in non-specific aortic arteritis].

Cardiolipin antibodies are detected in the sera from patients having a wide range of clinical manifestations, including venous and arterial thrombosis, obstetric abnormality, damaged CHS and diseased vascular wall. To clarify the clinical value of cardiolipin antibodies, 21 patients with non-specific aortic arteritis were studied. The antibodies were determined by enzyme immunoassay. Their higher levels were found in 5 (24%) patients. The patients who were positive for cardiolipin antibodies showed a significant increase in the incidence of occlusive lesions (p less than 0.001) and a moderate increase in that of valvular heart diseases. The findings suggest that cardiolipin antibodies might contribute to the pathogenesis of non-specific of aortic arteritis.

Adolescent↗

PubMedDate not supplied

Quantitative profile of cardiolipin and group treponemal IgD antibodies in syphilis estimated by single radial immunodiffusion technique (SRID).

150 serum samples (reactive in VDRL, Reiter-ELISA, FTA-Abs tests), from male patients 25-45 years old, in various stages of syphilis whether treated or untreated, were tested for IgD by SRID. On 154 sera from healthy males 25-45 years old, the reference normal values for IgD levels were established, as: 0-131.2 IU/ml with a mean of 29.92 +/- 29.61 IU/ml. Cardiolipin and group treponemal fraction values for IgD class were obtained by assessing the difference between the immunodiffusion diameter values produced by sera before and after complete absorption with VDRL antigen or delipidated T. reiteri suspension. The individual, mean +/- SD values (expressed in IU/ml) and the percentage of cardiolipin and treponemal IgD of the total IgD class were calculated for each stage. The mean value of the total IgD class, excepting secondary syphilis (sigma 2) 52.53 +/- 26.66 IU/ml), did not overstep the normal levels but all minimal individual values from syphilitic patients (7.09-14.89 IU/ml) surpassed significantly the normal minimal values which were less than or equal to 3.54 IU/ml. The total lack of cardiolipin (IgD and the presence of group treponemal IgD in all sera of the syphilis stages studied were manifest. The group treponemal IgD mean values ranged between 7-9 IU/ml, with a maximum of 19.32 +/- 10.58 IU/ml in sigma 2 followed by latent syphilis (sigma lat) with a mean value of 9.37 +/- 4.9 IU/ml. A significant percentage of treponemal IgD vs total IgD was recorded: primary syphilis (sigma 1) 32.01%, primary-secondary syphilis (sigma 1-2) 28.76%, sigma 2 36.77%, sigma lat and treated persistent seroreactive syphilis (sigma t+) 29.61%. The high proportion of treponemal IgD in latent and treated persistent reactive syphilis suggests a steady activation of B lymphocytes by treponemal antigens and presumably is an expression of an active infectious process. The absence of cardiolipin IgD and the presence of only the treponemal IgD, in all sera from all stages, might confer to their detection an extremely specific diagnostic value in syphilis.

Adult↗

PubMed1986

Comparative pharmacokinetics of free doxorubicin and doxorubicin entrapped in cardiolipin liposomes.

The comparative pharmacokinetics of free doxorubicin and doxorubicin entrapped in cardiolipin liposomes was evaluated in rats at a dose of 6 mg/kg i.v. Doxorubicin was entrapped in cardiolipin liposomes by using 11.2 mumol of drug, 5.6 mumol of cardiolipin, 28.5 mumol of phosphatidylcholine, 19.5 mumol of cholesterol, and 11.1 mumol of stearylamine. The peak plasma concentration with free doxorubicin at 5 min was 1.7 micrograms/ml which was reduced to 0.3 micrograms/ml by 1 h. With cardiolipin liposomes, the peak plasma concentration of doxorubicin achieved at 5 min was 20.9 micrograms/ml. The plasma levels of doxorubicin decreased gradually and by 1 h the drug concentration in plasma was 10 micrograms/ml. The plasma levels of free doxorubicin and doxorubicin entrapped in liposomes were fitted to a 3-compartment computer model. The terminal half-life with free doxorubicin in plasma was 17.3 h whereas it was 69.3 h with drug entrapped in liposomes. The area under the plasma concentration curve with liposomal doxorubicin was 81.4 micrograms X h X ml-1 compared to 1.95 micrograms X h X ml-1 observed with free doxorubicin. The steady state volume of distribution with free doxorubicin was about 23-fold higher than liposomal doxorubicin. The terminal half-life with free doxorubicin in cardiac tissue was 17.9 h compared to 12.6 h with drug encapsulated in liposomes. The terminal half-lives in liver and spleen following administration of liposomal doxorubicin were 15- and 2.3-fold higher, respectively, compared to free drug; furthermore, the concentration X time values of liposomal doxorubicin in liver were 26-fold higher and in spleen 6-fold higher than the free drug. Free doxorubicin and doxorubicin entrapped in liposomes demonstrated 17 and 20% excretion in bile of the injected dose, respectively, in rats. The present studies demonstrate that liposomal encapsulation of doxorubicin significantly alters its pharmacokinetics in plasma and tissues compared to free drug.

Animals↗

PubMed1985

Isolation and purification of cardiolipin from beef heart.

A simple and efficient procedure is described for the preparation of cardiolipin sodium salt from beef heart. A crude phospholipid fraction is isolated by chloroform-methanol extraction of the homogenized tissue, followed by acetone precipitation and reprecipitation in 4% aqueous CaCl2-methanol. Cardiolipin is separated from the calcium salts of the acidic phospholipids by partition column chromatography on silica gel (Polygosil 60-63100) using 2-propanol-cyclohexane-water 50:43:7 (v/v/v) as eluent. Further purification of the cardiolipin is achieved by high performance liquid chromatography of the calcium salt on silica gel (Lichrosorb Si 60-5) with a neutral eluent (2-propanol-cyclohexane-water 45:50:5 (v/v/v], followed by quantitative conversion to the sodium salt. The yield of this procedure is 1.5-2.1 g of pure 99% sodium salt of cardiolipin per kg of moist ventricular tissue.

Animals↗

PubMed1981

Cardiolipin requirement for electron transfer in complex I and III of the mitochondrial respiratory chain.

Almost complete phospholipid depletion has been achieved for Complex I and III of the mitochondrial respiratory chain using a technique that involves elution on Sephadex LH-20 in the presence of Triton X-100. Enzymic activity may be regenerated by replenishment with phospholipid. However, restoration of enzymic activity in phospholipid-depleted Complex I and III has been shown to require the presence of cardiolipin. These results are, therefore, similar to findings on the absolute catalytic requirement of cardiolipin for cytochrome oxidase activity (Fry, M., and Green, D. E. (1980) Biochem. Biophys. Res. Commun. 93, 1238-1246). At least two roles for phospholipid involvement in electron transfer processes are proposed, a catalytic role provided specifically by cardiolipin and a dispersive role that may be provided by various phospholipids or detergents. The absolute requirement of enzymic activity for cardiolipin suggests that this phospholipid plays a crucial role in the coupled electron transfer process.

Animals↗

PubMed1998

Docosahexaenoic acid accumulates in cardiolipin and enhances HT-29 cell oxidant production.

The objective of this study was to investigate membrane fatty acids for their effects on mitochondrial function in live cells. Mitochondrial potential and oxidant production were measured in human colonic adenocarcinoma (HT-29) cells with membranes enhanced in either oleic acid, linoleic acid, arachidonic acid, eicosapentaenoic acid, or docosahexaenoic acid. Docosahexaenoic acid-enriched cells had increased mitochondrial potential and produced 5-fold more cellular oxidants than did cells enriched with any other fatty acid. Oxidant production in fatty acid-enriched HT-29 cells did not correlate with the degree of unsaturation for total membrane fatty acids. However, there was a strong correlation between the degree of fatty acid unsaturation of cardiolipin, a critical inner-mitochondrial membrane phospholipid, and oxidant production. Cardiolipin acyl composition is known to influence the activity of electron transport complexes, an effect that can increase mitochondrial oxidant production. Docosahexaenoic acid was enriched to 48 mol% of the fatty acids present in HT-29 cell cardiolipin. These results demonstrate the importance of membrane acyl composition to mitochondrial potential and oxidant production in live cells. Additionally, results suggest that docosahexaenoic acid increases cell oxidant production by accumulating in cardiolipin, where its presence alters electron transport efficiency.

Cardiolipins↗

PubMed1996

Increased levels of autoantibodies to cardiolipin and oxidised low density lipoprotein are inversely associated with plasma vitamin C status in cigarette smokers.

In this study we have measured circulating levels of autoantibodies to cardiolipin and oxidised low-density lipoprotein (ox-LDL) and correlated these with plasma concentrations of the anti-oxidant nutrients vitamin C, vitamin E and beta-carotene, in a group (79) of asymptomatic, male cigarette smokers and in non-smoking control subjects. Cigarette smoking, a well-known risk factor for development of atherosclerosis, was found to be associated with moderately elevated levels of autoantibodies to both cardiolipin and ox-LDL. Increased levels of these autoantibodies were most evident in the older smokers (> 30 years) and were significantly and inversely correlated with plasma vitamin C, but not with vitamin E or beta-carotene. Absorption studies designed to investigate the specificity of these autoantibodies demonstrated a high degree of cross-reactivity of cardiolipin antibodies with ox-LDL, while antibodies to the oxidatively modified lipoprotein tended to be specific for this antigen. These findings suggest that cigarette smoking promotes formation of autoantibodies to both cardiolipin and ox-LDL and that these may be involved in the initiation and/or perpetuation of atherosclerosis. Dietary intake of vitamin C may be a determinant of susceptibility to development of this cardiovascular disorder.

Adult↗

PubMed1998

YDL142c encodes cardiolipin synthase (Cls1p) and is non-essential for aerobic growth of Saccharomyces cerevisiae.

The unassigned open reading frame YDL142c was identified to code for cardiolipin synthase, Cls1p. A cls1 deletion strain is viable on glucose, galactose, ethanol, glycerol and lactate containing media, although the growth rate on non-fermentable carbon sources is decreased. Mitochondria of the cls1 mutant are devoid of cardiolipin but accumulate the cardiolipin precursor phosphatidylglycerol when grown on non-fermentable carbon sources. Specific activity of phosphatidylglycerolphosphate synthase in cls1 is reduced to 30-75% of the wild-type level. Amounts of mitochondrial cytochromes and activity of cytochrome c oxidase, however, are not affected in the cls1 deletion strain. Collectively, these data indicate that cardiolipin is not essential for aerobic growth of Saccharomyces cerevisiae.

Anaerobiosis↗

PubMed2003

Anti-cardiolipin/beta-2 glycoprotein activities co-exist on human anti-DNA antibody light chains.

We have recently shown that the human anti-DNA antibodies B3 and 33H11 also bind cardiolipin and that the anti-autoantigen activity resides predominantly on their lambda light chains. We now show that the two auto-antibodies possess strong reactivity to the plasma-protein 2-Glycoprotein I (beta2-GPI) also. Utilizing chain shuffling experiments involving an unrelated anti-p185 antibody 4D5 with insignificant reactivity to cardiolipin or to beta2-GPI, we now demonstrate that hybrid Fabs with constituent light chain, but not the heavy chain, of B3 or 33H11, exhibit anti-cardiolipin activity. Furthermore, the constructs possessing the auto-antibody-derived light chain also exhibited significant reactivity to beta2-GPI. The results suggest that anti-DNA, anti-cardiolipin and anti-beta2-GPI activities co-exist on the light chains of the antibodies studied and, importantly, these activities could be transferred to antibody constructs by their light chains alone. Computer-generated models of the three-dimensional structures of the auto-antibodies and their hybrids, suggest predominant interaction of their light chains with domain IV of beta2-GPI.

Amino Acid Sequence↗

PubMed2003

Saturated fatty acid-induced apoptosis in MDA-MB-231 breast cancer cells. A role for cardiolipin.

Little is known about the biochemical basis of the action of free fatty acids (FFA) on breast cancer cell proliferation and apoptosis. Here we report that unsaturated FFAs stimulated the proliferation of human MDA-MB-231 breast cancer cells, whereas saturated FFAs inhibited it and caused apoptosis. Saturated FFA palmitate decreased the mitochondrial membrane potential and caused cytochrome c release. Palmitate-induced apoptosis was enhanced by the fat oxidation inhibitor etomoxir, whereas it was reduced by fatty-acyl CoA synthase inhibitor triacsin C. The non-metabolizable analog 2-bromopalmitate was not cytotoxic. This indicates that palmitate must be metabolized to exert its toxic effect but that its action does not involve fat oxidation. Pharmacological studies showed that the action of palmitate is not mediated via ceramides, reactive oxygen species, or changes in phosphatidylinositol 3-kinase activity. Palmitate caused early enhancement of cardiolipin turnover and decreased the levels of this mitochondrial phospholipid, which is necessary for cytochrome c retention. Cosupplementation of oleate, or increasing beta-oxidation with the AMP-activated protein kinase activator, 5-aminoimidazole-4-carboxamide-1-beta-D-ribonucleoside, both restored cardiolipin levels and blocked palmitate-induced apoptosis. Oleate was preferentially metabolized to triglycerides, and oleate cosupplementation channeled palmitate esterification processes to triglycerides. Overexpression of Bcl-2 family members blocked palmitate-induced apoptosis. The results provide evidence that a decrease in cardiolipin levels and altered mitochondrial function are involved in palmitate-induced breast cancer cell death. They also suggest that the antiapoptotic action of oleate on palmitate-induced cell death involves both restoration of cardiolipin levels and redirection of palmitate esterification processes to triglycerides.

Apoptosis↗

PubMed1991

Amplification and substantial purification of cardiolipin synthase of Escherichia coli.

A simple, specific, and sensitive assay procedure for cardiolipin synthase of Escherichia coli has been developed. This measures the radioactivity of glycerol formed from phosphatidyl [2-3H]glycerol and is mainly based on the findings that 400 mM phosphate and 0.015% Triton X-100 markedly activate the enzyme. Cardiolipin synthase was amplified 760-fold upon induction with isopropyl beta-D-thiogalactoside in cells harboring a pBR322 derivative in which the cls gene encoding this enzyme was preceded by the tac promoter. Under these conditions, cardiolipin content increased, membrane potential decreased, spheroplasts became fragile, cells lost viability, and inducer-resistant mutants appeared at a high frequency. The amplification enabled the isolation of an enzyme preparation with a specific activity approximately 10,000-times higher than that of wild-type whole cell lysate. This purification was simply achieved by extraction of the crude membrane fraction with Triton X-100 and a single phosphocellulose column chromatography. This preparation, together with the crude envelope fraction, was used to characterize the basic properties of E. coli cardiolipin synthase, some of which were utilized in setting up the assay conditions.

Detergents↗

PubMed2003

Cross-reactivity between anti-cardiolipin, anti-high-density lipoprotein and anti-apolipoprotein A-I IgG antibodies in patients with systemic lupus erythematosus and primary antiphospholipid syndrome.

OBJECTIVES: Atherosclerosis is an important complication of patients with systemic lupus erythematosus (SLE) and primary antiphospholipid syndrome (APS). One suggested mechanism may be the action of autoantibodies directed against plasma lipoproteins. We studied the presence and patterns of cross-reactivity between antibodies directed against cardiolipin, high-density lipoprotein (HDL) and apolipoprotein A-I (Apo A-I) in patients with SLE and APS. METHODS: Sera from 50 patients (25 SLE and 25 APS) and 10 healthy controls together with three human immunoglobulin G anti-cardiolipin (CL) monoclonal antibodies (IS4, CL1 and CL24) were assessed for the presence of autoantibodies binding cardiolipin, HDL and Apo A-I. Classical inhibition assays were performed to study interference by HDL and Apo A-I in the binding of the human monoclonal antibody to CL. To determine the cross-reactivity patterns between these autoantibodies, sera from 12 patients were incubated on ELISA plates coated with the three different molecules and the captured antibodies were then tested for their activity towards each of the other antigens. RESULTS: All three monoclonals bound to CL. IS4 and CL1 also bound to HDL but only IS4 bound to Apo A-I. Anti-cardiolipin titres were higher in patients with APS than SLE and in healthy controls (P<0.03 and P<0.009 respectively). Titres of antibodies to HDL were higher in patients with SLE and APS than in controls (P<0.009 and P<0.03 respectively). There were no significant differences with respect to the presence of antibodies binding to Apo A-I. In the SLE population, anti-HDL antibody titres correlated with anti-Apo A-I (r=0.563, P<0.004), but not in patients with APS. In the cross-reactive assay, 11/12 (91.7%) of the samples containing isolated anti-CL antibodies reacted to HDL and 2/12 (16.7%) to Apo A-I. Samples containing isolated anti-HDL antibodies also reacted with CL and Apo A-I (7/12 and 3/12 respectively). All samples collected after incubation with Apo A-I bound to HDL and 6/12 (50%) to CL. There were no differences in the cross-reactivity patterns between patients with SLE and APS. CONCLUSIONS: Patients with SLE and APS have antibodies directed against HDL and Apo A-I. A high percentage of these antibodies cross-react with CL, suggesting the presence of different groups of antibodies with different targets. The study of the interaction between the immune response and the lipoprotein components and the correct characterization of the reactivity patterns of autoantibodies may be of relevance in the study of atherosclerosis in patients with SLE and APS.

Adult↗

PubMed1994

Anti-cardiolipin antibodies in autoimmune thyroid diseases.

OBJECTIVE: In recent years anti-phospholipid antibodies have gained much attention since they are frequently associated with thrombosis, recurrent abortion, and thrombocytopenia. Besides disease-specific autoantibodies, other autoantibodies reactive with both organ and non-organ specific autoantigens have been found in patients with autoimmune thyroid diseases. Therefore the objective of this study was to evaluate the presence and significance of anti-phospholipid antibodies in untreated patients with different forms of autoimmune thyroid diseases. PATIENTS AND METHODS: Thirty-one patients (26 females, five males; mean age 42.5 years) affected by different autoimmune thyroid diseases were studied. Fourteen patients were affected by Graves' disease, eight by silent thyroiditis, five by Hashimoto's thyroiditis. Four patients with Graves' disease in remission were also evaluated. Anti-cardiolipin antibodies were detected by enzyme linked immunosorbent assay. In five Graves' disease patients anti-cardiolipin antibodies were evaluated before and after 3 months of therapy with methimazole. RESULTS: Seventeen out of 31 patients were positive for IgG and/or IgM anti-cardiolipin antibodies, the highest levels occurring in three Graves' disease patients with severe thyrotoxicosis. In four of five Graves' patients evaluated before and after methimazole therapy, anticardiolipin antibodies decreased following treatment. None of the patients with increased IgG and/or IgM anticardiolipin antibodies showed clinical manifestations of the anti-phospholipid syndrome during our observation which ranged from 1 to 5 years. CONCLUSIONS: Our results showed an increased incidence of anti-cardiolipin antibodies in patients affected by autoimmune thyroid diseases. However, these autoantibodies seem merely to represent a non-specific marker of immune dysregulation.

Adult↗

PubMed1995

Placental thrombosis and fetal loss after passive transfer of mouse lupus monoclonal or human polyclonal anti-cardiolipin antibodies in pregnant naive BALB/c mice.

In the present study we evaluated the effect of passive transfer of a mouse monoclonal (CAM) or a human polyclonal anti-cardiolipin IgG on pregnancy outcome in BALB/c mice. The mice were immunized through the tail vein immediately after mating with 10 micrograms of monoclonal or polyclonal anti-cardiolipin antibodies. Two other groups of mice were given a mouse irrelevant monoclonal antibody or normal human polyclonal IgG respectively, at the same dose. In mice immunized with monoclonal or polyclonal anti-cardiolipin antibody we observed a significant increase in the number of fetal resorptions and a significant reduction of the mean weights of the embryos and the placentas. In mice immunized with CAM we also found a significant decrease in the number of healthy pups, while mice infused with human aCL antibody expressed a significant reduction in the fecundity rate. The histological examination showed widespread thrombosis and necrosis in the placentas derived from the mice immunized with the anti-cardiolipin antibodies. The model supports a possible direct pathogenetic effect of anti-phospholipid antibodies in recurrent fetal loss and points out that thrombotic events at placental level can be instrumental in the pathogenesis of the obstetric complications.

Animals↗

PubMed2003

[A case of cerebral deep venous and venous sinus thromboses with anti-cardiolipin antibody].

We describe a case of cerebral deep venous and venous sinus thromboses with anti-cardiolipin antibody. A 62-year-old male with no previous illness of thrombosis but with alcohol abuse was admitted with acute onset unconsciousness. He recovered two days after with no severe sequela. Laboratory findings suggested the preceding conditions of dehydration and inflammation. X-ray CT of the head revealed symmetrical low density areas in the thalami and basal ganglia, high density signs in the cerebral deep veins, and dilation of the lateral ventricles. MRI on the second hospital day showed abnormal intensities in the thalami and basal ganglia (high signal on T 2-weighed and FLAIR image, low signals on T 1-weighed image, but almost isointensity on diffusion weighed image) and acute to subacute phase thrombus in the superior sagittal sinus. Abnormal intensities observed on MRI disappeared gradually in the following studies. Venous phase images of cerebral angiography performed in chronic phase disclosed occlusion of the superior sagittal sinus and stenosis of the vein of Galen. These radiological findings support the diagnosis of cerebral deep vein and venous sinus thromboses. Hematological examination revealed positive anti-cardiolipin IgG antibody. Several cases of cerebral deep venous thrombosis with anti-cardiolipin antibody have been reported. In our case, dehydration induced by alcohol abuse would have been the trigger of thrombosis, while the existence of anti-cardiolipin antibody might contribute to the risk of thrombosis as an underlying condition.

Antibodies, Anticardiolipin↗

PubMedDate not supplied

Presence of IgE class antibodies with cardiolipinic and treponemal specificity in syphilis. Quantitative evaluation by IgE prist radio-immuno-assay.

60 serum samples (reactive in VDRL, ELISA-Reiter, FTA-Abs tests) from 25-45 years old male patients with untreated latent syphilis (EL) (30 cases) and persistent positive treated syphilis (ET+) (30 cases) were tested for IgE by IgE-PRIST. On 30 sera from 25-45 years old male healthy persons, normal mean value for serum IgE was established: 159.63 +/- 124.09 U/ml. Cardiolipin and group treponemal IgE fractions were indirectly calculated by the difference between the specific activity induced by sera as such and that induced by sera absorbed with cardiolipin and group treponemal sorbents. In EL, total IgE level was 197 +/- 107 U/ml; cardiolipin IgE -24.9 +/- 8.3 U/ml and group treponemal IgE 35.8 +/- 6.6 U/ml. In ET, total IgE value was 152.6 +/- 122.5 U/ml, cardiolipin IgE -11 +/- 10.5 and group treponemal IgE -26.6 +/- 14.2 U/ml. Summing up the two specificities, the total specific IgE represent about 1/3 from total IgE in EL and 1/5 in ET+. Taking into account the short half-life (2-3 days) of IgE presence of a significant proportion of specific IgE in those two stages proves, by their continuous synthesis paralleling antigenic stimulation, the presence in various tissular zones of viable treponemas as sources of antigens.

Adult↗

PubMed2026

Remodeling of host lipid metabolism by Wolbachia strain wAlbB is associated with lipid accumulation and cardiolipin dysregulation in the Aedes aegypti fat body.

BACKGROUND: The intracellular symbiont Wolbachia, particularly the wAlbB strain, is a promising biocontrol agent against mosquito-borne diseases. Although Wolbachia infection is known to perturb host metabolism, the underlying mechanisms, especially those related to lipid metabolism, remain poorly understood. METHODS: We performed an integrated multi-level analysis of the Aedes aegypti fat body in uninfected and wAlbB-infected mosquitoes, combining histology, biochemistry, untargeted liquid chromatography-mass spectrometry (LC-MS) lipidomics, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enrichment analysis, reverse transcription quantitative PCR of key metabolic genes, and quantification of acetyl-coenzyme A (acetyl-CoA) and reduced nicotinamide adenine dinucleotide (NADH) levels. RESULTS: wAlbB infection increased fat body wet weight and thickness, accompanied by accumulation of triglyceride and of lipid droplets. Lipidomic analysis further revealed extensive lipidome remodeling, with elevated free fatty acid, diglyceride, and triglyceride, but broad depletion of glycerophospholipids, particularly cardiolipin. These changes were supported by transcriptional alterations: upregulation of fatty acid synthase 1 and glycerol-3-phosphate acyltransferase 1, and downregulation of adipose triglyceride lipase and carnitine palmitoyltransferase 1. Cardiolipin depletion correlated with downregulation of genes involved in its synthesis and remodeling, including phosphatidylglycerophosphate synthase and calcium-independent phospholipase A2γ. These lipid changes were also associated with accumulation of acetyl-CoA and NADH. CONCLUSIONS: Our findings suggest that wAlbB infection is associated with extensive lipid metabolic remodeling in the Aedes aegypti fat body, characterized by accumulation of neutral lipids and cardiolipin depletion, accompanied by transcriptional remodeling of key metabolic enzymes. This study establishes the fat body as a primary tissue-level hub for Wolbachia-associated lipid remodeling and provides a foundational framework for future mechanistic investigations into host-symbiont metabolic interactions.

Animals↗