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Fat and sugar overconsumption is the cause of increasing worldwide incidence of gastrointestinal tract in inflammatory conditions. The intestinal pre-inflammatory alterations are partially reversible, simultaneously inhibiting the predisposition to colitis. Searching for an effective pharmacotherapy for treating inflammatory conditions in the intestine is essential. This study aimed to investigate the effect of cannabigerol (CBG) on the inflammation state in the colon tissue of rats subjected to high-caloric diet. The experiment was conducted on male Wistar rats subjected to a standard or a high-fat high-sucrose diets for six weeks. For the last 14 days, half of rats from both groups received intragastrically cannabigerol solution (30â¯mg/kg of body mass). The ratio of n-6/n-3 PUFA, the activity of n-6 and n-3 PUFA, and arachidonic acid (AA) content in selected lipid fractions were determined by gas-liquid chromatography. Immunoblotting examined the expression of proteins involved in inflammation development. ELISA kits measured the content of arachidonic acid derivatives. CBG treatment reduced the n-6/n-3 PUFA ratio in TAG fraction and increased the n-3 PUFA pathway activity in almost all lipid fractions. Cannabigerol supplementation decreased AA concentration in PL and TAG. CBG also caused diminishments in the expression of cPLA2, COX-1, COX-2, and 12/15-LOX, which was indirectly correlated with a decreased LTB4 level and an increased LXA4 level. We concluded that cannabigerol has a protective influence on the development of inflammation in the colon tissue under lipid and sugar overload condition, thereby favoring cancer initiation and progression.
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Numerous strategies have been proposed to minimize obesity-associated health effects, among which phytocannabinoids appear to be effective and safe compounds. In particular, cannabigerol (CBG) emerges as a potent modulator of the composition of membrane phospholipids (PLs), which plays a critical role in the development of insulin resistance. Therefore, here we consider the role of CBG treatment on the composition of PLs fraction with particular emphasis on phospholipid subclasses (e.g., phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS), and phosphatidylinositol (PI)) in the red gastrocnemius muscle of Wistar rats fed the standard or high-fat, high-sucrose (HFHS) diet. The intramuscular PLs content was determined by gas-liquid chromatography and based on the composition of individual FAs, we assessed the stearoyl-CoA desaturase 1 (SCD1) index as well as the activity of n-3 and n-6 polyunsaturated fatty acids (PUFAs) pathways. Expression of various proteins engaged in the inflammatory pathway, FAs elongation, and desaturation processes was measured using Western blotting. Our research has demonstrated the important association of obesity with alterations in the composition of muscular PLs, which was significantly improved by CBG supplementation, enriching the lipid pools in n-3 PUFAs and decreasing the content of arachidonic acid (AA), which in turn influenced the activity of PUFAs pathways in various PLs subclasses. CBG also inhibited the local inflammation development and profoundly reduced the SCD1 activity. Collectively, restoring the PLs homeostasis of the myocyte membrane by CBG indicates its new potential medical application in the treatment of obesity-related metabolic disorders.
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Excessive lipid deposition affects hepatic homeostasis and contributes to the development of insulin resistance as a crucial factor for the deterioration of simple steatosis to steatohepatitis. So, it is essential to search for an effective agent for a new therapy for hepatic steatosis development before it progresses to the more advanced stages. Our study aimed to evaluate the potential protective effect of α-lipoic acid (α-LA) administration on the intrahepatic metabolism of sphingolipid and insulin signaling transduction in rats with metabolic dysfunction-associated steatotic liver disease (MASLD). The experiment was conducted on male Wistar rats subjected to a standard diet or a high-fat diet (HFD) and an intragastrically α-LA administration for eight weeks. High-performance liquid chromatography (HPLC) was used to determine sphingolipid content. Immunoblotting was used to measure the expression of selected proteins from sphingolipid and insulin signaling pathways. Multiplex assay kit was used to assess the level of the phosphorylated form of proteins from PI3K/Akt/mTOR transduction. The results revealed that α-LA decreased sphinganine, dihydroceramide, and sphingosine levels and increased ceramide level. We also observed an increased the concentration of phosphorylated forms of sphingosine and sphinganine. Changes in the expression of proteins from sphingolipid metabolism were consistent with changes in sphingolipid pools. Treatment with α-LA activated the PI3K/Akt/mTOR pathway, which enhanced the hepatic phosphorylation of Akt and mTOR. Based on these data, we concluded that α-lipoic acid may alleviate glucose intolerance and may have a protective influence on the sphingolipid metabolism under HFD; thus, this antioxidant appears to protect from MASLD development and steatosis deterioration.
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Fígado Gorduroso , Fígado , Transdução de Sinais , Esfingolipídeos , Ácido Tióctico , Animais , Masculino , Ratos , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Fígado Gorduroso/metabolismo , Fígado Gorduroso/tratamento farmacológico , Resistência à Insulina , Fígado/metabolismo , Fígado/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Esfingolipídeos/metabolismo , Ácido Tióctico/farmacologia , Serina-Treonina Quinases TOR/metabolismoRESUMO
Adipose derived mesenchymal stem cells (ADMSCs) are a component of adipose tissue that in recent years has gained on importance. The progenitor cells serve as an essentially unlimited source of new adipocytes and therefore are considered to be an important determinant of the tissue's physiology. In this paper we investigated mature adipocytes differentiated from ADMSCs obtained from subcutaneous/visceral fat of patients with different metabolic status (lean, obese without and with metabolic syndrome). We focused our interests on the sphingolipid signaling pathway, i.e.a signal transduction system indispensable for cells functioning, but also implicated in the development of medical conditions associated with obesity. We observed that the cells derived from visceral tissue had significantly greater levels of almost all the examined sphingolipids (especially Cer, dhCer, SM). Moreover, obesity and metabolic syndrome present in donor patients was associated with an increased level of sphingosine kinase (SPHK) and the product of its reaction sphingosine-1-phosphate (S1P). Moreover, the condition appeared to display a tissue specific pattern. Namely, the adipocytes of subcutaneous provenance had an increased activation of ceramide de novo synthesis pathway when the donors of ADMSCs had metabolic syndrome. The above translated into greater accumulation of ceramide in the cells. To our knowledge this is the first study that demonstrated altered sphingolipid profile in the mature adipocytes differentiated from ADMSCs with respect to the stem cells tissue of origin and the donor patient metabolic status.
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Células-Tronco Mesenquimais , Síndrome Metabólica , Obesidade Mórbida , Humanos , Feminino , Síndrome Metabólica/metabolismo , Obesidade Mórbida/metabolismo , Tecido Adiposo/metabolismo , Adipócitos/metabolismo , Esfingolipídeos/metabolismo , Ceramidas/metabolismo , Transdução de Sinais , Células-Tronco Mesenquimais/metabolismoRESUMO
Extracellular sphingosine-1-phosphate (S1P) emerged as an important regulator of muscle function. We previously found that plasma S1P concentration is elevated in response to acute exercise and training. Interestingly, hypoxia, which is commonly utilized in training programs, induces a similar effect. Therefore, the aim of the current study was to determine the effect of normobaric hypoxia on exercise-induced changes in blood sphingolipid metabolism. Fifteen male competitive cyclists performed a graded cycling exercise until exhaustion (GE) and a simulated 30 km individual time trial (TT) in either normoxic or hypoxic (FiO2 = 16.5%) conditions. Blood samples were taken before the exercise, following its cessation, and after 30 min of recovery. We found that TT increased dihydrosphingosine-1-phosphate (dhS1P) concentration in plasma (both HDL- and albumin-bound) and blood cells, as well as the rate of dhS1P release from erythrocytes, regardless of oxygen availability. Plasma concentration of S1P was, however, reduced during the recovery phase, and this trend was augmented by hypoxia. On the other hand, GE in normoxia induced a selective increase in HDL-bound S1P. This effect disappeared when the exercise was performed in hypoxia, and it was associated with reduced S1P level in platelets and erythrocytes. We conclude that submaximal exercise elevates total plasma dhS1P concentration via increased availability of dihydrosphingosine resulting in enhanced dhS1P synthesis and release by blood cells. Maximal exercise, on the other hand, induces a selective increase in HDL-bound S1P, which is a consequence of mechanisms not related to blood cells. We also conclude that hypoxia reduces post-exercise plasma S1P concentration.
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High-fat diet (HFD) contributes to neuroinflammation forming, hence it is crucial to find safe and effective substances that are able to counteract its progress. The anti-inflammatory properties of phytocannabinoids acquired from the Cannabis plant have been widely acknowledged. We evaluated the effects of cannabidiol (CBD) treatment on induced by applying HFD early stages of neuroinflammation in Wistar rat cerebral cortex. In our 7-week experiment, CBD was injected intraperitoneally over the last 14days at a dose of 10 mg/kg of body weight once a day. The level of arachidonic acid, a precursor to pro-inflammatory eicosanoids, decreased in all analysed lipid classes after CBD administration to the HFD group. Moreover, the extent of diminishing the activity of the omega-6 (n-6) fatty acid pathway by CBD was the greatest in diacylglycerols and phospholipids. Surprisingly, CBD was also capable of downregulating the activity of the omega-3 (n-3) pathway. The expression of enzymes involved in the synthesis of the eicosanoids was significantly increased in the HFD group and subsequently lowered by CBD. Significant changes in various cytokines levels were also discovered. Our results strongly suggest the ability of CBD to reduce the formation of lipid inflammation precursors in rat cerebral cortex, as a primary event in the development of neurodegenerative diseases. This can raise hopes for the future use of this cannabinoid for therapeutic purposes since it is a substance lacking lasting and severe side effects.
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Canabidiol , Ratos , Animais , Canabidiol/farmacologia , Doenças Neuroinflamatórias , Ratos Wistar , Dieta Hiperlipídica/efeitos adversos , Fosfolipídeos , Córtex Cerebral , EicosanoidesRESUMO
Ovarian cancer (OC) has emerged as the leading cause of death due to gynecological malignancies among women. Oxidative stress and metalloproteinases (MMPs) have been shown to influence signaling pathways and afflict the progression of carcinogenesis. Therefore, the assessment of matrix-remodeling and oxidative stress intensity can determine the degree of cellular injury and often the severity of redox-mediated chemoresistance. The study group comprised 27 patients with serous OC of which 18% were classified as Federation of Gynecology and Obstetrics (FIGO) stages I/II, while the rest were diagnosed grades III/IV. The control group comprised of 15 ovarian tissue samples. The results were compared with genetic data from The Cancer Genome Atlas. Nitro-oxidative stress, inflammation and apoptosis biomarkers were measured colorimetrically/fluorometrically or via real-time PCR in the primary ovarian tumor and healthy tissue. Stratification of patients according to FIGO stages revealed that high-grade carcinoma exhibited substantial alterations in redox balance, including the accumulation of protein glycoxidation and lipid peroxidation products. TCGA data demonstrated only limited prognostic usefulness of the studied genes. In conclusion, high-grade serous OC is associated with enhanced tissue oxidative/nitrosative stress and macromolecule damage that could not be overridden by the simultaneously augmented measures of antioxidant defense. Therefore, it can be assumed that tumor cells acquire adaptive mechanisms that enable them to withstand the potential toxic effects of elevated reactive oxygen species.
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BACKGROUND: Microand nanoplastics pollution can cause substantial damage to ecosystems. Since scientists have focused mainly on their impact on aquatic environments, less attention has been paid to the accumulation of polymer particles in terrestrial organisms. OBJECTIVES: We checked if submicron (<5 mm) polystyrene (PS) particles, which can accumulate in living organisms, lead to changes in the physicochemical properties of mammalian cell membranes. MATERIAL AND METHODS: The influence of submicron PS particles on the properties of rat-derived L6 myocytes and H9c2 cardiomyocytes was analyzed. Non-functionalized and amine-functionalized PS particles of 100 nm and 200 nm in diameter were used. The MTT assay was performed to evaluate the viability of the polymers-treated cells. The effect of short (6 h) and prolonged (48 h) incubation with different concentrations of PS particles on the cell's zeta (ζ) potential was examined with the electrophoretic light scattering technique (ELS). Polystyrene particles' physicochemical characteristics (size and stability) were performed using dynamic light scattering (DLS) and electrophoretic light scattering methods. RESULTS: The results show that submicron PS particles affect cell viability and cause changes in the physiochemical parameters of rat cell membranes. Differences were observed depending on the origin of the cells. We observed doseand time-dependent alterations in the studied parameters after submicron PS particle incubation in L6 myotubes and H9c2 cardiomyocytes. CONCLUSIONS: The size and modification of PS particle surfaces determine the extent to which they affect the analyzed properties of rat cardiomyocytes and myocytes membranes.
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Sobrevivência Celular , Miócitos Cardíacos , Tamanho da Partícula , Poliestirenos , Animais , Poliestirenos/toxicidade , Poliestirenos/química , Ratos , Sobrevivência Celular/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , Linhagem Celular , Músculo Esquelético/citologia , Músculo Esquelético/efeitos dos fármacos , NanopartículasRESUMO
Diabetes mellitus is a highly prevalent disease characterized by hyperglycaemia that damages the vascular system, leading to micro- (retinopathy, neuropathy, nephropathy) and macrovascular diseases (cardiovascular disease). There are also secondary complications of diabetes (cardiomyopathy, erectile dysfunction or diabetic foot ulcers). Stem cell-based therapies have become a promising tool targeting diabetes symptoms and its chronic complications. Among all stem cells, adipose-derived mesenchymal stem cells (ADMSCs) are of great importance because of their abundance, non-invasive isolation and no ethical limitations. Characteristics that make ADMSCs good candidates for cell-based therapy are their wide immunomodulatory properties and paracrine activities through the secretion of an array of growth factors, chemokines, cytokines, angiogenic factors and anti-apoptotic molecules. Besides, after transplantation, ADMSCs show great ex vivo expansion capacity and differentiation to other cell types, including insulin-producing cells, cardiomyocytes, chondrocytes, hepatocyte-like cells, neurons, endothelial cells, photoreceptor-like cells, or astrocytes. Preclinical studies have shown that ADMSC-based therapy effectively improved visual acuity, ameliorated polyneuropathy and foot ulceration, arrested the development and progression of diabetic kidney disease, or alleviated the diabetes-induced cardiomyocyte hypertrophy. However, despite the positive results obtained in animal models, there are still several challenges that need to be overcome before the results of preclinical studies can be translated into clinical applications. To date, there are several clinical trials or ongoing trials using ADMSCs in the treatment of diabetic complications, most of them in the treatment of diabetic foot ulcers. This narrative review summarizes the most recent outcomes on the usage of ADMSCs in the treatment of long-term complications of diabetes in both animal models and clinical trials.
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Diabetes Mellitus , Pé Diabético , Hiperglicemia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Masculino , Animais , Tecido Adiposo/metabolismo , Pé Diabético/terapia , Células Endoteliais , Células-Tronco Mesenquimais/metabolismo , Hiperglicemia/terapia , Transplante de Células-Tronco Mesenquimais/métodos , Diabetes Mellitus/metabolismoRESUMO
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent liver disorder affecting a significant part of the global population. This study aimed to investigate the potential therapeutic effects of α-lipoic acid (α-LA) on the inflammatory response during simple steatosis development and progression into steatohepatitis. The study used the MASLD model in male Wistar rats that were fed a standard diet or a high-fat diet (HFD) for 8 weeks. Throughout the entire experiment, half of the animals received α-LA supplementation. The hepatic activity of pro-inflammatory n-6 and anti-inflammatory n-3 polyunsaturated fatty acid (PUFA) pathways and the concentration of arachidonic acid (AA) in selected lipid fractions were determined by the gas-liquid chromatography (GLC). The hepatic expression of proteins from inflammatory pathway was measured by the Western blot technique. The level of eicosanoids, cytokines and chemokines was assessed by the ELISA or multiplex assay kits. The results showed that α-LA supplementation attenuated the activity of n-6 PUFA pathway in FFA and DAG and increased the activity of n-3 PUFA pathway in PL, TAG and DAG. In addition, the administration of α-LA decreased the concentration of AA in DAG and FFA, indicating its potential protective effect on the deterioration of simple hepatic steatosis. The supplementation of α-LA also increased the expression of COX-1 and COX-2 with the lack of significant changes in prostaglandins profile. We observed an increase in the expression of 12/15-LOX, which was reflected in an increase in lipoxin A4 (LXA4) level. A decrease in pro-inflammatory cytokines and an increase in anti-inflammatory cytokines was also noticed in the liver of rats treated with HFD and α-LA. Our observations confirm that α-LA treatment has potential protective effects on inflammation development in the MASLD model. We believe that α-LA has a preventive impact when it comes to the progression of simple steatosis lesions to steatohepatitis.
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Fígado Gorduroso , Ácido Tióctico , Ratos , Masculino , Animais , Ácido Tióctico/farmacologia , Ácido Tióctico/uso terapêutico , Ácido Tióctico/metabolismo , Dieta Hiperlipídica/efeitos adversos , Ratos Wistar , Fígado Gorduroso/metabolismo , Fígado Gorduroso/patologia , Fígado Gorduroso/prevenção & controle , Fígado/metabolismo , Inflamação/tratamento farmacológico , Inflamação/prevenção & controle , Inflamação/metabolismo , Anti-Inflamatórios/farmacologia , Citocinas/metabolismoRESUMO
The Omega-3 Index (O3I) reflects eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) content in erythrocytes. While the O3I is associated with numerous health outcomes, its widespread use is limited. We investigated whether urinary metabolites could be used to non-invasively monitor the O3I in an exploratory analysis of a previous placebo-controlled, parallel arm randomized clinical trial in males and females (n = 88) who consumed either ~3 g/d olive oil (OO; control), EPA, or DHA for 12 weeks. Fasted blood and first-void urine samples were collected at baseline and following supplementation, and they were analyzed via gas chromatography and multisegment injection-capillary electrophoresis-mass spectrometry (MSI-CE-MS), respectively. We tentatively identified S-carboxypropylcysteamine (CPCA) as a novel urinary biomarker reflecting O3I status, which increased following both EPA and DHA (p < 0.001), but not OO supplementation, and was positively correlated to the O3I (R = 0.30, p < 0.001). Additionally, an unknown dianion increased following DHA supplementation, but not EPA or OO. In ROC curve analyses, CPCA outperformed all other urinary metabolites in distinguishing both between OO and EPA or DHA supplementation groups (AUC > 80.0%), whereas the unknown dianion performed best in discriminating OO from DHA alone (AUC = 93.6%). Candidate urinary biomarkers of the O3I were identified that lay the foundation for a non-invasive assessment of omega-3 status.
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BACKGROUND: Cannabigerol (CBG), a non-psychotropic phytocannabinoid found in Cannabis sativa plants, has been the focus of recent studies due to its potential therapeutic properties. We proposed that by focusing on sphingolipid metabolism, which plays a critical role in insulin signaling and the development of insulin resistance, CBG may provide a novel therapeutic approach for metabolic disorders, particularly insulin resistance. METHODS: In a rat model of insulin resistance induced by a high-fat, high-sucrose diet (HFHS), we aimed to elucidate the effect of intragastrically administered CBG on hepatic sphingolipid deposition and metabolism. Moreover, we also elucidated the expression of sphingolipid transporters and changes in the sphingolipid concentration in the plasma. RESULTS: The results, surprisingly, showed a lack of changes in de novo ceramide synthesis pathway enzymes and significant enhancement in the expression of enzymes involved in ceramide catabolism, which was confirmed by changes in hepatic sphingomyelin, sphinganine, sphingosine-1-phosphate, and sphinganine-1-phosphate concentrations. CONCLUSIONS: The results suggest that CBG treatment may modulate sphingolipid metabolism in the liver and plasma, potentially protecting the liver against the development of metabolic disorders such as insulin resistance.
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Resistência à Insulina , Esfingolipídeos , Ratos , Animais , Esfingolipídeos/metabolismo , Insulina/metabolismo , Fígado/metabolismo , Ceramidas/metabolismoRESUMO
Psoriasis is a chronic, complex, immunological disorder, which may lead to many different systemic complications. Sphingolipids, including ceramide, are bioactive lipids, which take part in the regulation of immune reactions, cell growth, and apoptosis. Twenty psoriatic patients and twenty-eight control subjects were included in the study. Skin (both lesional and non-lesional) and serum samples were collected from both the control group and the psoriatic patients. The levels of sphingosine (SFO), sphingosine-1-phosphate (S1P), sphingomyelin, sphinganine (SFA), sphinganine-1-phosphate (SFA1P), and ceramide (CER) were assessed in both tissue (t) and serum (s) samples using high-performance liquid chromatography (HPLC). We identified elevated serum levels of SFO, S1P, SFA, and SFA1P in psoriatic patients when compared to healthy individuals. As far as the lesional skin and serum of psoriatic patients are concerned, we demonstrated positive associations between CER_t and CER_s, SFA_t and CER_s, and SFO_t and CER_s. Additionally, we found negative correlations in the non-lesional skin and serum of psoriatic patients, including SFO_t vs. SFO_s, CER_t vs. SFA_s, CER_t vs. SFO_s, and SFO_t vs. SFA_s. Finally, we observed a positive correlation between S1P and SFA1P in both the serum samples of psoriatic patients and the serum samples of the control group. In this study, we did not observe any correlations between psoriasis area and severity index (PASI) scores and sphingolipid levels. In conclusion, our findings indicate an interplay between skin and serum lipids in psoriatic patients, which is not observed in healthy individuals.
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Psoríase , Esfingolipídeos , Humanos , Ceramidas , Pele , EsfingosinaRESUMO
Hepatic fibrosis is a consequence of liver injuries, in which the overproduction and progressive accumulation of extracellular matrix (ECM) components with the simultaneous failure of matrix turnover mechanisms are observed. The aim of this study was to investigate the concentration-dependent influence of cannabigerol (CBG, Cannabis sativa L. component) on ECM composition with respect to transforming growth factor beta 1 (TGF-ß1) changes in primary hepatocytes with fibrotic changes induced by palmitate and fructose media. Cells were isolated from male Wistar rats' livers in accordance with the two-step collagenase perfusion technique. This was followed by hepatocytes incubation with the presence or absence of palmitate with fructose and/or cannabigerol (at concentrations of 1, 5, 10, 15, 25, 30 µM) for 48 h. The expression of ECM mRNA genes and proteins was determined using PCR and Western blot, respectively, whereas media ECM level was evaluated using ELISA. Our results indicated that selected low concentrations of CBG caused a reduction in TGF-ß1 mRNA expression and secretion into media. Hepatocyte exposure to cannabigerol at low concentrations attenuated collagen 1 and 3 deposition. The protein and/or mRNA expressions and MMP-2 and MMP-9 secretion were augmented using CBG. Considering the mentioned results, low concentrations of cannabigerol treatment might expedite fibrosis regression and promote regeneration.
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Endothelial (EL) and lipoprotein (LPL) lipases are enzymes involved in lipoproteins metabolism and formation of atherosclerosis, a pathological feature of coronary artery disease (CAD). This paper examines the role of the lipases in the right atrial appendage (RAA) and coronary perivascular adipose tissue (PVAT) of patients with CAD alone or with accompanying diabetes. Additionally, correlation analysis for plasma concentration of the lipases, apolipoproteins (ApoA-ApoJ) and blood lipids (Chol, HDL-C, LDL-C, TAG) was performed. We observed that CAD had little effect on the lipases gene/protein levels in the RAA, while their transcript content was elevated in the PVAT of diabetic CAD patients. Interestingly, the RAA was characterized by higher expression of EL/LPL (EL: +1-fold for mRNA, +5-fold for protein; LPL: +2.8-fold for mRNA, +12-fold for protein) compared to PVAT. Furthermore, ApoA1 plasma concentration was decreased, whereas ApoC1 and ApoH were increased in the patients with CAD and/or diabetes. The concentrations of ApoC3 and ApoD were strongly positively correlated with TAG content in the blood, and the same was true for ApoB with respect to LDL-C and total cholesterol. Although plasma concentrations of EL/LPL were elevated in the patients with diabetes, CAD alone had little effect on blood, myocardial and perivascular fat expression of the lipases.
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Fibrilação Atrial , Doença da Artéria Coronariana , Diabetes Mellitus , Humanos , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/genética , Lipase Lipoproteica/genética , LDL-Colesterol , Miocárdio , Átrios do Coração , LipaseRESUMO
The study explored the potential protective influence of cannabidiol (CBD) on myocardial inflammation state, with a special focus on arachidonic acid (AA), and oxidative balance in lipid overload conditions. The 7-week experiment was conducted on male Wistar rats receiving standard or high-fat diet (HFD) with intraperitoneal CBD injections for the last 14 days. The n-3 and n-6 polyunsaturated fatty acids (PUFAs) activities and AA concentration in selected fractions were evaluated by gas-liquid chromatography (GLC). The expression of proteins was determined by Western blot and the concentration of different parameters by ELISA, colorimetric, or multiplex assay kits. Our results revealed that CBD increased n-3 PUFAs activity in phospholipid and triacylglycerol fractions, and decreased AA content in the HFD group, especially in the phospholipid pool. Simultaneously, CBD decreased the expression of nuclear factor kappa B, cyclooxygenase-1, and - 2, resulting in the reduction of prostaglandin E2 and the increment of prostaglandin I2. CBD appears to be relatively safe for the treatment of obesity-induced heart disease, as it has anti-inflammatory and partially antioxidative properties.
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Canabidiol , Ratos , Masculino , Animais , Ácido Araquidônico , Canabidiol/farmacologia , Canabidiol/uso terapêutico , Ratos Wistar , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Ácidos Graxos Ômega-6 , FosfolipídeosRESUMO
The Akt substrate of 160 kDa (AS160), also known as TBC1 domain family member 4 (TBC1D4), represents a crucial regulator of insulin-stimulated glucose uptake in skeletal muscle and adipose tissue. Recent evidence suggests that AS160/TBC1D4 may also control the cellular entry of long-chain fatty acids (LCFAs), resulting in changes to the lipid profile of muscles and fat cells in lean subjects. However, there are virtually no data on AS160/TBC1D4 expression and its modulatory role in lipid metabolism in the adipocytes from morbidly obese individuals of different metabolic status. In this study, we evaluated the effect of the three main factors, i.e., AS160 silencing, obesity, and metabolic syndrome on lipid uptake and profile in fully differentiated adipocytes derived from mesenchymal stem cells (ADMSCs) of lean and obese (with/without metabolic syndrome) postmenopausal women. Additionally, we tested possible interactions between the explanatory variables. In general, obesity translated into a greater content of fatty acid transporters (especially CD36/SR-B2 and SLC27A4/FATP4) and boosted accumulation of all the examined lipid fractions, i.e., triacylglycerols (TAGs), diacylglycerols (DAGs), and free fatty acids (FFAs). The aforementioned were further enhanced by metabolic syndrome. Moreover, AS160 deficiency also increased the abundance of SLC27A4/FATP4 and CD36/SR-B2, especially on the cell surface of the adipocytes derived from ADMSCs of subcutaneous deposit. This was further accompanied by increased LCFA (palmitic acid) uptake. Despite the aforementioned, AS160 silencing seemed unable to significantly affect the phenotype of the adipocytes stemming from obese patients with respect to their cellular lipid profile as we observed virtually no changes in TAG, DAG, and FFA contents when compared to cells with the reference level of proteins. Nevertheless, knockdown of AS160 stimulated fatty acid oxidation, which may indicate that adaptive mechanisms counteract excessive lipid accumulation. At the same time, adipocytes of visceral origin were rather insensitive to the applied intervention.
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Psoriasis is a complex chronic immunologically mediated disease that may involve skin, nails, and joints. It is characterized by hyperproliferation, deregulated differentiation, and impaired apoptosis of keratinocytes. Sphingolipids, namely ceramide, sphingosine-1-phosphate, sphingosine, sphingomyelin, and sphinganine-1-phosphate, are signal molecules that may regulate cell growth, immune reactions, and apoptosis. Fifteen patients with psoriasis and seventeen healthy persons were enrolled in the study. Skin samples were taken from psoriatic lesions and non-lesional areas. Tissue concentration of ceramides, sphingosine-1-phosphate, sphingosine, sphingomyelin, and sphinganine-1-phosphate was measured by liquid chromatography. We assessed that all levels of ceramides, sphingosine-1-phosphate, sphingosine, sphingomyelin, and sphinganine-1-phosphate were higher in lesioned psoriatic skin than in non-affected skin. The profile of bioactive lipids in the lesional skin of patients with psoriasis differed significantly from non-involved psoriatic skin and skin in healthy subjects.
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Psoríase , Esfingolipídeos , Humanos , Esfingosina , Esfingomielinas , Ceramidas/química , FosfatosRESUMO
Psoriasis is a chronic, systematic, inflammatory disease in which multiple metabolic and immunologic disturbances lead to lipid abnormalities, impaired glucose tolerance, metabolic syndrome, diabetes mellitus, atherosclerosis, hypertension, ischemic heart disease, and numerous metabolic disorders. In clinical practice, the most commonly used drugs in the treatment of lipid abnormalities are statins and fibrates. Statins are characterized by pleiotropic effects such as antioxidant, anti-inflammatory, anticoagulant, and antiproliferative. They work by reducing the concentrations of low-density lipoprotein (LDL), total cholesterol, and triglycerides and stabilizing atherosclerotic plaque. Fibrates are medications, which help to lower triglycerides, LDL, very low-density lipoprotein (VLDL) levels and increase lower high-density lipoprotein (HDL). In recent years, many new drugs were found to normalize the lipid profile in patients with psoriasis: glitazones (pioglitazone, troglitazone), and glucagon-like peptide-1 (GLP-1) receptor agonists. Pioglitazone improves the lipid profile, including the decrease of triglycerides, fatty acids, and LDL, as well as the increase of HDL. Glucagon-like peptide 1 (GLP-1) analogs decrease modestly low-density lipoprotein cholesterol (LDL-C), total cholesterol, and triglycerides. The purpose of this study is to assess the current state of knowledge on the effect of different hypolipidemic treatments on the course of psoriasis. The study includes literature from medical databases PubMed and Google Scholar. We were browsing PubMed and Google Scholar until the beginning of December. The systematic review includes 41 eligible original articles.
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The Δ-6 desaturase (D6D) enzyme is not only critical for the synthesis of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from α-linolenic acid (ALA), but recent evidence suggests that it also plays a role in adipocyte lipid metabolism and body weight; however, the mechanisms remain largely unexplored. The goal of this study was to investigate if a D6D deficiency would inhibit triacylglycerol storage and alter lipolytic and lipogenic pathways in mouse white adipose tissue (WAT) depots due to a disruption in EPA and DHA production. Male C57BL/6J D6D knockout (KO) and wild-type (WT) mice were fed either a 7% w/w lard or flax (ALA rich) diet for 21 weeks. Energy expenditure, physical activity, and substrate utilization were measured with metabolic caging. Inguinal and epididymal WAT depots were analyzed for changes in tissue weight, fatty acid composition, adipocyte size, and markers of lipogenesis, lipolysis, and insulin signaling. KO mice had lower body weight, higher serum nonesterified fatty acids, smaller WAT depots, and reduced adipocyte size compared to WT mice without altered food intake, energy expenditure, or physical activity, regardless of the diet. Markers of lipogenesis and lipolysis were more highly expressed in KO mice compared to WT mice in both depots, regardless of the diet. These changes were concomitant with lower basal insulin signaling in WAT. Collectively, a D6D deficiency alters triacylglycerol/fatty acid cycling in WAT by promoting lipolysis and reducing fatty acid re-esterification, which may be partially attributed to a reduction in WAT insulin signaling.