Inflammatory changes in perivascular adipose tissue are associated with atherosclerotic lesions in the adjacent artery and can also be used as a marker in patient workup. While adipocyte size is known to be closely related to adipose tissue dysfunction and inflammation, it has not been widely studied in perivascular adipose tissue obtained from healthy human subjects without clinical atherosclerosis. In this cross-sectional study, we addressed this issue by measuring adipocyte size and defining its relationship to cardiovascular risk factors in a healthy cohort of living kidney donors. The presence of cardiovascular risk factors was established by a standardized questionnaire, clinical measurements and body composition analyses. Adipocyte size was measured in the perivascular depot. The proportions of various macrophage subtypes were determined by flow cytometry. To confirm the results, the proportion of CD68 + macrophages was additionally assessed by immunohistochemistry. A correlation and principal component analyses were performed to explore associations. Adipocyte size in perivascular adipose tissue correlated with markers of lipid metabolism, inflammation, and glucose metabolism. Further, the positive correlation with the pro-inflammatory subpopulation of macrophages suggests a strong local effect of perivascular adipose tissue. Perivascular adipocyte size was associated with cardiovascular risk factors and markers of inflammation in a healthy cohort of living kidney donors. This further supports the local role of adipose tissue dysfunction and inflammation in early atherosclerosis development and detection.
- Klíčová slova
- Perivascular adipose tissue, adipocyte size, cardiovascular risk factors, inflammation, macrophages,
- MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- lipidy * MeSH
- makrofágy metabolismus MeSH
- metabolismus lipidů MeSH
- průřezové studie MeSH
- tuková tkáň metabolismus MeSH
- tukové buňky * metabolismus cytologie MeSH
- velikost buňky MeSH
- zánět * metabolismus patologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- lipidy * MeSH
INTRODUCTION: Depression therapy has been linked to negative effects on energy metabolism, which can be attributed to various factors, including an ongoing inflammatory process commonly seen in metabolic disorders. Unhealthy lifestyle choices of patients and the impact of antidepressants on body weight and lipid and glucose metabolism also contribute to these metabolic side effects. Although not as pronounced as other psychopharmaceuticals, the increasing use of antidepressants raises concerns about their potential impact on public health. The study aimed to evaluate the short- and long-term effects of the antidepressant citalopram and its long-term combination with a special diet on metabolic parameters in mice. METHODS: Animals were randomly divided into 5 groups - control, control + special diet, citalopram (10 mg/kg for 35 days), citalopram + special diet (10 mg/kg for 35 days), and citalopram (10 mg/kg for 7 days). After a described time of administration, animals were anesthetized, blood and fat and liver tissues were collected. Biochemical parameters of lipid metabolism (total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides) and glucose were analyzed using spectrophotometry and relevant adipokines and cytokines were evaluated by ELISA. RESULTS: After a week of application of citalopram, we observed dyslipidemia that persisted even at the end of the 5-week experiment. Furthermore, after 5 weeks of citalopram administration, we observed a significant decrease in body weight gain and decreased leptin levels. Changes in lipid metabolism, higher levels of adipokines leptin and PAI-1 were observed due to the special diet after 5 weeks. CONCLUSIONS: Our research suggests that the effects of citalopram and a diet on the metabolism of mice can be significant, both in the short term (1 week) and in the long term (5 weeks).
- Klíčová slova
- Adipokines, Citalopram, Dyslipidemia, Leptin, Metabolic syndrome, Mouse,
- MeSH
- citalopram * škodlivé účinky aplikace a dávkování farmakologie MeSH
- dieta s vysokým obsahem tuků škodlivé účinky MeSH
- dyslipidemie * chemicky indukované krev metabolismus MeSH
- glukosa * metabolismus MeSH
- játra metabolismus účinky léků MeSH
- krevní glukóza metabolismus účinky léků MeSH
- leptin * krev metabolismus MeSH
- lipidy * krev MeSH
- metabolismus lipidů * účinky léků MeSH
- myši MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- citalopram * MeSH
- glukosa * MeSH
- krevní glukóza MeSH
- leptin * MeSH
- lipidy * MeSH
Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) plays a crucial role in regulation of metabolic homeostasis. To understand the role of the catalytic α2 subunit of AMPK in skeletal muscle energy metabolism, myotube cultures were established from AMPKα2+/+ and AMPKα2-/- mice. Myotubes from AMPKα2-/- mice had lower basal oleic acid and glucose oxidation compared to myotubes from AMPKα2+/+ mice. However, the relative response to mitochondrial uncoupling was increased for oleic acid oxidation. Incorporation of acetate into lipids was also lower in myotubes from AMPKα2-/- mice. Proteomics analysis revealed that AMPKα2-/- myotubes had upregulated pathways related to mitochondrial function and fatty acid oxidation, and decreased pathways related to fatty acid biosynthesis. In conclusion, ablation of AMPKα2 catalytic subunit in skeletal muscle cells resulted in reduced basal oxidation of glucose and fatty acids, however upregulated pathways related to mitochondrial function and fatty acid oxidation and reduced lipid formation.
- Klíčová slova
- AMPK, energy metabolism, oxidative phosphorylation, skeletal muscle,
- MeSH
- energetický metabolismus MeSH
- glukosa * metabolismus MeSH
- kosterní svalová vlákna * metabolismus cytologie MeSH
- kosterní svaly metabolismus MeSH
- kultivované buňky MeSH
- mastné kyseliny metabolismus MeSH
- metabolismus lipidů * MeSH
- mitochondrie metabolismus MeSH
- myši knockoutované MeSH
- myši MeSH
- oxidace-redukce MeSH
- proteinkinasy aktivované AMP * genetika metabolismus nedostatek MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- glukosa * MeSH
- mastné kyseliny MeSH
- Prkaa2 protein, mouse MeSH Prohlížeč
- proteinkinasy aktivované AMP * MeSH
Metabolic-dysfunction associated steatotic liver disease (MASLD) affects approximately 30 % of the world adult population and even contributes to the increased mortality from cardiovascular disease. Dietary intervention, along with exercise, is the most important tool for the treatment of MASLD patients. Dietary composition can have profound effects on liver fat. This review summarizes the results of studies that used MR methods to study the effect of macronutrients on liver fat content. It focuses on intervention studies manipulating the content and quantity of macronutrients in long-term dietary intervention studies and, in more detail, on studies monitoring the effect of administered nutrients on changes in liver fat over several hours.
The ever-increasing use of chemicals and the rising incidence of adverse reproductive effects in the modern environment have become an emerging concern. Several studies have shown that environmental contaminants, such as organophosphate flame retardants (OPFRs), negatively impact reproductive health. To evaluate the potential endocrine-related adverse reproductive effects of widely used and priority-listed compound 2-Ethylhexyl diphenyl phosphate (EHDPP), we characterized its effects on adrenal steroidogenesis in human adrenocortical (H295R) cells. The cells were exposed to EHDPP (1 and 5 μM) for 48 h, and the production of hormones, including progesterone, androstenedione, testosterone, estradiol, cortisol, and aldosterone, was measured. In addition, LC-MS/MS-based lipidomics analysis was done to quantify intracellular lipid profiles, and transcriptional assays were performed to examine the expression of genes related to corticosteroidogenesis, lipid metabolism, and mitochondrial dynamics. Our findings indicate that EHDPP disrupts hormone regulation in vitro, as evidenced by increased estradiol, cortisol, and aldosterone secretion. The expression of key corticosteroidogenic genes (CYP11B2, CYP21A1, 3β-HSD2, and 17β-HSD1) was upregulated significantly upon EHDPP exposure. Intracellular lipidomics revealed EHDPP-mediated disruption, including reduced total cholesterol ester, sphingolipids, and increased phospholipids, triglyceride species, and saturated-monounsaturated lipids subspecies. These alterations were accompanied by decreased ACAT2 and SCD1 gene expression. Moreover, a shift in mitochondrial dynamics was indicated by increased MF1 expression and decreased FIS1 expression. These data suggest that EHDPP disrupts adrenal steroidogenesis and lipid homeostasis, emphasizing its potential endocrine-disrupting effects.
- MeSH
- lidé MeSH
- lipidomika MeSH
- metabolismus lipidů * účinky léků MeSH
- nadledviny * účinky léků metabolismus cytologie MeSH
- organofosfáty * farmakologie MeSH
- steroidy * biosyntéza MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- organofosfáty * MeSH
- steroidy * MeSH
Significance: Type 2 diabetes as a world-wide epidemic is characterized by the insulin resistance concomitant to a gradual impairment of β-cell mass and function (prominently declining insulin secretion) with dysregulated fatty acids (FAs) and lipids, all involved in multiple pathological development. Recent Advances: Recently, redox signaling was recognized to be essential for insulin secretion stimulated with glucose (GSIS), branched-chain keto-acids, and FAs. FA-stimulated insulin secretion (FASIS) is a normal physiological event upon postprandial incoming chylomicrons. This contrasts with the frequent lipotoxicity observed in rodents. Critical Issues: Overfeeding causes FASIS to overlap with GSIS providing repeating hyperinsulinemia, initiates prediabetic states by lipotoxic effects and low-grade inflammation. In contrast the protective effects of lipid droplets in human β-cells counteract excessive lipids. Insulin by FASIS allows FATP1 recruitment into adipocyte plasma membranes when postprandial chylomicrons come late at already low glycemia. Future Directions: Impaired states of pancreatic β-cells and peripheral organs at prediabetes and type 2 diabetes should be revealed, including the inter-organ crosstalk by extracellular vesicles. Details of FA/lipid molecular physiology are yet to be uncovered, such as complex phenomena of FA uptake into cells, postabsorptive inactivity of G-protein-coupled receptor 40, carnitine carrier substrate specificity, the role of carnitine-O-acetyltransferase in β-cells, and lipid droplet interactions with mitochondria. Antioxid. Redox Signal. 42, 566-622.
- Klíčová slova
- fatty acid-stimulated insulin secretion, insulin resistance, lipotoxicity, pancreatic beta cells, type-2 diabetes,
- MeSH
- beta-buňky metabolismus MeSH
- diabetes mellitus 2. typu metabolismus MeSH
- glukosa metabolismus MeSH
- inzulin * metabolismus MeSH
- inzulinová rezistence MeSH
- lidé MeSH
- mastné kyseliny * metabolismus MeSH
- metabolismus lipidů MeSH
- oxidace-redukce MeSH
- sekrece inzulinu MeSH
- signální transdukce * MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- glukosa MeSH
- inzulin * MeSH
- mastné kyseliny * MeSH
BACKGROUND: Low levels of vitamin D have been associated with several autoimmune diseases. A growing body of evidence supports the association of vitamin D with skeletal muscle damage, regeneration, and energy and lipid metabolism. The aim was to analyse vitamin D and its receptor (VDR) in the muscle tissue of patients with idiopathic inflammatory myopathies (IIM) and to relate them to clinical parameters and muscle lipid and energy metabolism. METHODS: Forty-six patients with IIM and 67 healthy controls (HC) were included in the study. 27 IIM patients participated in a 24-week exercise intervention. Muscle biopsies were obtained from 7 IIM patients before/after training, 13 non-exercising IIM controls, and 21 HC. Circulating concentrations of 25(OH)D and 1,25(OH)D were measured. Gene expression of VDR and CYP27B1, the enzyme converting 25(OH)D to hormonally active 1,25(OH)D, was determined by qPCR in muscle tissue and primary muscle cells. Lipid oxidative metabolism was assessed in muscle tissue (mRNA, qPCR) and primary muscle cells (radioactive assays). RESULTS: Lower levels of active 1,25(OH)D were observed in IIM patients compared with HC (mean ± SD: 125.0 ± 45.4 vs. 164.7 ± 49.2 pmol/L; p < 0.0001). 25(OH)D was associated with CRP (r = -0.316, p = 0.037), MITAX (r = -0.311, p = 0.040) and HAQ (r = -0.390, p = 0.009) in IIM. After 24 weeks of training, active 1,25(OH)D was associated with MMT8 (r = 0.866, p < 0.0001), FI-2 (r = 0.608, p = 0.013) and HAQ (r = -0.537, p = 0.032). Gene expression of both VDR and CYP27B1 in primary muscle cells decreased after training (p = 0.031 and p = 0.078, respectively). Associations of VDR mRNA in muscle tissue with MMT-8 (IIM: r = -0.559, p = 0.013), serum CK (HC: r = 0.484, p = 0.031), myoglobin (IIM: r = 0.510, p = 0.026) and myostatin (IIM: r = -0.519, p = 0.023) were observed. The expression of VDR in differentiated muscle cells correlated negatively with the complete oxidation of palmitic acid (r = -0.532, p = 0.028). Muscle mRNA of carnitine palmitoyl transferase 1 (CPT1) (downregulated in IIM, p = 0.001) correlated positively with serum 1,25(OH) vitamin D (r = 0.410, p = 0.042). CONCLUSION: Reduced biologically active vitamin D in circulation suggests its impaired metabolism in IIM. Serum vitamin D levels and gene expression of its receptor and activating enzyme in muscle tissue were modified by regular exercise and associated with disease manifestations, physical fitness, and muscle lipid metabolism of IIM patients.
- Klíčová slova
- Lipid metabolism, Mitochondria, Muscle, Myositis, Physical activity, Vitamin D,
- MeSH
- 1-alfa-hydroxylasa 25-hydroxyvitaminu D3 MeSH
- cvičení fyziologie MeSH
- dospělí MeSH
- kosterní svaly * metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- metabolismus lipidů * fyziologie MeSH
- myozitida * metabolismus MeSH
- receptory kalcitriolu * metabolismus genetika MeSH
- senioři MeSH
- tělesná výkonnost * fyziologie MeSH
- vitamin D * metabolismus krev analogy a deriváty MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- 1-alfa-hydroxylasa 25-hydroxyvitaminu D3 MeSH
- CYP27B1 protein, human MeSH Prohlížeč
- receptory kalcitriolu * MeSH
- VDR protein, human MeSH Prohlížeč
- vitamin D * MeSH
Chlorinated paraffins (CPs) are environmental pollutants extensively used in industries. While the use of short-chain chlorinated paraffins (SCCPs) has been restricted since 2017, the use of medium-chain chlorinated paraffins (MCCPs) has risen as their replacement. Due to lipophilic character, it can be expected that CPs enter the cells; however, the in vitro accumulation potential of CPs remains poorly understood. In this study, we aimed to explore the ability of SCCPs and MCCPs to accumulate in fat cells. We utilized an in vitro model of mouse 3T3-L1 preadipocytes and adipocytes. Using gas chromatography coupled with high-resolution mass spectrometry operated in negative chemical ionization mode, we determined the intracellular amounts of CPs. These compounds accumulated at rates of 8.5 ± 0.1 µg/gcells/h for SCCPs and 7.8 ± 0.3 µg/gcells/h for MCCPs when an initial concentration of 120 ng/ml was present in the medium. This rate increased approximately tenfold when the concentration of CPs was raised to 1200 ng/ml. CPs content in adipocytes steadily increased over 5 days, whereas preadipocytes accumulated 15-20 times less CPs. This highlights the importance of cellular lipid content, which was about 12 times higher in adipocytes. Furthermore, we found that the level of chlorine content in the CPs molecules significantly influenced their accumulation. Our results demonstrate that MCCPs exhibit a similar accumulation potential to SCCPs, with lipid content playing a crucial role. As with SCCPs, restrictions on the use of MCCPs in industry should be considered to mitigate their environmental and health impacts.
- Klíčová slova
- 3T3-L1 cells, Adipocytes, Chlorinated paraffins, Persistent organic pollutants,
- MeSH
- buňky 3T3-L1 MeSH
- chlorované uhlovodíky * metabolismus toxicita MeSH
- halogenace MeSH
- látky znečišťující životní prostředí * metabolismus toxicita MeSH
- lipidy analýza MeSH
- metabolismus lipidů * účinky léků MeSH
- myši MeSH
- parafín * metabolismus toxicita chemie MeSH
- plynová chromatografie s hmotnostně spektrometrickou detekcí MeSH
- tukové buňky * metabolismus účinky léků MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- chlorované uhlovodíky * MeSH
- látky znečišťující životní prostředí * MeSH
- lipidy MeSH
- parafín * MeSH
Endocrine-disrupting chemicals (EDCs) may contribute to the rising incidence of metabolic dysfunction-associated steatotic liver disease (MASLD). We investigated the potential of 10 environmentally relevant EDCs to affect key events of hepatic steatosis in HepG2 human hepatoblastoma cells. Increased lipid droplet formation, a key marker of steatosis, was induced by PFOA, bisphenol F, DDE, butylparaben, and DEHP, within the non-cytotoxic concentration range of 1 nM-25 μM. Cadmium also induced this effect, but at concentrations impairing cell viability (>1 μM). At non-cytotoxic concentrations, these compounds, along with bisphenol A, dysregulated major genes controlling lipid homeostasis. Cadmium, PFOA, DDE, and DEHP significantly upregulated the DGAT1 gene involved in triglyceride synthesis, while butylparaben increased the expression of the FAT/CD36 gene responsible for fatty acid uptake. Bisphenol A downregulated the CPT1A gene involved in fatty acid oxidation. No significant effects on lipid droplet accumulation or lipid metabolism-related genes were observed for PFOS, bisphenol S, and dibutyl phthalate. Among the tested EDCs, lipid accumulation positively correlated with the expression of SREBF1, DGAT1, and CPT1A. These findings provide additional evidence that EDCs can affect MASLD and highlight the utility of in vitro methods in the screening of EDCs with hazardous steatogenic and metabolism-disrupting properties.
- Klíčová slova
- High-content imaging, In vitro testing, Lipid droplets, Metabolism-disrupting chemicals, NAFLD, NAMs,
- MeSH
- benzhydrylové sloučeniny toxicita MeSH
- buňky Hep G2 MeSH
- diacylglycerol-O-acyltransferasa genetika metabolismus MeSH
- diethylhexylftalát toxicita MeSH
- endokrinní disruptory * toxicita MeSH
- fenoly toxicita MeSH
- fluorokarbony toxicita MeSH
- kapryláty toxicita MeSH
- lidé MeSH
- metabolismus lipidů účinky léků MeSH
- sloučeniny bisfenolu A MeSH
- viabilita buněk účinky léků MeSH
- ztučnělá játra * chemicky indukované metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- benzhydrylové sloučeniny MeSH
- bisphenol A MeSH Prohlížeč
- DGAT1 protein, human MeSH Prohlížeč
- diacylglycerol-O-acyltransferasa MeSH
- diethylhexylftalát MeSH
- endokrinní disruptory * MeSH
- fenoly MeSH
- fluorokarbony MeSH
- kapryláty MeSH
- perfluorooctanoic acid MeSH Prohlížeč
- sloučeniny bisfenolu A MeSH
In recent decades, obesity and its associated health issues have risen dramatically. The COVID-19 pandemic has further exacerbated this trend, underscoring the pressing need for new strategies to manage weight. Functional foods designed to modulate lipid digestion and absorption rates and thereby reduce the assimilation of dietary fats have gained increasing attention in food science as a potentially safer alternative to weight-loss medications. This review provides insights into controlled lipid digestion and customized delivery of fats. The first section introduces basic concepts of lipid digestion and absorption in the human gastrointestinal tract. The second section discusses factors regulating lipid digestion and absorption rates, as well as strategies for modulating lipid assimilation from food. The third section focuses on applications of controlled lipid digestion in developing personalized foods designed for specific consumer groups, with particular emphasis on two target populations: overweight individuals and infants.
- Klíčová slova
- Controlled lipid digestion, Dietary fat, Food design, Functional foods, Infant formula, Obesity, Personalized nutrition, Weight loss,
- MeSH
- COVID-19 metabolismus prevence a kontrola MeSH
- dietní tuky * metabolismus MeSH
- funkční potraviny * analýza MeSH
- gastrointestinální trakt metabolismus MeSH
- lidé MeSH
- metabolismus lipidů MeSH
- obezita metabolismus dietoterapie patofyziologie MeSH
- trávení * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- dietní tuky * MeSH
