BACKGROUND & OBJECTIVE: To analyze whether there is an association between pre-pregnancy lipid parameters and gestational diabetes mellitus (GDM) in women undergoing assisted reproductive technologies (ART), a group especially at risk for GDM, and if so, which parameter is associated the strongest. METHODS: Data was collected at the Reproductive and Genetic Hospital CITIC-Xiangya in Changsha, China from January 2017 to December 2018. The measured lipid parameters include LDL (low-density lipoprotein), HDL (high-density lipoprotein), TC (total cholesterol), and TG (triglycerides). RESULTS: 119 (15.5%) of the 767 patients developed GDM. On average, women who developed GDM were older, had a higher BMI, LDL, TC, and TG, and lower HDL. After adjusting for confounders, LDL and HDL showed a significant association with GDM (p < 0.05), but TC and TG did not. Binary LDL/HDL and TC/HDL ratios showed the strongest association with GDM incidence (OR 1.957 [95%CI 1.258-3.044] and 1.942 [1.243-3.034] respectively). Subgroup analysis showed that an elevated LDL/HDL ratio also increased GDM risk in subgroups with a typically lower prevalence of GDM, such as young women with a low BMI and low blood pressure. Both lipid ratios (LDL/HDL and TC/HD) show strong interactions with baseline age, fasting plasma glucose, and LH. CONCLUSIONS: In this cohort of Chinese women undergoing ART, pre-pregnancy LDL/HDL and TC/HDL were associated with GDM the strongest from the lipid parameters and could be useful to estimate GDM risk even before ART treatments and pregnancy. CLINICAL TRIAL NUMBER: NCT03503006 registered on the 21st of March 2018 (on clinicaltrials.gov). https://clinicaltrials.gov/study/NCT03503006?locStr=Changsha,%20Hunan,%20China&country=China&state=Hunan&city=Changsha&cond=ivf&rank=2 .
- MeSH
- asistovaná reprodukce * MeSH
- cholesterol krev MeSH
- dospělí MeSH
- gestační diabetes * krev epidemiologie diagnóza MeSH
- HDL-cholesterol * krev MeSH
- LDL-cholesterol krev MeSH
- lidé MeSH
- rizikové faktory MeSH
- těhotenství MeSH
- triglyceridy krev MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
- Geografické názvy
- Čína MeSH
This study hypothesized that SCFA, acetate impacts positively on hypothalamic pyroptosis and its related abnormalities in experimentally induced PCOS rat model, possibly through NrF2/HIF1-α modulation. Eight-week-old female Wister rats were divided into groups (n = 5), namely control, PCOS, acetate and PCOS + acetate groups. Induction of PCOS was performed by administering 1 mg/kg body weight of letrozole for 21 days. After PCOS confirmation, the animals were treated with 200 mg/kg of acetate for 6 weeks. Rats with PCOS were characterized with insulin resistance, leptin resistance, increased plasma testosterone as well as degenerated ovarian follicles. There was also a significant increase in hypothalamic triglyceride level, triglyceride-glucose index, inflammatory biomarkers (SDF-1 and NF-kB) and caspase-6 as well as plasma LH and triglyceride. A decrease was observed in plasma adiponectin, GnRH, FSH, and hypothalamic GABA with severe inflammasome expression in PCOS rats. These were accompanied by decreased level of NrF2/HIF1-α, and the alterations were reversed when treated with acetate. Collectively, the present results suggest the therapeutic impact of acetate on hypothalamic pyroptosis and its related comorbidity in PCOS, a beneficial effect that is accompanied by modulation of NrF2/HIF1-α.
- MeSH
- adiponektin metabolismus krev MeSH
- faktor 1 indukovatelný hypoxií - podjednotka alfa * metabolismus MeSH
- faktor 2 související s NF-E2 metabolismus MeSH
- folikuly stimulující hormon krev MeSH
- GABA metabolismus MeSH
- hormon uvolňující gonadotropiny metabolismus MeSH
- hypothalamus * metabolismus účinky léků patologie MeSH
- inzulinová rezistence MeSH
- krysa rodu rattus MeSH
- leptin krev metabolismus MeSH
- letrozol farmakologie MeSH
- luteinizační hormon krev MeSH
- modely nemocí na zvířatech MeSH
- potkani Wistar * MeSH
- pyroptóza * účinky léků MeSH
- syndrom polycystických ovarií * chemicky indukované metabolismus farmakoterapie patologie MeSH
- testosteron krev MeSH
- triglyceridy krev metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Exposures to social and environmental stressors arise individual behavioural response and thus indirectly affect cardiometabolic health. The aim of this study was to investigate several social and environmental stressors and the paths of their influence on cardiometabolic health. The data of 2154 participants (aged 25-64 years) from the cross-sectional population-based study were analysed. The composite score of metabolic disorders (MS score) was calculated based on 5 biomarkers: waist circumference, blood pressure, fasting blood glucose, HDL-cholesterol, triglycerides. The effects of social stressors (education level, income), environmental stressors (NO2, noise) and behavioural factors (unhealthy diet, smoking, alcohol consumption, sedentary behaviours) on MS score were assessed using a structural model. We observed a direct effect of education on MS score, as well as an indirect effect mediated via an unhealthy diet, smoking, and sedentary behaviours. We also observed a significant indirect effect of income via sedentary behaviours. The only environmental stressor predicting MS was noise, which also mediated the effect of education. In summary, the effect of social stressors on the development of cardiometabolic risk had a higher magnitude than the effect of the assessed environmental factors. Social stressors lead to an individual's unhealthy behaviour and might predispose individuals to higher levels of environmental stressors exposures.
- MeSH
- biologické markery krev MeSH
- dospělí MeSH
- HDL-cholesterol krev MeSH
- kardiovaskulární nemoci etiologie epidemiologie MeSH
- kouření škodlivé účinky MeSH
- krevní glukóza metabolismus MeSH
- krevní tlak MeSH
- lidé středního věku MeSH
- lidé MeSH
- metabolické nemoci etiologie epidemiologie MeSH
- obvod pasu MeSH
- průřezové studie MeSH
- psychický stres MeSH
- rizikové faktory MeSH
- sedavý životní styl * MeSH
- triglyceridy krev MeSH
- vystavení vlivu životního prostředí škodlivé účinky MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Rozvoj možností ovlivnění koncentrací iipoproteinů krevní plazmy jde velmi rychle kupředu. Kromě zcela nových léčiv se rozšiřuje spektrum kombinací déie užívaných moiekui, stejně jako praktické možnosti preskripce a dostupnost léčiv, která v našich podmínkách nebyla k dispozici (iomitapid). Dostáváme k dispozici nová léčiva ovlivňující koncentrace LDL (iipoproteiny s nízkou hustotou, iow-density lipoproteins) cholesterolu (např. bempedoová kyselina, RNA terapeutika či monokionáiní protilátky - evinacumab), klinickým testováním procházejí malé molekuly (obicetrapib) i peroráině podávané inhibitory proprotein konvertázy subtiiisinu/kexinu typu 9 (proprotein convertase subtiiisin/kexin type 9, PCSK9). Koncentrace trigiyceridů budeme moci cíleně ovlivňovat léčivy s účinky na iipoiytické schopnosti iipoproteinové iipázy (inhibitory apoiipoproteinu CIII [apo-CIII] či angiopoetinu podobný protein 3 [angiopoietin-iike 3 protein, ANGPTL3]). Veiká pozornost je věnována novým možnostem ovlivnění koncentrací iipoproteinu (a) pomocí RNA terapeutik (antisense [protisměrné] oiigonukieotidy i maié interferující RNA fragmenty). Mimořádně zajímavý je rozvoj technik genové editace, který se v první fázi rovněž obrací k iipidovému metabolismu. Aktuálně probíhá první studie u pacientů s heterozygotní familiární hyperchoiesteroiemií, u nichž byia provedena jednorázová editace genu pro systémem editace genů segmenty nahromaděných pravidelně rozmístěných krátkých paiindromických repetic (clustered regularly interspaced palindromic repeats associated genes, CRISPR/Cas9) následovaná poklesem koncentrací LDL cholesterolu o 50 %.
The deveiopment of options for influencing biood piasma iipoprotein ieveis is progressing rapidiy. In addition to compieteiy new drugs, the spectrum of combinations of ionger used moiecuies is expanding, as weii as the practicai possibiiities of prescription and avaiiabiiity of drugs that were not avaiiabie in our conditions (iomitapide). New drugs affecting LDL (iow-density iipoproteins) choiesteroi ieveis are becoming avaiiabie (e.g., bempedoic acid, RNA therapeutics or monocionai antibodies - evinacumab), smaii moiecuies (obicetrapib) and new oraiiy administered PCSK9 (proprotein convertase subtiiisin/kexin type 9) inhibitors are undergoing ciinicai triais. We wiii be abie to target trigiyceride ieveis with drugs affecting the iipoiytic capacity of iipoprotein iipase (inhibitors of apoiipoprotein CIII [apo-CIII] or angiopoietin-iike 3 protein [ANGPTL3]). Much attention is paid to new possibiiities of influencing iipoprotein (a) concentrations by RNA therapeutics (antisense oiigonucieotides and smaii interfering RNA fragments). Of particuiar interest is the deveiopment of gene editing techniques, which in the first phase aiso turn to iipid metaboiism. Currentiy, the first study is underway in patients with heterozygous famiiiai hyperchoiesteroiemia, in whom a singie gene editing of the PCSK9 gene by the ciustered reguiariy interspaced paiindromic repeats associated genes (CRISPR/Cas9) system foiiowed by a 50% decrease in LDL-choiesteroi ieveis.
- Klíčová slova
- studie VERDE 101, kyselina bempedoová, inhibitory CETP,
- MeSH
- apolipoprotein C-III farmakologie MeSH
- dyslipidemie * farmakoterapie krev MeSH
- editace genu MeSH
- klinické zkoušky jako téma MeSH
- LDL-cholesterol farmakologie krev MeSH
- lidé MeSH
- monoklonální protilátky farmakologie terapeutické užití MeSH
- PCSK9 inhibitory farmakologie MeSH
- triglyceridy farmakologie krev MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
Fibroblast growth factor 21 (FGF21) reduces body weight, which was attributed to induced energy expenditure (EE). Conflicting data have been published on the role of uncoupling protein 1 (UCP1) in this effect. Therefore, we aimed to revisit the thermoregulatory effects of FGF21 and their implications for body weight regulation. We found that an 8-day treatment with FGF21 lowers body weight to similar extent in both wildtype (WT) and UCP1-deficient (KO) mice fed high-fat diet. In WT mice, this effect is solely due to increased EE, associated with a strong activation of UCP1 and with excess heat dissipated through the tail. This thermogenesis takes place in the interscapular region and can be attenuated by a β-adrenergic inhibitor propranolol. In KO mice, FGF21-induced weight loss correlates with a modest increase in EE, which is independent of adrenergic signaling, and with a reduced energy intake. Interestingly, the gene expression profile of interscapular brown adipose tissue (but not subcutaneous white adipose tissue) of KO mice is massively affected by FGF21, as shown by increased expression of genes encoding triacylglycerol/free fatty acid cycle enzymes. Thus, FGF21 elicits central thermogenic and pyretic effects followed by a concomitant increase in EE and body temperature, respectively. The associated weight loss is strongly dependent on UCP1-based thermogenesis. However, in the absence of UCP1, alternative mechanisms of energy dissipation may contribute, possibly based on futile triacylglycerol/free fatty acid cycling in brown adipose tissue and reduced food intake.
- MeSH
- adrenergní látky MeSH
- energetický metabolismus MeSH
- fibroblastové růstové faktory * MeSH
- hmotnostní úbytek * MeSH
- kyseliny mastné neesterifikované * MeSH
- myši obézní MeSH
- myši MeSH
- tělesná hmotnost MeSH
- triglyceridy MeSH
- uncoupling protein 1 genetika MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Nitrogen is one of the most important nutrient sources for the growth of microalgae. We studied the effects of nitrogen starvation on the growth responses, biochemical composition, and fatty acid profile of Dunaliella tertiolecta, Phaeodactylum tricornutum, and Nannochloropsis oculata. The lack of nitrogen caused changes in carbohydrate, protein, lipid, and fatty acid composition in all examined microalgae. The carbohydrate content increased 59% in D. tertiolecta, while the lipid level increased 139% in P. tricornutum under nitrogen stress conditions compared to the control groups. Nitrogen starvation increased the oligosaccharide and polysaccharide contents of D. tertiolecta 4.1-fold and 3.6-fold, respectively. Furthermore, triacylglycerol (TAG) levels in N. oculata and P. tricornutum increased 2.3-fold and 7.4-fold, respectively. The dramatic increase in the amount of TAG is important for the use of these microalgae as raw materials in biodiesel. Nitrogen starvation increased the amounts of oligosaccharides and polysaccharides of D. tertiolecta, while increased eicosapentaenoic acid (EPA) in N. oculata and docosahexaenoic acid (DHA) content in P. tricornutum. The amount of polyunsaturated fatty acids (PUFAs), EPA, DHA, oligosaccharides, and polysaccharides in microalgal species can be increased without using the too costly nitrogen source in the culture conditions, which can reduce the most costly of living feeding.
OBJECTIVE: This study tested the hypothesis that limited subcutaneous adipose tissue (SAT) expansion represents a primary predisposition to the development of type 2 diabetes mellitus (T2DM), independent of obesity, and identified novel markers of SAT dysfunction in the inheritance of T2DM. METHODS: First-degree relatives (FDR) of T2DM patients (n = 19) and control individuals (n = 19) without obesity (fat mass < 25%) were cross-sectionally compared. Body composition (bioimpedance, computed tomography) and insulin sensitivity (IS; oral glucose tolerance test, clamp) were measured. SAT obtained by needle biopsy was used to analyze adipocyte size, lipidome, mRNA expression, and inflammatory markers. Primary cultures of adipose precursors were analyzed for adipogenic capacity and metabolism. RESULTS: Compared with control individuals, FDR individuals had lower IS and a higher amount of visceral fat. However, SAT-derived adipose precursors did not differ in their ability to proliferate and differentiate or in metabolic parameters (lipolysis, mitochondrial oxidation). In SAT of FDR individuals, lipidomic and mRNA expression analysis revealed accumulation of triglycerides containing polyunsaturated fatty acids and increased mRNA expression of lysyl oxidase (LOX). These parameters correlated with IS, visceral fat accumulation, and mRNA expression of inflammatory and cellular stress genes. CONCLUSIONS: The intrinsic adipogenic potential of SAT is not affected by a family history of T2DM. However, alterations in LOX mRNA and polyunsaturated fatty acids in triacylglycerols are likely related to the risk of developing T2DM independent of obesity.
- MeSH
- diabetes mellitus 2. typu * genetika metabolismus MeSH
- inzulinová rezistence * genetika MeSH
- lidé MeSH
- messenger RNA metabolismus MeSH
- nenasycené mastné kyseliny metabolismus MeSH
- nitrobřišní tuk metabolismus MeSH
- obezita genetika metabolismus MeSH
- podkožní tuk metabolismus MeSH
- průřezové studie MeSH
- triglyceridy metabolismus MeSH
- tuková tkáň metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
This study investigated the therapeutic potential of probiotic bifidobacteria, isolated from Iranian fermented dairy products, in a hyperlipidemic animal model. Bifidobacterium strains were extracted from traditional dairy samples and screened using physiological and phenotypic examinations, 16S rRNA analysis, and probiotic properties such as tolerance to gastrointestinal juice, antimicrobial activity, and antibiotic susceptibility. The ability of the screened bifidobacteria to reduce serum and liver lipids in vivo was tested using male Wistar rats. Six strains of bifidobacteria were isolated from traditional Iranian fermented dairy. These strains showed promising in vitro activity in lowering triglyceride and cholesterol, tolerance to simulated gastrointestinal juice, the ability to adhere to Caco-2 cells, acceptable antibiotic susceptibility, and a broad spectrum of antibacterial activity. The diet supplemented with isolated bifidobacteria significantly reduced serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), liver tissue lipid levels, and hepatic enzymes in animals when compared to a high-fat diet without strains (p < 0.01). Additionally, the potential probiotic-supplemented diet significantly increased bile acid excretion in the feces and upregulated hepatic CYP7A1 expression levels (p < 0.05), while NPC1L1, ACAT2, and MTP gene expressions in small intestinal cells were downregulated (p < 0.05). Bifidobacteria isolated from Iranian traditional dairy showed potential for use in the production of fermented foods that have hypolipemic activity in the host.
- MeSH
- antibakteriální látky farmakologie MeSH
- Bifidobacterium * genetika izolace a purifikace metabolismus MeSH
- Caco-2 buňky MeSH
- cholesterol-7-alfa-hydroxylasa genetika metabolismus MeSH
- cholesterol krev metabolismus MeSH
- feces mikrobiologie MeSH
- hyperlipidemie * MeSH
- játra metabolismus MeSH
- krysa rodu rattus MeSH
- lidé MeSH
- mléčné výrobky mikrobiologie MeSH
- modely nemocí na zvířatech MeSH
- potkani Wistar * MeSH
- probiotika * aplikace a dávkování farmakologie MeSH
- RNA ribozomální 16S genetika MeSH
- triglyceridy krev metabolismus MeSH
- žlučové kyseliny a soli metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Írán MeSH
Although some clinical studies have reported increased mitochondrial respiration in patients with fatty liver and early non‐alcoholic steatohepatitis (NASH), there is a lack of in vitro models of non‐alcoholic fatty liver disease (NAFLD) with similar findings. Despite being the most commonly used immortalized cell line for in vitro models of NAFLD, HepG2 cells exposed to free fatty acids (FFAs) exhibit a decreased mitochondrial respiration. On the other hand, the use of HepaRG cells to study mitochondrial respiratory changes following exposure to FFAs has not yet been fully explored. Therefore, the present study aimed to assess cellular energy metabolism, particularly mitochondrial respiration, and lipotoxicity in FFA‐treated HepaRG and HepG2 cells. HepaRG and HepG2 cells were exposed to FFAs, followed by comparative analyses that examained cellular metabolism, mitochondrial respiratory enzyme activities, mitochondrial morphology, lipotoxicity, the mRNA expression of selected genes and triacylglycerol (TAG) accumulation. FFAs stimulated mitochondrial respiration and glycolysis in HepaRG cells, but not in HepG2 cells. Stimulated complex I, II‐driven respiration and β‐oxidation were linked to increased complex I and II activities in FFA‐treated HepaRG cells, but not in FFA‐treated HepG2 cells. Exposure to FFAs disrupted mitochondrial morphology in both HepaRG and HepG2 cells. Lipotoxicity was induced to a greater extent in FFA‐treated HepaRG cells than in FFA‐treated HepG2 cells. TAG accumulation was less prominent in HepaRG cells than in HepG2 cells. On the whole, the present study demonstrates that stimulated mitochondrial respiration is associated with lipotoxicity in FFA‐treated HepaRG cells, but not in FFA‐treated HepG2 cells. These findings suggest that HepaRG cells are more suitable for assessing mitochondrial respiratory adaptations in the developed in vitro model of early‐stage NASH.
- MeSH
- buněčné linie MeSH
- buňky Hep G2 MeSH
- dýchání MeSH
- kyseliny mastné neesterifikované MeSH
- lidé MeSH
- mitochondrie MeSH
- nealkoholová steatóza jater * MeSH
- triglyceridy MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
INTRODUCTION: Regular physical activity and dietary variety are modifiable and influential factors of health outcomes. However, the cumulative effects of these behaviors are not well understood. Metabolomics may have a promising research potential to extend our knowledge and use it in the attempts to find a long-term and sustainable personalized approach in exercise and diet recommendations. OBJECTIVE: The main aim was to investigate the effect of the 12 week very low carbohydrate high fat (VLCHF) diet and high-intensity interval training (HIIT) on lipidomic and metabolomic profiles in individuals with overweight and obesity. METHODS: The participants (N = 91) were randomly allocated to HIIT (N = 22), VLCHF (N = 25), VLCHF + HIIT (N = 25) or control (N = 19) groups for 12 weeks. Fasting plasma samples were collected before the intervention and after 4, 8 and 12 weeks. The samples were then subjected to untargeted lipidomic and metabolomic analyses using reversed phase ultra-high-performance liquid chromatography coupled to high-resolution mass spectrometry. RESULTS: The VLCHF diet affected plasma lipids considerably while the effect of HIIT was unremarkable. Already after 4 weeks of intervention substantial changes of plasma lipids were found in both VLCHF diet groups. The changes persisted throughout the entire 12 weeks of the VLCHF diet. Specifically, acyl carnitines, plasmalogens, fatty acyl esters of hydroxy fatty acid, sphingomyelin, ceramides, cholesterol esters, fatty acids and 4-hydroxybutyric were identified as lipid families that increased in the VLCHF diet groups whereas lipid families of triglycerides and glycerophospholipids decreased. Additionally, metabolomic analysis showed a decrease of theobromine. CONCLUSIONS: This study deciphers the specific responses to a VLCHF diet, HIIT and their combination by analysing untargeted lipidomic and metabolomic profile. VLCHF diet caused divergent changes of plasma lipids and other metabolites when compared to the exercise and control group which may contribute to a better understanding of metabolic changes and the appraisal of VLCHF diet benefits and harms. CLINICAL TRIAL REGISTRY NUMBER: NCT03934476, registered 1st May 2019 https://clinicaltrials.gov/ct2/show/NCT03934476?term=NCT03934476&draw=2&rank=1 .
