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
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
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 .
The pathogenesis of non-alcoholic fatty liver disease (NAFLD) is associated with abnormalities of liver lipid metabolism. On the contrary, a diet enriched with n-3 polyunsaturated fatty acids (n-3-PUFAs) has been reported to ameliorate the progression of NAFLD. The aim of our study was to investigate the impact of dietary n-3-PUFA enrichment on the development of NAFLD and liver lipidome. Mice were fed for 6 weeks either a high-fat methionine choline-deficient diet (MCD) or standard chow with or without n-3-PUFAs. Liver histology, serum biochemistry, detailed plasma and liver lipidomic analyses, and genome-wide transcriptome analysis were performed. Mice fed an MCD developed histopathological changes characteristic of NAFLD, and these changes were ameliorated with n-3-PUFAs. Simultaneously, n-3-PUFAs decreased serum triacylglycerol and cholesterol concentrations as well as ALT and AST activities. N-3-PUFAs decreased serum concentrations of saturated and monounsaturated free fatty acids (FAs), while increasing serum concentrations of long-chain PUFAs. Furthermore, in the liver, the MCD significantly increased the hepatic triacylglycerol content, while the administration of n-3-PUFAs eliminated this effect. Administration of n-3-PUFAs led to significant beneficial differences in gene expression within biosynthetic pathways of cholesterol, FAs, and pro-inflammatory cytokines (IL-1 and TNF-α). To conclude, n-3-PUFA supplementation appears to represent a promising nutraceutical approach for the restoration of abnormalities in liver lipid metabolism and the prevention and treatment of NAFLD.
- MeSH
- cholesterol metabolismus MeSH
- cholin metabolismus MeSH
- dieta s vysokým obsahem tuků škodlivé účinky MeSH
- játra metabolismus MeSH
- kyseliny mastné neesterifikované metabolismus MeSH
- kyseliny mastné omega-3 * farmakologie terapeutické užití metabolismus MeSH
- methionin metabolismus MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- nealkoholová steatóza jater * etiologie genetika MeSH
- nenasycené mastné kyseliny metabolismus MeSH
- Racemethionin metabolismus farmakologie MeSH
- triglyceridy metabolismus MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
PURPOSE OF REVIEW: This article sumarizes pathopysiological consequencies between obesity and dyslipidemia and aims to bring some practical approach. RECENT FINDINGS: Dyslipidemia is often present in individuals with obesity and simultaneusly, many obese individuals have lipid metabolism disorders. Especially the abdominal obesity increases the cardiometabolic risk because of the presence of atherogenic dyslipidemia while the total low density lipoprotein cholesterol (LDL-C) may be normal. LDL-C is the primary goal in dyslipidemia treatment. Apoliprotein B (Apo B) and non - high density lipoprotein cholesterol (non-HDL-C) should be estimated to precise the cardiovascular risk and represents the secondary goal in treatment. Weight loss either with diet or antiobestic medication induces the decrease in triglycerides (TG) and LDL-C and the increase in HDL-C. Composition of nutrients, esp. fatty acids, influences lipid levels. Bariatric surgery is efficient in weight loss and has a significant effect on serum lipids. Dyslipidemia and obesity present common diseases that must be managed to decrease the cardiovascular risk and the risk of obesity-related complications.
- MeSH
- dieta MeSH
- dyslipidemie * komplikace MeSH
- HDL-cholesterol MeSH
- hmotnostní úbytek MeSH
- LDL-cholesterol MeSH
- lidé MeSH
- lipoproteiny MeSH
- obezita * komplikace epidemiologie MeSH
- triglyceridy MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
OBJECTIVES: Roma population is one of the major ethnic groups in the Central and Eastern Europe, having high rates of chronic diseases and associated risk factors related to their poor social conditions, unhealthy lifestyle and low educational level. The purpose of our study was to assess the health status of Roma from South Bulgaria by means of blood indicators and determine the prevalence of some cardiovascular (CV) risk factors in the Roma population sample. METHODS: The study group consisted of 60 Roma (23 men and 37 women), mean age 53.7 ± 15.9 years, and the control group consisted of 68 non-Roma from the majority population (29 men and 38 women), mean age 45.8 ± 12.2 years. The data were collected via questionnaire, anthropometric measures, and venous blood samples analyses after an overnight fasting. RESULTS: The Roma population subjects were slightly but significantly older compared to the non-Roma group and both study groups included more women. The fasting glucose, body mass index (BMI), triglycerides (TG), total cholesterol (TC), and LDL-cholesterol (LDL-C) levels were significantly higher, and HDL-cholesterol (HDL-C) levels were significantly lower in Roma compared to the control non-Roma group. The values of cardiovascular risk markers such as TC/HDL-C and TG/HDL-C ratios, atherogenic index of plasma (AIP) and lipoprotein combine index (LCI) were significantly higher in Roma compared to non-Roma subjects. The prevalence of obesity in Roma was 35%, diabetes mellitus was recorded in 16.7% of the entire Roma sample, and hyperglycaemia in non-diabetics was recorded in 32%. Hypercholesterolaemia was found in 90% and hypertriglyceridaemia was found in 88.3%. The prevalence of cardiovascular diseases (CVD) was high and was encountered in 71.7% of the Roma participants and most of the subjects (96.7%) reported family history of CVD. The studied population showed high smoking rates with 33.3% active smokers. CONCLUSIONS: Our study confirmed high prevalence of CV risk factors among Roma population, such as abnormal lipid profile parameters, obesity and heavy smoking and very high cardiovascular morbidity rate. Therefore, adequate measures and healthcare programmes aiming at the early identification, treatment and prevention of CVD risks among Roma are necessary.
- MeSH
- dospělí MeSH
- HDL-cholesterol MeSH
- kardiovaskulární nemoci * epidemiologie prevence a kontrola MeSH
- lidé středního věku MeSH
- lidé MeSH
- obezita MeSH
- rizikové faktory kardiovaskulárních chorob MeSH
- rizikové faktory MeSH
- senioři MeSH
- triglyceridy MeSH
- zdravotní stav MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Bulharsko MeSH
This meta-analysis of randomized controlled trials (RCTs) was performed to summarize the effects of probiotics, prebiotics, and synbiotics on insulin resistance (IR), lipid profiles, anthropometric indices, and C-reactive protein (CRP) level for polycystic ovary syndrome (PCOS). We searched 8 databases from their inception until 1st October, 2020. The effect sizes were expressed as standardized mean difference (SMD) with 95% confidence intervals (95% CI). Subgroup analyses were undertaken for further identification of effects of probiotics, prebiotics, and synbiotics, based on the following aspects: (1) type of intervention (probiotics, prebiotics, or synbiotics); (2) study duration (≥ 12 weeks or < 12 weeks); (3) number of probiotic strains (multi strains or single strain); (4) probiotic dose (≥ 2 × 108 colony-forming units [CFU] or < 2 × 108 CFU). A total of 17 eligible RCTs with 1049 participants were included. Results showed that probiotic, prebiotic, and synbiotic intake decreased fasting plasma glucose (SMD, -1.35; 95% CI, -2.22 to -0.49; p = 0.002), fasting insulin (SMD, -0.68; 95% CI, -1.08 to -0.27; p = 0.001), homeostatic model of assessment for IR (SMD, -0.73; 95% CI, -1.15 to -0.31; p = 0.001), triglycerides (SMD, -0.85; 95% CI, -1.59 to -0.11; p = 0.024), total cholesterol (SMD, -1.09; 95% CI, -1.98 to -0.21; p = 0.015), low-density lipoprotein cholesterol (SMD, -0.84; 95% CI, -1.64 to -0.03; p = 0.041), very-low-density lipoprotein cholesterol (SMD, -0.44; 95% CI, -0.70 to -0.18; p = 0.001), and increased quantitative insulin sensitivity check index (SMD, 2.00; 95% CI, - 0.79 to 3.22; p = 0.001). However, probiotic, prebiotic, and synbiotic supplements did not affect anthropometric indices, high-density lipoprotein cholesterol, and CRP levels. Subgroup analysis showed that probiotic or prebiotic might be the optimal choice for ameliorating IR or lipid profiles, respectively. Additionally, the effect was positively related to courses and therapeutical dose. Overall, the meta-analysis demonstrates that probiotic, prebiotic, or synbiotic administration is an effective and safe intervention for modifying IR and lipid profiles.
- MeSH
- HDL-cholesterol MeSH
- inzulinová rezistence * MeSH
- lidé MeSH
- prebiotika MeSH
- probiotika * terapeutické užití MeSH
- synbiotika * MeSH
- syndrom polycystických ovarií * metabolismus MeSH
- triglyceridy MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- systematický přehled MeSH
Statistical data show that pain intensity in patients with low back pain is associated with a higher BMI, total serum cholesterol, and triacylglycerol levels. The objective of our study was to evaluate how these associations are dependent on the nature of the patient-doctor relationship. Eighty-nine patients hospitalized with chronic low-back pain (50 women, 39 men; average age: 64.5 ± 12.7 years) were assessed over a 3-year period. A serum lipid analysis was conducted (LDL-C, HDL-C, and total cholesterols) at admission in parallel with a subjective evaluation of pain intensity, which was assessed using a numeric rating scale. The participating physician assigned, based on their personal interaction with the patient, an attribute of affinity (positive, neutral, and negative) towards them. Current serum lipid levels and pain intensity were correlated relative to these attributes. Pain intensity did not differ between the groups assigned positive or negative attributes of affinity. In patients belonging to the "positive" group, pain intensity correlated positively with total cholesterol (p=0.01) and LDL cholesterol (p=0.007). No correlations were found in the "negative" group or when the patient-doctor relationship was ignored. We found a significant association between subjectively assessed low back pain intensity and serum levels of total and LDL cholesterol in patients with whom the physician had a positive affinity. A positive affinity with the patients having chronic pain and the patient's trust in their physicians may ultimately mean that the patient's statement about pain is more credible, which may retroactively affect the outcome of therapy.
- MeSH
- LDL-cholesterol MeSH
- lidé středního věku MeSH
- lidé MeSH
- lipidy * MeSH
- lumbalgie * MeSH
- senioři MeSH
- triglyceridy MeSH
- vztahy mezi lékařem a pacientem MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
