Fasting induces significant shifts in substrate utilization with signs of acute insulin resistance (IR), while obesity is associated with chronic IR. Nonetheless, both states substantially influence adipose tissue (AT) function. Therefore, in this interventional study (NCT04260542), we investigated if excessive adiposity in premenopausal women alters insulin sensitivity and AT metabolic and endocrine activity in response to a 60-h fast and a subsequent 48-h refeeding period. Using physiological methods, lipidomics, and AT explants, we showed that obesity partially modified AT endocrine activity and blunted the dynamics of AT insulin resistance in response to the fasting/refeeding challenge compared to that observed in lean women. AT adapted to its own excess by reducing lipolytic activity/free fatty acids (FFA) flux per mass. This adaptation persisted even after a 60-h fast, resulting in lower ketosis in women with obesity. This could be a protective mechanism that limits the lipotoxic effects of FFA; however, it may ultimately impede desirable weight loss induced by caloric restriction in women with obesity.

• Publikační typ
• časopisecké články MeSH

BACKGROUND: Sodium-glucose cotransporter 2 inhibitors (SGLT-2i) are glucose-lowering agents used for the treatment of type 2 diabetes mellitus, which also improve heart failure and decrease the risk of cardiovascular complications. Epicardial adipose tissue (EAT) dysfunction was suggested to contribute to the development of heart failure. We aimed to elucidate a possible role of changes in EAT metabolic and inflammatory profile in the beneficial cardioprotective effects of SGLT-2i in subjects with severe heart failure. METHODS: 26 subjects with severe heart failure, with reduced ejection fraction, treated with SGLT-2i versus 26 subjects without treatment, matched for age (54.0 ± 2.1 vs. 55.3 ± 2.1 years, n.s.), body mass index (27.8 ± 0.9 vs. 28.8 ± 1.0 kg/m2, n.s.) and left ventricular ejection fraction (20.7 ± 0.5 vs. 23.2 ± 1.7%, n.s.), who were scheduled for heart transplantation or mechanical support implantation, were included in the study. A complex metabolomic and gene expression analysis of EAT obtained during surgery was performed. RESULTS: SGLT-2i ameliorated inflammation, as evidenced by the improved gene expression profile of pro-inflammatory genes in adipose tissue and decreased infiltration of immune cells into EAT. Enrichment of ether lipids with oleic acid noted on metabolomic analysis suggests a reduced disposition to ferroptosis, potentially further contributing to decreased oxidative stress in EAT of SGLT-2i treated subjects. CONCLUSIONS: Our results show decreased inflammation in EAT of patients with severe heart failure treated by SGLT-2i, as compared to patients with heart failure without this therapy. Modulation of EAT inflammatory and metabolic status could represent a novel mechanism behind SGLT-2i-associated cardioprotective effects in patients with heart failure.

• Klíčová slova
• Adipose tissue, Ether lipids, Heart failure, Inflammation, Sodium-glucose cotransporter 2 inhibitors,
• MeSH
• antiflogistika terapeutické užití   farmakologie   MeSH
• biologické markery krev   MeSH
• diabetes mellitus 2. typu farmakoterapie   metabolismus   diagnóza   MeSH
• epikardiální adipózní tkáň MeSH
• funkce levé komory srdeční účinky léků   MeSH
• glifloziny * terapeutické užití   farmakologie   škodlivé účinky   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mediátory zánětu * metabolismus   MeSH
• metabolomika MeSH
• perikard * metabolismus   účinky léků   MeSH
• srdeční selhání * metabolismus   patofyziologie   farmakoterapie   MeSH
• stupeň závažnosti nemoci * MeSH
• tepový objem účinky léků   MeSH
• tuková tkáň * účinky léků   metabolismus   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antiflogistika MeSH
• biologické markery MeSH
• glifloziny * MeSH
• mediátory zánětu * MeSH

Fatty acid esters of hydroxy fatty acids (FAHFAs) are endogenous bioactive lipids known for their anti-inflammatory and anti-diabetic properties. Despite their therapeutic potential, little is known about the sex-specific variations in FAHFA metabolism. This study investigated the role of Androgen Dependent TFPI Regulating Protein (ADTRP), a FAHFA hydrolase. Additionally, tissue-specific differences in FAHFA levels, focusing on the perigonadal white adipose tissue (pgWAT), subcutaneous white adipose tissue (scWAT), brown adipose tissue (BAT), plasma, and liver, were evaluated using metabolomics and lipidomics. We found that female mice exhibited higher FAHFA levels in pgWAT, scWAT, and BAT compared to males. FAHFA levels were inversely related to Adtrp mRNA, which showed significantly lower expression in females compared with males in pgWAT and scWAT. However, no significant differences between the sexes were observed in plasma and liver FAHFA levels. Adtrp deletion had minimal impact on both sexes' metabolome and lipidome of pgWAT. However, we discovered higher endogenous levels of triacylglycerol estolides containing FAHFAs, a FAHFA metabolic reservoir, in the pgWAT of female mice. These findings suggest that sex-dependent differences in FAHFA levels occur primarily in specific WAT depots and may modulate local insulin sensitivity in adipocytes. However, further investigations are warranted to fully comprehend the underlying mechanisms and implications of sex effects on FAHFA metabolism in humans.

• Klíčová slova
• Adtrp, FAHFA, adipose tissue, female, lipokines, male,
• Publikační typ
• časopisecké články MeSH
• preprinty MeSH

Triacylglycerol estolides (TG-EST) are biologically active lipids extensively studied for their anti-inflammatory and anti-diabetic properties. In this work, eight standards of TG-EST were synthesized and systematically investigated by nanoelectrospray tandem mass spectrometry. Mass spectra of synthetic TG-EST were studied with the purpose of enabling the unambiguous identification of these lipids in biological samples. TG-EST glycerol sn-regioisomers and isomers with the fatty acid ester of hydroxy fatty acid (FAHFA) subunit branched in the ω-, α-, or 10-position were used. Ammonium, lithium, and sodium adducts of TG-EST formed by nanoelectrospray ionization were subjected to collision-induced dissociation (CID) and higher-energy collisional dissociation (HCD). Product ion spectra allowed for identification of fatty acid (FA) and FAHFA subunits originally linked to the glycerol backbone and distinguished the α-branching site of the FAHFA from other estolide-branching isomers. The ω- and 10-branching sites were determined by combining CID with ozone-induced dissociation (OzID). Lithium adducts provided the most informative product ions, enabling characterization of FA, hydroxy fatty acid (HFA), and FAHFA subunits. Glycerol sn-regioisomers were distinguished based on the relative abundance of product ions and unambiguously identified using CID/OzID of lithium and sodium adducts.

• Klíčová slova
• collision-induced dissociation, estolide-branching isomers, glycerol sn-regioisomers, high-resolution mass spectrometry, higher-energy collisional dissociation, ozone-induced dissociation, triacylglycerol estolides,
• MeSH
• glycerol MeSH
• ionty MeSH
• lithium chemie   MeSH
• mastné kyseliny chemie   MeSH
• ozon * chemie   MeSH
• sodík MeSH
• tandemová hmotnostní spektrometrie * metody   MeSH
• triglyceridy chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• glycerol MeSH
• ionty MeSH
• lithium MeSH
• mastné kyseliny MeSH
• ozon * MeSH
• sodík MeSH
• triglyceridy MeSH

The aim of this study was to investigate the possible beneficial effects of exercise training (ET) with omega-3/Calanus oil supplementation on cardiorespiratory and adiposity parameters in elderly women. Fifty-five women (BMI: 19-37 kg/m2, 62-80 years old) were recruited and randomly assigned to the 4 month intervention with ET and omega-3 supplementation (Calanus oil, ET-Calanus) or ET and the placebo (sunflower oil; ET-Placebo). The body composition was determined by dual-energy X-ray absorptiometry (DXA), and cardiorespiratory parameters were measured using spiroergometry and PhysioFlow hemodynamic testing. Both interventions resulted in an increased lean mass whereas the fat mass was reduced in the leg and trunk as well as the android and gynoid regions. The content of trunk fat (in percent of the total fat) was lower and the content of the leg fat was higher in the ET-Calanus group compared with the ET-Placebo. Although both interventions resulted in similar improvements in cardiorespiratory fitness (VO2max), it was explained by an increased peripheral oxygen extraction (a-vO2diff) alone in the ET-Placebo group whereas increased values of both a-vO2diff and maximal cardiac output (COmax) were observed in the ET-Calanus group. Changes in COmax were associated with changes in systemic vascular resistance, circulating free fatty acids, and the omega-3 index. In conclusion, Calanus oil supplementation during a 4 month ET intervention in elderly women improved the cardiorespiratory function, which was due to combined central and peripheral cardiodynamic mechanisms.

• Klíčová slova
• aging, body composition, cardiac output, cardiorespiratory fitness, omega-3 fatty acids,
• MeSH
• cévní rezistence MeSH
• cvičení fyziologie   MeSH
• kardiorespirační zdatnost fyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• minutový srdeční výdej MeSH
• omega-3 mastné kyseliny aplikace a dávkování   MeSH
• plankton chemie   MeSH
• potravní doplňky * MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• složení těla MeSH
• stárnutí fyziologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• omega-3 mastné kyseliny MeSH

Later stages of secondary lymphedema are associated with the massive deposition of adipose tissue (AT). The factors driving lymphedema-associated AT (LAT) expansion in humans remain rather elusive. We hypothesized that LAT expansion could be based on alterations of metabolic, adipogenic, immune and/or angiogenic qualities of AT. AT samples were acquired from upper limbs of 11 women with unilateral breast cancer-related lymphedema and 11 healthy women without lymphedema. Additional control group of 11 female breast cancer survivors without lymphedema was used to assess systemic effects of lymphedema. AT was analysed for adipocyte size, lipolysis, angiogenesis, secretion of cytokines, immune and stem cell content and mRNA gene expression. Further, adipose precursors were isolated and tested for their proliferative and adipogenic capacity. The effect of undrained LAT- derived fluid on adipogenesis was also examined. Lymphedema did not have apparent systemic effect on metabolism and cytokine levels, but it was linked with higher lymphocyte numbers and altered levels of several miRNAs in blood. LAT showed higher basal lipolysis, (lymph)angiogenic capacity and secretion of inflammatory cytokines when compared to healthy AT. LAT contained more activated CD4+ T lymphocytes than healthy AT. mRNA levels of (lymph)angiogenic markers were deregulated in LAT and correlated with markers of lipolysis. In vitro, adipose cells derived from LAT did not differ in their proliferative, adipogenic, lipogenic and lipolytic potential from cells derived from healthy AT. Nevertheless, exposition of preadipocytes to LAT-derived fluid improved their adipogenic conversion when compared with the effect of serum. This study presents results of first complex analysis of LAT from upper limb of breast cancer survivors. Identified LAT alterations indicate a possible link between (lymph)angiogenesis and lipolysis. In addition, our in vitro results imply that AT expansion in lymphedema could be driven partially by exposition of adipose precursors to undrained LAT-derived fluid.

• MeSH
• cytokiny genetika   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• lipolýza MeSH
• lymfedém související s rakovinou prsu genetika   metabolismus   MeSH
• lymfedém genetika   metabolismus   MeSH
• přežívající onkologičtí pacienti MeSH
• regulace genové exprese MeSH
• senioři MeSH
• stanovení celkové genové exprese metody   MeSH
• studie případů a kontrol MeSH
• tuková tkáň metabolismus   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• cytokiny MeSH

Preclinical evidence suggests that n-3 fatty acids EPA and DHA (Omega-3) supplemented as phospholipids (PLs) may be more effective than triacylglycerols (TAGs) in reducing hepatic steatosis. To further test the ability of Omega-3 PLs to alleviate liver steatosis, we used a model of exacerbated non-alcoholic fatty liver disease based on high-fat feeding at thermoneutral temperature. Male C57BL/6N mice were fed for 24 weeks a lard-based diet given either alone (LHF) or supplemented with Omega-3 (30 mg/g diet) as PLs (krill oil; ω3PL) or TAGs (Epax 3000TG concentrate; ω3TG), which had a similar total content of EPA and DHA and their ratio. Substantial levels of TAG accumulation (~250 mg/g) but relatively low inflammation/fibrosis levels were achieved in the livers of control LHF mice. Liver steatosis was reduced by >40% in the ω3PL but not ω3TG group, and plasma ALT levels were markedly reduced (by 68%) in ω3PL mice as well. Krill oil administration also improved hepatic insulin sensitivity, and its effects were associated with high plasma adiponectin levels (150% of LHF mice) along with superior bioavailability of EPA, increased content of alkaloids stachydrine and trigonelline, suppression of lipogenic gene expression, and decreased diacylglycerol levels in the liver. This study reveals that in addition to Omega-3 PLs, other constituents of krill oil, such as alkaloids, may contribute to its strong antisteatotic effects in the liver.

• Klíčová slova
• C57BL/6N mice, NAFLD, high-fat diet, krill oil, obesity, omega-3, phospholipids, thermoneutral temperature,
• MeSH
• bydlení zvířat MeSH
• dieta s vysokým obsahem tuků škodlivé účinky   MeSH
• Euphausiacea MeSH
• fosfolipidy farmakologie   MeSH
• fyziologie výživy zvířat MeSH
• inzulinová rezistence MeSH
• játra metabolismus   MeSH
• modely nemocí na zvířatech MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• nealkoholová steatóza jater etiologie   terapie   MeSH
• obezita etiologie   terapie   MeSH
• potravní doplňky * MeSH
• rybí oleje farmakologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• fosfolipidy MeSH
• rybí oleje MeSH

Branched esters of palmitic acid and hydroxy stearic acid are antiinflammatory and antidiabetic lipokines that belong to a family of fatty acid (FA) esters of hydroxy fatty acids (HFAs) called FAHFAs. FAHFAs themselves belong to oligomeric FA esters, known as estolides. Glycerol-bound FAHFAs in triacylglycerols (TAGs), named TAG estolides, serve as metabolite reservoir of FAHFAs mobilized by lipases upon demand. Here, we characterized the involvement of two major metabolic lipases, adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL), in TAG estolide and FAHFA degradation. We synthesized a library of 20 TAG estolide isomers with FAHFAs varying in branching position, chain length, saturation grade, and position on the glycerol backbone and developed an in silico mass spectra library of all predicted catabolic intermediates. We found that ATGL alone or coactivated by comparative gene identification-58 efficiently liberated FAHFAs from TAG estolides with a preference for more compact substrates where the estolide branching point is located near the glycerol ester bond. ATGL was further involved in transesterification and remodeling reactions leading to the formation of TAG estolides with alternative acyl compositions. HSL represented a much more potent estolide bond hydrolase for both TAG estolides and free FAHFAs. FAHFA and TAG estolide accumulation in white adipose tissue of mice lacking HSL argued for a functional role of HSL in estolide catabolism in vivo. Our data show that ATGL and HSL participate in the metabolism of estolides and TAG estolides in distinct manners and are likely to affect the lipokine function of FAHFAs.

• Klíčová slova
• ATGL, FAHFA, HSL, lipokine,
• MeSH
• bílá tuková tkáň metabolismus   MeSH
• estery chemie   MeSH
• HEK293 buňky MeSH
• kyselina palmitová metabolismus   MeSH
• kyseliny stearové metabolismus   MeSH
• lidé MeSH
• lipasa metabolismus   MeSH
• lipolýza fyziologie   MeSH
• mastné kyseliny metabolismus   MeSH
• metabolismus fyziologie   MeSH
• myši knockoutované MeSH
• myši MeSH
• sterolesterasa metabolismus   MeSH
• triglyceridy metabolismus   MeSH
• tuková tkáň metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• estery MeSH
• kyselina palmitová MeSH
• kyseliny stearové MeSH
• lipasa MeSH
• mastné kyseliny MeSH
• stearic acid MeSH Prohlížeč
• sterolesterasa MeSH
• triglyceridy MeSH

We investigated changes in functional fitness after an exercise program in combination with Calanus oil supplementation, a novel source of bioactive lipids rich in wax esters with omega-3 polyunsaturated fatty acid (n-3 PUFA). Fifty-five healthy sedentary women aged 65-80 (mean age 70.9 ± 3.9 years, BMI 27.24 ± 3.9 kg m-2, VO2peak 19.46 ± 3.7 ml kg-1 min-1) were enrolled in the study. The participants were divided into two groups: exercise training plus Calanus Oil supplementation (n = 28) or exercise plus placebo (sunflower oil) supplementation (n = 27). The exercise intervention program was completed by 53 participants and contained functional circuit training (twice a week, 45 min plus 15 min of stretching and balance training) and Nordic walking (once a week, 60 min) for 16 weeks. Senior fitness test, exercise stress test on bicycle ergometer, hand-grip, and body composition were evaluated before and after the program. Our results show that functional fitness and body composition improved following the interventional exercise program, but for most of the parameters there was no synergic effect of supplementing n-3 PUFA-rich Calanus oil. In comparison to the placebo group, the group with Calanus supplementation experienced significantly higher improvement of functional strength of lower body which was evaluated by the chair stand test. Supplementation with Calanus may have a synergic effect with exercise on functional strength of the lower body in the elderly.

• Klíčová slova
• calanus oil, circuit training, nordic walking, older age,
• MeSH
• časové faktory MeSH
• Copepoda chemie   MeSH
• cvičení fyziologie   MeSH
• dietní tuky nenasycené aplikace a dávkování   izolace a purifikace   MeSH
• kondiční příprava metody   fyziologie   MeSH
• lidé MeSH
• omega-3 mastné kyseliny MeSH
• potravní doplňky * MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• síla ruky MeSH
• svalová síla MeSH
• tělesná výkonnost * MeSH
• věkové faktory MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• dietní tuky nenasycené MeSH
• omega-3 mastné kyseliny MeSH