Metabolic dysfunction-associated steatotic liver disease (MASLD) occurs in subjects with obesity and metabolic syndrome. MASLD may progress from simple steatosis (i.e., hepatic steatosis) to steatohepatitis, characterized by inflammatory changes and liver cell damage, substantially increasing mortality. Lifestyle measures associated with weight loss and/or appropriate diet help reduce liver fat accumulation, thereby potentially limiting progression to steatohepatitis. As for diet, both total energy and macronutrient composition significantly influence the liver's fat content. For example, the type of dietary fatty acids can affect the metabolism of lipids and hence their tissue accumulation, with saturated fatty acids having a greater ability to promote fat storage in the liver than polyunsaturated ones. In particular, polyunsaturated fatty acids of n-3 series (omega-3), such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), have been intensively studied for their antisteatotic effects, both in preclinical animal models of obesity and hepatic steatosis and in overweight/obese patients. Their effects may depend not only on the dose and duration of administration of omega-3, or DHA/EPA ratio, but also on the lipid class used for their supplementation. This review summarizes the available evidence from recent comparative studies using omega-3 supplementation via different lipid classes. Albeit the evidence is mainly limited to preclinical studies, it suggests that phospholipids and possibly wax esters could provide greater efficacy against MASLD compared to traditional chemical forms of omega-3 supplementation (i.e., triacylglycerols, ethyl esters). This cannot be attributed solely to improved EPA and/or DHA bioavailability, but other mechanisms may be involved. Keywords: MASLD • Metabolic dysfunction-associated steatotic liver disease • NAFLD • Non-alcoholic fatty liver disease • n-3 polyunsaturated fatty acids.

• MeSH
• játra * metabolismus   účinky léků   patologie   MeSH
• lidé MeSH
• metabolismus lipidů účinky léků   MeSH
• nealkoholová steatóza jater metabolismus   farmakoterapie   dietoterapie   patologie   MeSH
• obezita metabolismus   farmakoterapie   dietoterapie   patologie   MeSH
• omega-3 mastné kyseliny * aplikace a dávkování   metabolismus   terapeutické užití   MeSH
• potravní doplňky * MeSH
• ztučnělá játra metabolismus   farmakoterapie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• omega-3 mastné kyseliny * 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

Antisteatotic effects of omega-3 fatty acids (Omega-3) in obese rodents seem to vary depending on the lipid form of their administration. Whether these effects could reflect changes in intestinal metabolism is unknown. Here, we compare Omega-3-containing phospholipids (krill oil; ω3PL-H) and triacylglycerols (ω3TG) in terms of their effects on morphology, gene expression and fatty acid (FA) oxidation in the small intestine. Male C57BL/6N mice were fed for 8 weeks with a high-fat diet (HFD) alone or supplemented with 30 mg/g diet of ω3TG or ω3PL-H. Omega-3 index, reflecting the bioavailability of Omega-3, reached 12.5% and 7.5% in the ω3PL-H and ω3TG groups, respectively. Compared to HFD mice, ω3PL-H but not ω3TG animals had lower body weight gain (-40%), mesenteric adipose tissue (-43%), and hepatic lipid content (-64%). The highest number and expression level of regulated intestinal genes was observed in ω3PL-H mice. The expression of FA ω-oxidation genes was enhanced in both Omega-3-supplemented groups, but gene expression within the FA β-oxidation pathway and functional palmitate oxidation in the proximal ileum was significantly increased only in ω3PL-H mice. In conclusion, enhanced intestinal FA oxidation could contribute to the strong antisteatotic effects of Omega-3 when administered as phospholipids to dietary obese mice.

• Klíčová slova
• Omega-3 index, Omega-3 phospholipids, high-fat diet, krill oil, small intestine,
• MeSH
• dieta s vysokým obsahem tuků * MeSH
• erytrocytární membrána metabolismus   MeSH
• Euphausiacea MeSH
• fosfolipidy aplikace a dávkování   MeSH
• krevní glukóza analýza   MeSH
• mastné kyseliny metabolismus   MeSH
• metabolismus lipidů účinky léků   MeSH
• myši obézní MeSH
• oleje MeSH
• omega-3 mastné kyseliny aplikace a dávkování   MeSH
• oxidace-redukce MeSH
• střeva anatomie a histologie   MeSH
• střevní sliznice metabolismus   MeSH
• tělesná hmotnost MeSH
• triglyceridy aplikace a dávkování   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• fosfolipidy MeSH
• krevní glukóza MeSH
• mastné kyseliny MeSH
• oleje MeSH
• omega-3 mastné kyseliny MeSH
• triglyceridy MeSH

BACKGROUND/OBJECTIVE: Adaptation to the extrauterine environment depends on a switch from glycolysis to catabolism of fatty acids (FA) provided as milk lipids. We sought to learn whether the postnatal induction of muscle FA oxidation in mice could reflect propensity to obesity and to characterize the mechanisms controlling this induction. METHODS: Experiments were conducted using obesity-resistant A/J and obesity-prone C57BL/6J (B6) mice maintained at 30 °C, from 5 to 28 days after birth. At day 10, both A/J and B6 mice with genetic ablation (KO) of α2 subunit of AMP-activated protein kinase (AMPK) were also used. In skeletal muscle, expression of selected genes was determined using quantitative real-time PCR, and AMPK subunits content was evaluated using Western blotting. Activities of both AMPK and pyruvate dehydrogenase (PDH), as well as acylcarnitine levels in the muscle were measured. RESULTS: Acylcarnitine levels and gene expression indicated transient increase in FA oxidation during the first 2 weeks after birth, with a stronger increase in A/J mice. These data correlated with (i) the surge in plasma leptin levels, which peaked at day 10 and was higher in A/J mice, and (ii) relatively low activity of PDH linked with up-regulation of PDH kinase 4 gene (Pdk4) expression in the 10-day-old A/J mice. In contrast with the Pdk4 expression, transient up-regulation of uncoupling protein 3 gene was observed in B6 but not A/J mice. AMPK activity changed during the development, without major differences between A/J and B6 mice. Expression of neither Pdk4 nor other muscle genes was affected by AMPK-KO. CONCLUSIONS: Our results indicate a relatively strong postnatal induction of FA oxidation in skeletal muscle of the obesity-resistant A/J mice. This induction is transient and probably results from suppression of PDH activity, linked with a postnatal surge in plasma leptin levels, independent of AMPK.

• MeSH
• kosterní svaly metabolismus   MeSH
• mastné kyseliny metabolismus   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• novorozená zvířata MeSH
• obezita metabolismus   MeSH
• oxidace-redukce MeSH
• proteinkinasy aktivované AMP * genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• mastné kyseliny MeSH
• Prkaa2 protein, mouse MeSH Prohlížeč
• proteinkinasy aktivované AMP * MeSH

Metformin is currently the most prescribed drug for treatment of type 2 diabetes mellitus in humans. It has been well established that long-term treatment with metformin improves glucose tolerance in mice by inhibiting hepatic gluconeogenesis. Interestingly, a single dose of orally administered metformin acutely lowers blood glucose levels, however, little is known about the mechanism involved in this effect. Glucose tolerance, as assessed by the glucose tolerance test, was improved in response to prior oral metformin administration when compared to vehicle-treated mice, irrespective of whether the animals were fed either the standard or high-fat diet. Blood glucose-lowering effects of acutely administered metformin were also observed in mice lacking functional AMP-activated protein kinase, and were independent of glucagon-like-peptide-1 or N-methyl-D-aspartate receptors signaling. [18F]-FDG/PET revealed a slower intestinal transit of labeled glucose after metformin as compared to vehicle administration. Finally, metformin in a dose-dependent but indirect manner decreased glucose transport from the intestinal lumen into the blood, which was observed ex vivo as well as in vivo. Our results support the view that the inhibition of transepithelial glucose transport in the intestine is responsible for lowering blood glucose levels during an early response to oral administration of metformin.

• MeSH
• biologický transport účinky léků   MeSH
• diabetes mellitus 2. typu farmakoterapie   metabolismus   MeSH
• glukosa metabolismus   MeSH
• glukózový toleranční test MeSH
• hypoglykemika farmakologie   terapeutické užití   MeSH
• krevní glukóza metabolismus   MeSH
• lidé MeSH
• metformin farmakologie   terapeutické užití   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• proteinkinasy aktivované AMP metabolismus   MeSH
• střevní sliznice účinky léků   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• glukosa MeSH
• hypoglykemika MeSH
• krevní glukóza MeSH
• metformin MeSH
• proteinkinasy aktivované AMP MeSH

Cachexia represents a fatal energy-wasting syndrome in a large number of patients with cancer that mostly results in a pathological loss of skeletal muscle and adipose tissue. Here we show that tumor cell exposure and tumor growth in mice triggered a futile energy-wasting cycle in cultured white adipocytes and white adipose tissue (WAT), respectively. Although uncoupling protein 1 (Ucp1)-dependent thermogenesis was dispensable for tumor-induced body wasting, WAT from cachectic mice and tumor-cell-supernatant-treated adipocytes were consistently characterized by the simultaneous induction of both lipolytic and lipogenic pathways. Paradoxically, this was accompanied by an inactivated AMP-activated protein kinase (Ampk), which is normally activated in peripheral tissues during states of low cellular energy. Ampk inactivation correlated with its degradation and with upregulation of the Ampk-interacting protein Cidea. Therefore, we developed an Ampk-stabilizing peptide, ACIP, which was able to ameliorate WAT wasting in vitro and in vivo by shielding the Cidea-targeted interaction surface on Ampk. Thus, our data establish the Ucp1-independent remodeling of adipocyte lipid homeostasis as a key event in tumor-induced WAT wasting, and we propose the ACIP-dependent preservation of Ampk integrity in the WAT as a concept in future therapies for cachexia.

• MeSH
• bílá tuková tkáň účinky léků   metabolismus   MeSH
• bílé tukové buňky účinky léků   metabolismus   MeSH
• kachexie etiologie   metabolismus   MeSH
• kultivované buňky MeSH
• lipogeneze účinky léků   MeSH
• lipolýza účinky léků   MeSH
• metabolismus lipidů účinky léků   MeSH
• myši MeSH
• nádory komplikace   metabolismus   MeSH
• peptidové fragmenty farmakologie   MeSH
• proteinkinasy aktivované AMP metabolismus   farmakologie   MeSH
• proteiny regulující apoptózu účinky léků   metabolismus   MeSH
• techniky in vitro MeSH
• termogeneze účinky léků   MeSH
• uncoupling protein 1 účinky léků   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• Cidea protein, mouse MeSH Prohlížeč
• peptidové fragmenty MeSH
• Prkab1 protein, mouse MeSH Prohlížeč
• proteinkinasy aktivované AMP MeSH
• proteiny regulující apoptózu MeSH
• Ucp1 protein, mouse MeSH Prohlížeč
• uncoupling protein 1 MeSH

Obesity is associated with insulin resistance and impaired glucose tolerance, which represent characteristic features of the metabolic syndrome. Development of obesity is also linked to changes in fatty acid and amino acid metabolism observed in animal models of obesity as well as in humans. The aim of this study was to explore whether plasma metabolome, namely the levels of various acylcarnitines and amino acids, could serve as a biomarker of propensity to obesity and impaired glucose metabolism. Taking advantage of a high phenotypic variation in diet-induced obesity in C57BL/6J mice, 12-week-old male and female mice (n = 155) were fed a high-fat diet (lipids ~32 wt%) for a period of 10 weeks, while body weight gain (BWG) and changes in insulin sensitivity (ΔHOMA-IR) were assessed. Plasma samples were collected before (week 4) and after (week 22) high-fat feeding. Both univariate and multivariate statistical analyses were then used to examine the relationships between plasma metabolome and selected phenotypes including BWG and ΔHOMA-IR. Partial least squares-discrimination analysis was able to distinguish between animals selected either for their low or high BWG (or ΔHOMA-IR) in male but not female mice. Among the metabolites that differentiated male mice with low and high BWG, and which also belonged to the major discriminating metabolites when analyzed in plasma collected before and after high-fat feeding, were amino acids Tyr and Orn, as well as acylcarnitines C16-DC and C18:1-OH. In general, the separation of groups selected for their low or high ΔHOMA-IR was less evident and the outcomes of a corresponding multivariate analysis were much weaker than in case of BWG. Thus, our results document that plasma acylcarnitines and amino acids could serve as a gender-specific complex biomarker of propensity to obesity, however with a limited predictive value in case of the associated impairment of insulin sensitivity.

• MeSH
• aminokyseliny krev   MeSH
• analýza rozptylu MeSH
• biologické markery MeSH
• dieta s vysokým obsahem tuků škodlivé účinky   MeSH
• fenotyp MeSH
• glukózový toleranční test MeSH
• inzulinová rezistence MeSH
• karnitin analogy a deriváty   krev   MeSH
• krevní glukóza MeSH
• metabolom MeSH
• metabolomika metody   MeSH
• modely nemocí na zvířatech MeSH
• myši MeSH
• obezita krev   diagnóza   etiologie   MeSH
• porucha glukózové tolerance MeSH
• prognóza MeSH
• shluková analýza MeSH
• tendenční skóre MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• acylcarnitine MeSH Prohlížeč
• aminokyseliny MeSH
• biologické markery MeSH
• karnitin MeSH
• krevní glukóza MeSH

Insulin resistance, the key defect in type 2 diabetes (T2D), is associated with a low capacity to adapt fuel oxidation to fuel availability, i.e., metabolic inflexibility. This, in turn, contributes to a further damage of insulin signaling. Effectiveness of T2D treatment depends in large part on the improvement of insulin sensitivity and metabolic adaptability of the muscle, the main site of whole-body glucose utilization. We have shown previously in mice fed an obesogenic high-fat diet that a combined use of n-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFA) and thiazolidinediones (TZDs), anti-diabetic drugs, preserved metabolic health and synergistically improved muscle insulin sensitivity. We investigated here whether n-3 LC-PUFA could elicit additive beneficial effects on metabolic flexibility when combined with a TZD drug rosiglitazone. Adult male C57BL/6N mice were fed an obesogenic corn oil-based high-fat diet (cHF) for 8 weeks, or randomly assigned to various interventions: cHF with n-3 LC-PUFA concentrate replacing 15% of dietary lipids (cHF+F), cHF with 10 mg rosiglitazone/kg diet (cHF+ROSI), cHF+F+ROSI, or chow-fed. Indirect calorimetry demonstrated superior preservation of metabolic flexibility to carbohydrates in response to the combined intervention. Metabolomic and gene expression analyses in the muscle suggested distinct and complementary effects of the interventions, with n-3 LC-PUFA supporting complete oxidation of fatty acids in mitochondria and the combination with n-3 LC-PUFA and rosiglitazone augmenting insulin sensitivity by the modulation of branched-chain amino acid metabolism. These beneficial metabolic effects were associated with the activation of the switch between glycolytic and oxidative muscle fibers, especially in the cHF+F+ROSI mice. Our results further support the idea that the combined use of n-3 LC-PUFA and TZDs could improve the efficacy of the therapy of obese and diabetic patients.

• MeSH
• dieta s vysokým obsahem tuků škodlivé účinky   MeSH
• glykolýza účinky léků   MeSH
• kosterní svalová vlákna účinky léků   metabolismus   MeSH
• kosterní svaly účinky léků   metabolismus   MeSH
• metabolomika MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• obezita etiologie   metabolismus   MeSH
• omega-3 mastné kyseliny farmakologie   MeSH
• oxidace-redukce účinky léků   MeSH
• regulace genové exprese účinky léků   MeSH
• rosiglitazon MeSH
• synergismus léků MeSH
• thiazolidindiony farmakologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• omega-3 mastné kyseliny MeSH
• rosiglitazon MeSH
• thiazolidindiony MeSH

BACKGROUND: n-3 polyunsaturated fatty acids, namely docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), reduce the risk of cardiovascular disease and can ameliorate many of obesity-associated disorders. We hypothesised that the latter effect will be more pronounced when DHA/EPA is supplemented as phospholipids rather than as triglycerides. METHODOLOGY/PRINCIPAL FINDINGS: In a 'prevention study', C57BL/6J mice were fed for 9 weeks on either a corn oil-based high-fat obesogenic diet (cHF; lipids ∼35% wt/wt), or cHF-based diets in which corn oil was partially replaced by DHA/EPA, admixed either as phospholipids or triglycerides from marine fish. The reversal of obesity was studied in mice subjected to the preceding cHF-feeding for 4 months. DHA/EPA administered as phospholipids prevented glucose intolerance and tended to reduce obesity better than triglycerides. Lipemia and hepatosteatosis were suppressed more in response to dietary phospholipids, in correlation with better bioavailability of DHA and EPA, and a higher DHA accumulation in the liver, white adipose tissue (WAT), and muscle phospholipids. In dietary obese mice, both DHA/EPA concentrates prevented a further weight gain, reduced plasma lipid levels to a similar extent, and tended to improve glucose tolerance. Importantly, only the phospholipid form reduced plasma insulin and adipocyte hypertrophy, while being more effective in reducing hepatic steatosis and low-grade inflammation of WAT. These beneficial effects were correlated with changes of endocannabinoid metabolome in WAT, where phospholipids reduced 2-arachidonoylglycerol, and were more effective in increasing anti-inflammatory lipids such as N-docosahexaenoylethanolamine. CONCLUSIONS/SIGNIFICANCE: Compared with triglycerides, dietary DHA/EPA administered as phospholipids are superior in preserving a healthy metabolic profile under obesogenic conditions, possibly reflecting better bioavalability and improved modulation of the endocannabinoid system activity in WAT.

• MeSH
• analýza rozptylu MeSH
• bílá tuková tkáň metabolismus   MeSH
• biologická dostupnost MeSH
• dieta s vysokým obsahem tuků * MeSH
• endokanabinoidy * MeSH
• fosfolipidy metabolismus   MeSH
• imunohistochemie MeSH
• játra účinky léků   metabolismus   MeSH
• kosterní svaly metabolismus   MeSH
• kvantitativní polymerázová řetězová reakce MeSH
• kyselina eikosapentaenová metabolismus   MeSH
• kyseliny dokosahexaenové metabolismus   MeSH
• metabolomika MeSH
• mikroskopie MeSH
• modulátory kanabinoidních receptorů metabolismus   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• obezita dietoterapie   prevence a kontrola   MeSH
• omega-3 mastné kyseliny aplikace a dávkování   metabolismus   farmakologie   MeSH
• tělesná hmotnost MeSH
• triglyceridy metabolismus   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• endokanabinoidy * MeSH
• fosfolipidy MeSH
• kyselina eikosapentaenová MeSH
• kyseliny dokosahexaenové MeSH
• modulátory kanabinoidních receptorů MeSH
• omega-3 mastné kyseliny MeSH
• triglyceridy MeSH

Combining pharmacological treatments and life style interventions is necessary for effective therapy of major diseases associated with obesity, which are clustered in the metabolic syndrome. Acting via multiple mechanisms, combination treatments may reduce dose requirements and, therefore, lower the risk of adverse side effects, which are usually associated with long-term pharmacological interventions. Our previous study in mice fed high-fat diet indicated additivity in preservation of insulin sensitivity and in amelioration of major metabolic syndrome phenotypes by the combination treatment using n-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFA) and rosiglitazone, i.e. an anti-diabetic drug of the thiazolidinedione (TZD) family. We investigated here whether pioglitazone, a TZD-drug in clinical use, could elicit the additive beneficial effects when combined with n-3 LC-PUFA. Adult male mice (C57BL/6N) were fed an obesogenic corn oil-based high-fat diet (cHF) for 8 weeks, or randomly assigned to various dietary treatments (i) cHF+F, cHF with n-3 LC-PUFA concentrate replacing 15% of dietary lipids; (ii) cHF+ROSI, cHF with 10 mg rosiglitazone/kg diet; (iii) cHF+F+ROSI; (iv) cHF+PIO, cHF with 50 mg pioglitazone/kg diet; and (v) cHF+F+PIO, or chow-fed. Plasma concentrations of 163 metabolites were evaluated using a targeted metabolomics approach. Both TZDs preserved glucose homeostasis and normal plasma lipid levels while inducing adiponectin, with pioglitazone showing better effectiveness. The beneficial effects of TZDs were further augmented by the combination treatments. cHF+F+ROSI but not cHF+F+PIO counteracted development of obesity, in correlation with inducibility of fatty acid β-oxidation, as revealed by the metabolomic analysis. By contrast, only cHF+F+PIO eliminated hepatic steatosis and this treatment also reversed insulin resistance in dietary obese mice. Our results reveal differential effects of rosiglitazone and pioglitazone, unmasked in the combination treatment with n-3 LC-PUFA, and support the notion that n-3 LC-PUFA could be used as add-on treatment to TZDs in order to improve diabetic patient's therapy.

• MeSH
• dietní tuky aplikace a dávkování   MeSH
• homeostáza MeSH
• hypoglykemika aplikace a dávkování   MeSH
• krevní glukóza analýza   MeSH
• lipidy krev   MeSH
• metabolomika MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• obezita prevence a kontrola   MeSH
• omega-3 mastné kyseliny aplikace a dávkování   MeSH
• pioglitazon MeSH
• rosiglitazon MeSH
• thiazolidindiony aplikace a dávkování   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• dietní tuky MeSH
• hypoglykemika MeSH
• krevní glukóza MeSH
• lipidy MeSH
• omega-3 mastné kyseliny MeSH
• pioglitazon MeSH
• rosiglitazon MeSH
• thiazolidindiony MeSH