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

We found previously that white adipose tissue (WAT) hyperplasia in obese mice was limited by dietary omega-3 polyunsaturated fatty acids (omega-3 PUFA). Here we aimed to characterize the underlying mechanism. C57BL/6N mice were fed a high-fat diet supplemented or not with omega-3 PUFA for one week or eight weeks; mice fed a standard chow diet were also used. In epididymal WAT (eWAT), DNA content was quantified, immunohistochemical analysis was used to reveal the size of adipocytes and macrophage content, and lipidomic analysis and a gene expression screen were performed to assess inflammatory status. The stromal-vascular fraction of eWAT, which contained most of the eWAT cells, except for adipocytes, was characterized using flow cytometry. Omega-3 PUFA supplementation limited the high-fat diet-induced increase in eWAT weight, cell number (DNA content), inflammation, and adipocyte growth. eWAT hyperplasia was compromised due to the limited increase in the number of preadipocytes and a decrease in the number of endothelial cells. The number of leukocytes and macrophages was unaffected, but a shift in macrophage polarization towards a less inflammatory phenotype was observed. Our results document that the counteraction of eWAT hyperplasia by omega-3 PUFA in dietary-obese mice reflects an effect on the number of adipose lineage and endothelial cells.

• Klíčová slova
• adipocyte, cellularity, fat, nutrition, obesity, proliferation, white adipose tissue,
• MeSH
• bílá tuková tkáň účinky léků   MeSH
• dieta s vysokým obsahem tuků MeSH
• endoteliální buňky účinky léků   MeSH
• makrofágy účinky léků   patologie   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• omega-3 mastné kyseliny aplikace a dávkování   MeSH
• proliferace buněk účinky léků   MeSH
• tukové buňky cytologie   účinky léků   MeSH
• zánět patologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• omega-3 mastné kyseliny 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

AIMS/HYPOTHESIS: Calorie restriction is an essential component in the treatment of obesity and associated diseases. Long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) act as natural hypolipidaemics, reduce the risk of cardiovascular disease and could prevent the development of obesity and insulin resistance. We aimed to characterise the effectiveness and underlying mechanisms of the combination treatment with LC n-3 PUFA and 10% calorie restriction in the prevention of obesity and associated disorders in mice. METHODS: Male mice (C57BL/6J) were habituated to a corn-oil-based high-fat diet (cHF) for 2 weeks and then randomly assigned to various dietary treatments for 5 weeks or 15 weeks: (1) cHF, ad libitum; (2) cHF with LC n-3 PUFA concentrate replacing 15% (wt/wt) of dietary lipids (cHF + F), ad libitum; (3) cHF with calorie restriction (CR; cHF + CR); and (4) cHF + F + CR. Mice fed a chow diet were also studied. RESULTS: We show that white adipose tissue plays an active role in the amelioration of obesity and the improvement of glucose homeostasis by combining LC n-3 PUFA intake and calorie restriction in cHF-fed mice. Specifically in the epididymal fat in the abdomen, but not in other fat depots, synergistic induction of mitochondrial oxidative capacity and lipid catabolism was observed, resulting in increased oxidation of metabolic fuels in the absence of mitochondrial uncoupling, while low-grade inflammation was suppressed, reflecting changes in tissue levels of anti-inflammatory lipid mediators, namely 15-deoxy-Δ(12,15)-prostaglandin J(2) and protectin D1. CONCLUSIONS/INTERPRETATION: White adipose tissue metabolism linked to its inflammatory status in obesity could be modulated by combination treatment using calorie restriction and dietary LC n-3 PUFA to improve therapeutic strategies for metabolic syndrome.

• MeSH
• bílá tuková tkáň účinky léků   metabolismus   MeSH
• dieta s vysokým obsahem tuků MeSH
• dietní tuky farmakologie   MeSH
• energetický metabolismus účinky léků   MeSH
• imunohistochemie MeSH
• kalorická restrikce * MeSH
• kvantitativní polymerázová řetězová reakce MeSH
• kyseliny dokosahexaenové metabolismus   MeSH
• metabolismus lipidů účinky léků   MeSH
• myši obézní MeSH
• myši MeSH
• omega-3 mastné kyseliny farmakologie   MeSH
• prostaglandin D2 analogy a deriváty   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 9-deoxy-delta-9-prostaglandin D2 MeSH Prohlížeč
• dietní tuky MeSH
• kyseliny dokosahexaenové MeSH
• omega-3 mastné kyseliny MeSH
• prostaglandin D2 MeSH
• protectin D1 MeSH Prohlížeč

BACKGROUND: Long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) of marine origin exert multiple beneficial effects on health. Our previous study in mice showed that reduction of adiposity by LC n-3 PUFA was associated with both, a shift in adipose tissue metabolism and a decrease in tissue cellularity. The aim of this study was to further characterize the effects of LC n-3 PUFA on fat cell proliferation and differentiation in obese mice. METHODS: A model of inducible and reversible lipoatrophy (aP2-Cre-ERT2 PPARγL2/L2 mice) was used, in which the death of mature adipocytes could be achieved by a selective ablation of peroxisome proliferator-activated receptor γ in response to i.p. injection of tamoxifen. Before the injection, obesity was induced in male mice by 8-week-feeding a corn oil-based high-fat diet (cHF) and, subsequently, mice were randomly assigned (day 0) to one of the following groups: (i) mice injected by corn-oil-vehicle only, i.e."control" mice, and fed cHF; (ii) mice injected by tamoxifen in corn oil, i.e. "mutant" mice, fed cHF; (iii) control mice fed cHF diet with15% of dietary lipids replaced by LC n-3 PUFA concentrate (cHF+F); and (iv) mutant mice fed cHF+F. Blood and tissue samples were collected at days 14 and 42. RESULTS: Mutant mice achieved a maximum weight loss within 10 days post-injection, followed by a compensatory body weight gain, which was significantly faster in the cHF as compared with the cHF+F mutant mice. Also in control mice, body weight gain was depressed in response to dietary LC n-3 PUFA. At day 42, body weights in all groups stabilized, with no significant differences in adipocyte size between the groups, although body weight and adiposity was lower in the cHF+F as compared with the cHF mice, with a stronger effect in the mutant than in control mice. Gene expression analysis documented depression of adipocyte maturation during the reconstitution of adipose tissue in the cHF+F mutant mice. CONCLUSION: Dietary LC n-3 PUFA could reduce both hypertrophy and hyperplasia of fat cells in vivo. Results are in agreement with the involvement of fat cell turnover in control of adiposity.

• MeSH
• cyklooxygenasy genetika   metabolismus   MeSH
• epididymis metabolismus   patologie   MeSH
• exprese genu MeSH
• genový knockout MeSH
• kukuřičný olej škodlivé účinky   MeSH
• myši transgenní MeSH
• myši MeSH
• obezita chemicky indukované   prevence a kontrola   MeSH
• omega-3 mastné kyseliny farmakologie   MeSH
• PPAR alfa genetika   metabolismus   MeSH
• PPAR gama genetika   MeSH
• PPARGC1A MeSH
• preklinické hodnocení léčiv MeSH
• proliferace buněk účinky léků   MeSH
• proteiny genetika   metabolismus   MeSH
• stearyl-CoA-desaturasa genetika   metabolismus   MeSH
• trans-aktivátory genetika   metabolismus   MeSH
• transkripční faktory MeSH
• tukové buňky účinky léků   patologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• cyclooxygenase-3 MeSH Prohlížeč
• cyklooxygenasy MeSH
• fat-specific protein 27, mouse MeSH Prohlížeč
• kukuřičný olej MeSH
• omega-3 mastné kyseliny MeSH
• PPAR alfa MeSH
• PPAR gama MeSH
• Ppargc1a protein, mouse MeSH Prohlížeč
• PPARGC1A MeSH
• proteiny MeSH
• Scd1 protein, mouse MeSH Prohlížeč
• stearyl-CoA-desaturasa MeSH
• trans-aktivátory MeSH
• transkripční faktory MeSH

OBJECTIVE: The induction of obesity, dyslipidemia, and insulin resistance by high-fat diet in rodents can be prevented by n-3 long-chain polyunsaturated fatty acids (LC-PUFAs). We tested a hypothesis whether AMP-activated protein kinase (AMPK) has a role in the beneficial effects of n-3 LC-PUFAs. RESEARCH DESIGN AND METHODS: Mice with a whole-body deletion of the α2 catalytic subunit of AMPK (AMPKα2(-/-)) and their wild-type littermates were fed on either a low-fat chow, or a corn oil-based high-fat diet (cHF), or a cHF diet with 15% lipids replaced by n-3 LC-PUFA concentrate (cHF+F). RESULTS: Feeding a cHF diet induced obesity, dyslipidemia, hepatic steatosis, and whole-body insulin resistance in mice of both genotypes. Although cHF+F feeding increased hepatic AMPKα2 activity, the body weight gain, dyslipidemia, and the accumulation of hepatic triglycerides were prevented by the cHF+F diet to a similar degree in both AMPKα2(-/-) and wild-type mice in ad libitum-fed state. However, preservation of hepatic insulin sensitivity by n-3 LC-PUFAs required functional AMPKα2 and correlated with the induction of adiponectin and reduction in liver diacylglycerol content. Under hyperinsulinemic-euglycemic conditions, AMPKα2 was essential for preserving low levels of both hepatic and plasma triglycerides, as well as plasma free fatty acids, in response to the n-3 LC-PUFA treatment. CONCLUSIONS: Our results show that n-3 LC-PUFAs prevent hepatic insulin resistance in an AMPKα2-dependent manner and support the role of adiponectin and hepatic diacylglycerols in the regulation of insulin sensitivity. AMPKα2 is also essential for hypolipidemic and antisteatotic effects of n-3 LC-PUFA under insulin-stimulated conditions.

• MeSH
• buněčné kultury MeSH
• dieta s omezením tuků MeSH
• dietní tuky farmakologie   MeSH
• glykemický clamp MeSH
• hepatocyty cytologie   fyziologie   MeSH
• hyperinzulinismus MeSH
• inzulinová rezistence MeSH
• játra účinky léků   enzymologie   fyziologie   MeSH
• metabolický syndrom prevence a kontrola   MeSH
• myši knockoutované MeSH
• myši MeSH
• nenasycené mastné kyseliny metabolismus   farmakologie   MeSH
• omega-3 mastné kyseliny metabolismus   terapeutické užití   MeSH
• podjednotky proteinů metabolismus   MeSH
• proteinkinasy aktivované AMP nedostatek   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• dietní tuky MeSH
• nenasycené mastné kyseliny MeSH
• omega-3 mastné kyseliny MeSH
• podjednotky proteinů MeSH
• Prkaa2 protein, mouse MeSH Prohlížeč
• proteinkinasy aktivované AMP MeSH