Obesity adversely affects bone and fat metabolism in mice and humans. Omega-3 polyunsaturated fatty acids (omega-3 PUFAs) have been shown to improve glucose metabolism and bone homeostasis in obesity. However, the impact of omega-3 PUFAs on bone marrow adipose tissue (BMAT) and bone marrow stromal cell (BMSC) metabolism has not been intensively studied yet. In the present study we demonstrated that omega-3 PUFA supplementation in high fat diet (HFD + F) improved bone parameters, mechanical properties along with decreased BMAT in obese mice when compared to the HFD group. Primary BMSCs isolated from HFD + F mice showed decreased adipocyte and higher osteoblast differentiation with lower senescent phenotype along with decreased osteoclast formation suggesting improved bone marrow microenvironment promoting bone formation in mice. Thus, our study highlights the beneficial effects of omega-3 PUFA-enriched diet on bone and cellular metabolism and its potential use in the treatment of metabolic bone diseases.

• MeSH
• Adiposity MeSH
• Bone and Bones metabolism   MeSH
• Bone Marrow * metabolism   MeSH
• Humans MeSH
• Disease Models, Animal MeSH
• Mice MeSH
• Obesity complications   prevention & control   metabolism   MeSH
• Fatty Acids, Omega-3 * pharmacology   metabolism   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Fatty Acids, Omega-3 * MeSH

Long-chain n-3 polyunsaturated fatty acids (Omega-3) and anti-diabetic drugs thiazolidinediones (TZDs) exhibit additive effects in counteraction of dietary obesity and associated metabolic dysfunctions in mice. The underlying mechanisms need to be clarified. Here, we aimed to learn whether the futile cycle based on the hydrolysis of triacylglycerol and re-esterification of fatty acids (TAG/FA cycling) in white adipose tissue (WAT) could be involved. We compared Omega-3 (30 mg/g diet) and two different TZDs-pioglitazone (50 mg/g diet) and a second-generation TZD, MSDC-0602K (330 mg/g diet)-regarding their effects in C57BL/6N mice fed an obesogenic high-fat (HF) diet for 8 weeks. The diet was supplemented or not by the tested compound alone or with the two TZDs combined individually with Omega-3. Activity of TAG/FA cycle in WAT was suppressed by the obesogenic HF diet. Additive effects in partial rescue of TAG/FA cycling in WAT were observed with both combined interventions, with a stronger effect of Omega-3 and MSDC-0602K. Our results (i) supported the role of TAG/FA cycling in WAT in the beneficial additive effects of Omega-3 and TZDs on metabolism of diet-induced obese mice, and (ii) showed differential modulation of WAT gene expression and metabolism by the two TZDs, depending also on Omega-3.

• Keywords
• adipocytes, glucose homeostasis, insulin, lipogenesis, obesity,
• MeSH
• Adipose Tissue, White metabolism   MeSH
• Diet, High-Fat MeSH
• Hypoglycemic Agents pharmacology   MeSH
• Lipogenesis drug effects   MeSH
• Fatty Acids metabolism   MeSH
• Lipid Metabolism drug effects   MeSH
• Mice, Inbred C57BL MeSH
• Mice, Obese MeSH
• Mice MeSH
• Obesity drug therapy   metabolism   MeSH
• Fatty Acids, Omega-3 administration & dosage   pharmacology   MeSH
• Pioglitazone pharmacology   MeSH
• Thiazolidinediones administration & dosage   pharmacology   MeSH
• Triglycerides metabolism   MeSH
• Adipocytes drug effects   MeSH
• Animals MeSH
• Check Tag
• Male MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Hypoglycemic Agents MeSH
• Fatty Acids MeSH
• Fatty Acids, Omega-3 MeSH
• Pioglitazone MeSH
• Thiazolidinediones MeSH
• Triglycerides MeSH

Fillets from marine fish species contain n-3 polyunsaturated fatty acids (PUFAs) in the form of phospholipids (PLs). To investigate the importance of PL-bound n-3 PUFAs in mediating the anti-obesogenic effect of lean seafood, we compared the anti-obesogenic properties of fillets from cod with fillets from pangasius, a fresh water fish with a very low content of PL-bound n-3 PUFAs. We prepared high-fat/high-protein diets using chicken, cod and pangasius as the protein sources, and fed male C57BL/6J mice these diets for 12 weeks. Mice fed the diet containing cod gained less adipose tissue mass and had smaller white adipocytes than mice fed the chicken-containing diet, whereas mice fed the pangasius-containing diet were in between mice fed the chicken-containing diet and mice fed the cod-containing diet. Of note, mice fed the pangasius-containing diet exhibited reduced glucose tolerance compared to mice fed the cod-containing diet. Although the sum of marine n-3 PUFAs comprised less than 2% of the total fatty acids in the cod-containing diet, this was sufficient to significantly increase the levels of eicosapentaenoic acid (EPA) and docosahexaenoic acids (DHA) in mouse tissues and enhance production of n-3 PUFA-derived lipid mediators as compared with mice fed pangasius or chicken.

• Keywords
• DHA, EPA, endocannabinoids, marine protein source, n-3 PUFA, nutrition, obesity and mice, phospholipids, seafood,
• MeSH
• Diet, High-Protein methods   MeSH
• Diet, High-Fat methods   MeSH
• Poultry Products MeSH
• Gadus morhua * MeSH
• Eicosapentaenoic Acid metabolism   MeSH
• Docosahexaenoic Acids metabolism   MeSH
• Anti-Obesity Agents analysis   MeSH
• Fatty Acids analysis   MeSH
• Lipid Metabolism MeSH
• Mice, Inbred C57BL MeSH
• Mice MeSH
• Fatty Acids, Omega-3 analysis   MeSH
• Seafood analysis   MeSH
• Catfishes * MeSH
• Adipose Tissue metabolism   MeSH
• Animals MeSH
• Check Tag
• Male MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Eicosapentaenoic Acid MeSH
• Docosahexaenoic Acids MeSH
• Anti-Obesity Agents MeSH
• Fatty Acids MeSH
• Fatty Acids, Omega-3 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.

• Keywords
• Omega-3 index, Omega-3 phospholipids, high-fat diet, krill oil, small intestine,
• MeSH
• Diet, High-Fat * MeSH
• Erythrocyte Membrane metabolism   MeSH
• Euphausiacea MeSH
• Phospholipids administration & dosage   MeSH
• Blood Glucose analysis   MeSH
• Fatty Acids metabolism   MeSH
• Lipid Metabolism drug effects   MeSH
• Mice, Obese MeSH
• Oils MeSH
• Fatty Acids, Omega-3 administration & dosage   MeSH
• Oxidation-Reduction MeSH
• Intestines anatomy & histology   MeSH
• Intestinal Mucosa metabolism   MeSH
• Body Weight MeSH
• Triglycerides administration & dosage   MeSH
• Animals MeSH
• Check Tag
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Phospholipids MeSH
• Blood Glucose MeSH
• Fatty Acids MeSH
• Oils MeSH
• Fatty Acids, Omega-3 MeSH
• Triglycerides 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.

• Keywords
• adipocyte, cellularity, fat, nutrition, obesity, proliferation, white adipose tissue,
• MeSH
• Adipose Tissue, White drug effects   MeSH
• Diet, High-Fat MeSH
• Endothelial Cells drug effects   MeSH
• Macrophages drug effects   pathology   MeSH
• Mice, Inbred C57BL MeSH
• Mice MeSH
• Fatty Acids, Omega-3 administration & dosage   MeSH
• Cell Proliferation drug effects   MeSH
• Adipocytes cytology   drug effects   MeSH
• Inflammation pathology   MeSH
• Animals MeSH
• Check Tag
• Male MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Fatty Acids, Omega-3 MeSH

Fatty acid (FA)-stimulated insulin secretion (FASIS) is reviewed here in contrast to type 2 diabetes etiology, resulting from FA overload, oxidative stress, intermediate hyperinsulinemia, and inflammation, all converging into insulin resistance. Focusing on pancreatic islet β-cells, we compare the physiological FA roles with the pathological ones. Considering FAs not as mere amplifiers of glucose-stimulated insulin secretion (GSIS), but as parallel insulin granule exocytosis inductors, partly independent of the KATP channel closure, we describe the FA initiating roles in the prediabetic state that is induced by retardations in the glycerol-3-phosphate (glucose)-promoted glycerol/FA cycle and by the impaired GPR40/FFA1 (free FA1) receptor pathway, specifically in its amplification by the redox-activated mitochondrial phospholipase, iPLA2γ. Also, excessive dietary FAs stimulate intestine enterocyte incretin secretion, further elevating GSIS, even at low glucose levels, thus contributing to diabetic hyperinsulinemia. With overnutrition and obesity, the FA overload causes impaired GSIS by metabolic dysbalance, paralleled by oxidative and metabolic stress, endoplasmic reticulum stress and numerous pro-apoptotic signaling, all leading to decreased β-cell survival. Lipotoxicity is exerted by saturated FAs, whereas ω-3 polyunsaturated FAs frequently exert antilipotoxic effects. FA-facilitated inflammation upon the recruitment of excess M1 macrophages into islets (over resolving M2 type), amplified by cytokine and chemokine secretion by β-cells, leads to an inevitable failure of pancreatic β-cells.

• Keywords
• GPR40, fatty acid-stimulated insulin secretion, fatty acids, lipotoxicity, low-grade inflammation, oxidative stress, pancreatic β-cells, type 2 diabetes,
• MeSH
• Insulin-Secreting Cells * metabolism   pathology   MeSH
• Hyperinsulinism * metabolism   pathology   MeSH
• Insulin metabolism   MeSH
• Insulin Resistance * MeSH
• Humans MeSH
• Fatty Acids metabolism   MeSH
• Oxidative Stress * MeSH
• Insulin Secretion MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• Insulin MeSH
• Fatty Acids MeSH

Characterizations of fatty acids composition in % of total methylester of fatty acids (FAMEs) of fourteen vegetable oils--safflower, grape, silybum marianum, hemp, sunflower, wheat germ, pumpkin seed, sesame, rice bran, almond, rapeseed, peanut, olive, and coconut oil--were obtained by using gas chromatography (GC). Saturated (SFA), monounsaturated (MUFA) and polyunsaturated fatty acids (PUFA), palmitic acid (C16:0; 4.6%-20.0%), oleic acid (C18:1; 6.2%-71.1%) and linoleic acid (C18:2; 1.6%-79%), respectively, were found predominant. The nutritional aspect of analyzed oils was evaluated by determination of the energy contribution of SFAs (19.4%-695.7% E(RDI)), PUFAs (10.6%-786.8% E(RDI)), n-3 FAs (4.4%-117.1% E(RDI)) and n-6 FAs (1.8%-959.2% E(RDI)), expressed in % E(RDI) of 1 g oil to energy recommended dietary intakes (E(RDI)) for total fat (E(RDI)--37.7 kJ/g). The significant relationship between the reported data of total fat, SFAs, MUFAs and PUFAs intakes (% E(RDI)) for adults and mortality caused by coronary heart diseases (CHD) and cardiovascular diseases (CVD) in twelve countries has not been confirmed by Spearman's correlations.

• Keywords
• Spearman’s correlation, cardiovascular diseases, coronary heart diseases, fatty acids, vegetable oils,
• MeSH
• Energy Intake * MeSH
• Cardiovascular Diseases epidemiology   mortality   prevention & control   MeSH
• Humans MeSH
• Fatty Acids administration & dosage   analysis   MeSH
• Plant Oils administration & dosage   chemistry   MeSH
• Nutrition Policy * MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Fatty Acids MeSH
• Plant Oils MeSH

Total lipid contents of green (Chlorella pyrenoidosa, C), red (Porphyra tenera, N; Palmaria palmata, D), and brown (Laminaria japonica, K; Eisenia bicyclis, A; Undaria pinnatifida, W, WI; Hizikia fusiformis, H) commercial edible algal and cyanobacterial (Spirulina platensis, S) products, and autotrophically cultivated samples of the green microalga Chlorella kessleri (CK) and the cyanobacterium Spirulina platensis (SP) were determined using a solvent mixture of methanol/chloroform/water (1:2:1, v/v/v, solvent I) and n-hexane (solvent II). Total lipid contents ranged from 0.64% (II) to 18.02% (I) by dry weight and the highest total lipid content was observed in the autotrophically cultivated cyanobacterium Spirulina platensis. Solvent mixture I was found to be more effective than solvent II. Fatty acids were determined by gas chromatography of their methyl esters (% of total FAMEs). Generally, the predominant fatty acids (all results for extractions with solvent mixture I) were saturated palmitic acid (C16:0; 24.64%-65.49%), monounsaturated oleic acid (C18:1(n-9); 2.79%-26.45%), polyunsaturated linoleic acid (C18:2(n-6); 0.71%-36.38%), α-linolenic acid (C18:3(n-3); 0.00%-21.29%), γ-linolenic acid (C18:3(n-6); 1.94%-17.36%), and arachidonic acid (C20:4(n-6); 0.00%-15.37%). The highest content of ω-3 fatty acids (21.29%) was determined in Chlorella pyrenoidosa using solvent I, while conversely, the highest content of ω-6 fatty acids (41.42%) was observed in Chlorella kessleri using the same solvent.

• MeSH
• Food Analysis MeSH
• Chlorophyta chemistry   MeSH
• alpha-Linolenic Acid chemistry   MeSH
• Linoleic Acid chemistry   MeSH
• Palmitic Acid chemistry   MeSH
• Lipids chemistry   isolation & purification   MeSH
• Seaweed chemistry   MeSH
• Fatty Acids, Omega-3 chemistry   MeSH
• Solvents chemistry   MeSH
• Cyanobacteria chemistry   MeSH
• Fresh Water MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• alpha-Linolenic Acid MeSH
• Linoleic Acid MeSH
• Palmitic Acid MeSH
• Lipids MeSH
• Fatty Acids, Omega-3 MeSH
• Solvents MeSH

OBJECTIVE: Resolution of low-grade inflammation of white adipose tissue (WAT) is one of the keys for amelioration of obesity-associated metabolic dysfunctions. We focused on the identification of adipokines, which could be involved at the early stages of resolution of WAT inflammation. METHODS AND PROCEDURE: Male C57BL/6J mice with obesity induced in response to a 22-week feeding corn oil-based high-fat (cHF) diet were divided into four groups and were fed with, for 2 weeks, control cHF diet or cHF-based diets supplemented with: (i) concentrate of n-3 long-chain polyunsaturated fatty acids, mainly eicosapentaenoic and docosahexaenoic acids (cHF+F); (ii) thiazolidinedione drug rosiglitazone (cHF+TZD); and (iii) both compounds (cHF+F+TZD). RESULTS: The short-term combined intervention exerted additive effect in the amelioration of WAT inflammation in obese mice, namely in the epididymal fat, even in the absence of any changes in either adipocyte volume or fat mass. The combined intervention elicited hypolipidaemic effect and induced adiponectin, whereas the responses to single interventions (cHF+F, cHF+TZD) were less pronounced. In addition, analysis in WAT lysates using protein arrays revealed that the levels of a small set of adipose tissue-related proteins, namely macrophage inflammatory protein 1γ, endoglin, vascular cell adhesion molecule 1 and interleukin 1 receptor antagonist, changed in response to the anti-inflammatory interventions and were strongly reduced in the cHF+F+TZD mice. These results were verified using both the analysis of gene expression and enzyme-linked immunosorbent analysis in WAT lysates. In contrast with adiponectin, which showed changing plasma levels in response to dietary interventions, the levels of the above proteins were affected only in WAT. CONCLUSIONS: We identified several adipose tissue-related proteins, which are locally involved in resolution of low-grade inflammation and remodelling of WAT.

• MeSH
• Adipokines metabolism   MeSH
• Adipose Tissue, White metabolism   pathology   MeSH
• Diet, High-Fat MeSH
• Dietary Fats MeSH
• Enzyme-Linked Immunosorbent Assay MeSH
• Energy Metabolism MeSH
• Immunohistochemistry MeSH
• Real-Time Polymerase Chain Reaction MeSH
• Docosahexaenoic Acids pharmacology   MeSH
• Mice, Inbred C57BL MeSH
• Mice, Obese MeSH
• Mice MeSH
• Obesity immunology   pathology   MeSH
• Fatty Acids, Omega-3 pharmacology   MeSH
• Rosiglitazone MeSH
• Thiazolidinediones pharmacology   MeSH
• Adipocytes metabolism   MeSH
• Inflammation pathology   MeSH
• Animals MeSH
• Check Tag
• Male MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Adipokines MeSH
• Dietary Fats MeSH
• Docosahexaenoic Acids MeSH
• Fatty Acids, Omega-3 MeSH
• Rosiglitazone MeSH
• Thiazolidinediones 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
• Diet, High-Fat adverse effects   MeSH
• Glycolysis drug effects   MeSH
• Muscle Fibers, Skeletal drug effects   metabolism   MeSH
• Muscle, Skeletal drug effects   metabolism   MeSH
• Metabolomics MeSH
• Mice, Inbred C57BL MeSH
• Mice MeSH
• Obesity etiology   metabolism   MeSH
• Fatty Acids, Omega-3 pharmacology   MeSH
• Oxidation-Reduction drug effects   MeSH
• Gene Expression Regulation drug effects   MeSH
• Rosiglitazone MeSH
• Drug Synergism MeSH
• Thiazolidinediones pharmacology   MeSH
• Animals MeSH
• Check Tag
• Male MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Fatty Acids, Omega-3 MeSH
• Rosiglitazone MeSH
• Thiazolidinediones MeSH