Enriching the Starter Diet in n-3 Polyunsaturated Fatty Acids Reduces Adipocyte Size in Broiler Chicks.
ABSTRACT: Epidemiologic studies associate perinatal intake of eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) with reduced adiposity in children, suggesting that these fatty acids may alter adipose tissue development. The objective of this study was to determine whether enriching the perinatal diet in EPA and DHA reduces fat deposition in young chicks. Cobb 500 broiler chicks were fed isocaloric diets containing fat (8% wt:wt) from fish oil (FO), lard, canola oil, or flaxseed oil from 7 to 30 d of age. Adiposity (abdominal fat pad weight/body weight) at 30 d was not significantly affected by diet, but FO significantly reduced adipocyte size, increasing the abundance of small adipocytes. Plasma nonesterified fatty acid concentrations suggest that reduced adipocyte size was due, in part, to enhanced mobilization of fatty acids from adipose tissue. Our work indicates that dietary EPA and DHA effectively reduce the size of developing adipocytes in juveniles, which may limit adipose deposition and provide metabolic benefits.
Project description:Maternal intake of eicosapentaenoic acid (EPA; 20:5 n-3) and docosahexaenoic acid (22:6 n-3) has been associated with reduced adiposity in children, suggesting the possibility to program adipose development through dietary fatty acids before birth. This study determined if enriching the maternal diet in fish oil, the primary source of EPA and DHA, affected adipose development in offspring. Broiler chickens were used because they are obesity-prone, and because fatty acids provided to the embryo can be manipulated through the hen diet. Hens were fed diets supplemented (2.8% wt:wt) with corn oil (CO; n-6) or fish oil (FO; n-3) for 28 d. Chicks from both maternal diet groups were fed the same diet after hatch. Maternal FO consumption enriched chick adipose tissue in EPA and DHA and reduced adiposity by promoting more, but smaller, adipocytes. This adipocyte profile was paralleled by upregulated expression of the adipogenic regulator PPARG and its co-activator PPARGC1B, and reduced expression of LPL. Proteomics identified 95 differentially abundant proteins between FO and CO adipose tissue, including components of glucose metabolism, lipid droplet trafficking, and cytoskeletal organization. These results demonstrate that the maternal dietary fatty acid profile programs offspring adipose development.
Project description:Eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) supplementation has beneficial cardiovascular effects, but postprandial influences of these individual fatty acids are unclear.The primary objective was to determine the vascular effects of EPA + DHA compared with DHA only during postprandial lipemia relative to control high-oleic acid meals; the secondary objective was to characterize the effects of linoleic acid-enriched high-fat meals relative to the control meal.We conducted a randomized, controlled, double-blind crossover trial of 4 high-fat (75-g) meals containing 1) high-oleic acid sunflower oil (HOS; control), 2) HOS + fish oil (FO; 5 g EPA and DHA), 3) HOS + algal oil (AO; 5 g DHA), and 4) high-linoleic acid sunflower oil (HLS) in 16 healthy men (aged 35-70 y) with higher than optimal fasting triacylglycerol concentrations (mean ± SD triacylglycerol, 1.9 ± 0.5 mmol/L).Elevations in triacylglycerol concentration relative to baseline were slightly reduced after FO and HLS compared with the HOS control (P < 0.05). The characteristic decrease from baseline in plasma nonesterified fatty acids after a mixed meal was inhibited after AO (? 0-3 h, P < 0.05). HLS increased the augmentation index compared with the other test meals (P < 0.05), although the digital volume pulse-reflection index was not significantly different. Plasma 8-isoprostane F2? analysis revealed opposing effects of FO (increased) and AO (reduced) compared with the control (P < 0.05). No differences in nitric oxide metabolites were observed.These data show differential postprandial 8-isoprostane F2? responses to high-fat meals containing EPA + DHA-rich fish oil compared with DHA-rich AO, but these differences were not associated with consistent effects on postprandial vascular function or lipemia. More detailed analyses of polyunsaturated fatty acid-derived lipid mediators are required to determine possible divergent functional effects of single meals rich in either DHA or EPA. This trial was registered at clinicaltrials.gov as NCT01618071.
Project description:Overactivity and/or dysregulation of the endocannabinoid system (ECS) contribute to development of obesity. In vitro studies indicate a regulatory role for the cannabinoid receptor 1 (CB1) in adipocyte function and CB1-receptor deficient (CB1-/-) mice are resistant to high fat diet-induced obesity. Whether this phenotype of CB1-/- mice is related to altered fat metabolism in adipose tissue is unknown.We evaluated adipose tissue differentiation/proliferation markers and quantified lipogenic and lipolytic activities in fat tissues of CB1-/- and CB1+/+ mice fed a high-fat (HF) or a high-fat/fish oil (HF/FO) diet as compared to animals receiving a low-fat chow diet. Comparison between HF diet and HF/FO diet allowed to investigate the influence of dietary fat quality on adipose tissue biology in relation to CB1 functioning.The adiposity-resistant phenotype of the CB1-/- mice was characterized by reduced fat mass and adipocyte size in HF and HF/FO-fed CB1-/- mice in parallel to a significant increase in energy expenditure as compared to CB1+/+ mice. The expression levels of adipocyte differentiation and proliferation markers were however maintained in these animals. Consistent with unaltered lipogenic gene expression, the fatty acid synthesis rates in adipose tissues from CB1-/- and CB1+/+ mice were unchanged. Whole-body and adipose-specific lipoprotein lipase (LPL) activities were also not altered in CB1-/- mice.These findings indicate that protection against diet-induced adiposity in CB1-deficient mice is not related to changes in adipocyte function per se, but rather results from increased energy dissipation by oxidative and non-oxidative pathways.
Project description:Excess energy intake can trigger an uncontrolled inflammatory response, leading to systemic low-grade inflammation and metabolic disturbances that are hypothesised to contribute to cardiovascular disease and type 2 diabetes. The long chain n-3 polyunsaturated fatty acids (LC n-3 PUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are suggested to mitigate this inflammatory response, but the mechanisms are unclear, especially at the tissue level. Adipose tissues, the first tissues to give an inflammatory response, may be an important target site of action for EPA and DHA. To evaluate the effects of EPA and DHA in white and brown adipose tissues, we fed male C57Bl/6J mice either a high fat diet (HFD) with 5% corn oil, an HFD with 40% of the corn oil substituted for purified EPA and DHA triglycerides (HFD-ED), or normal chow, for 8 weeks. Fatty acid profiling and transcriptomics were used to study how EPA and DHA affect retroperitoneal white and brown adipose tissues. HFD-ED fed mice showed reduced lipid accumulation and levels of the pro-inflammatory fatty acid arachidonic acid in both white and brown adipose tissues, compared with HFD-corn oil fed animals. The transcriptomic analysis showed changes in ?-oxidation pathways, supporting the decreased lipid accumulation in the HFD-ED fed mice. Therefore, our data suggests that EPA and DHA supplementation of a high fat diet may be anti-inflammatory, as well as reduce lipid accumulation in adipose tissues.
Project description:BACKGROUND: Marine derived oils are rich in long-chain polyunsaturated omega-3 fatty acids, in particular eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which have long been associated with health promoting effects such as reduced plasma lipid levels and anti-inflammatory effects. Krill oil (KO) is a novel marine oil on the market and is also rich in EPA and DHA, but the fatty acids are incorporated mainly into phospholipids (PLs) rather than triacylglycerols (TAG). This study compares the effects of fish oil (FO) and KO on gene regulation that influences plasma and liver lipids in a high fat diet mouse model. METHODS: Male C57BL/6J mice were fed either a high-fat diet (HF) containing 24% (wt/wt) fat (21.3% lard and 2.3% soy oil), or the HF diet supplemented with FO (15.7% lard, 2.3% soy oil and 5.8% FO) or KO (15.6% lard, 2.3% soy oil and 5.7% KO) for 6 weeks. Total levels of cholesterol, TAG, PLs, and fatty acid composition were measured in plasma and liver. Gene regulation was investigated using quantitative PCR in liver and intestinal epithelium. RESULTS: Plasma cholesterol (esterified and unesterified), TAG and PLs were significantly decreased with FO. Analysis of the plasma lipoprotein particles indicated that the lipid lowering effect by FO is at least in part due to decreased very low density lipoprotein (VLDL) content in plasma with subsequent liver lipid accumulation. KO lowered plasma non-esterified fatty acids (NEFA) with a minor effect on fatty acid accumulation in the liver. In spite of a lower omega-3 fatty acid content in the KO supplemented diet, plasma and liver PLs omega-3 levels were similar in the two groups, indicating a higher bioavailability of omega-3 fatty acids from KO. KO more efficiently decreased arachidonic acid and its elongation/desaturation products in plasma and liver. FO mainly increased the expression of several genes involved in fatty acid metabolism, while KO specifically decreased the expression of genes involved in the early steps of isoprenoid/cholesterol and lipid synthesis. CONCLUSIONS: The data show that both FO and KO promote lowering of plasma lipids and regulate lipid homeostasis, but with different efficiency and partially via different mechanisms.
Project description:Dietary intake of linoleic acid (LA) has increased dramatically during the twentieth century and is associated with a greater prevalence of obesity. Vegetable oils are recognised as suitable alternatives to fish oil (FO) in feed for Atlantic salmon (Salmo salar L.) but introduce high amounts of LA in the salmon fillet. The effect on fish consumers of such a replacement remains to be elucidated. Here, we investigate the effect of excessive dietary LA from soyabean oil (SO) on endocannabinoid levels in Atlantic salmon and mice, and study the metabolic effects in mice when SO replaces FO in feed for Atlantic salmon. Atlantic salmon were fed FO and SO for 6 months, and the salmon fillet was used to produce feed for mice. Male C57BL/6J mice were fed diets of 35% of energy as fat based on FO- and SO-enriched salmon for 16 weeks. We found that replacing FO with SO in feed for Atlantic salmon increased LA, arachidonic acid (AA), decreased EPA and DHA, elevated the endocannabinoids 2-arachidonoylglycerol (2-AG) and anandamide (AEA), and increased TAG accumulation in the salmon liver. In mice, the SO salmon diet increased LA and AA and decreased EPA and DHA in the liver and erythrocyte phospholipids, and elevated 2-AG and AEA associated with increased feed efficiency, weight gain and adipose tissue inflammation compared with mice fed the FO salmon diet. In conclusion, excessive dietary LA elevates endocannabinoids in the liver of salmon and mice, and increases weight gain and counteracts the anti-inflammatory properties of EPA and DHA in mice.
Project description:Low hepatic content of n-3 PUFA has been associated with NAFLD in humans. Whether this is associated with reduced dietary intake or increased turnover of these FA is not clear. We have here investigated the effects of dietary fat quality on hepatic lipid storage and transcriptomics over time.To investigate the effects of quality of fat in a high fat diet (HFD) over time on hepatic lipid storage and liver transcriptomics.Male C57BL/6J mice were fed control, HFD-eicosapentaenoic acid (EPA)/ docosahexaenoic acid (DHA) or HFD-corn oil diet for 8 or 12 weeks. Body weight, body composition, plasma and hepatic triglyceride contents were measured. Hepatic transcriptomes were analysed by microarray followed by gene-set enrichment analyses. At 8 weeks, the HFD-corn oil mice had higher body weight and adipose depot mass than the HFD-EPA/DHA but there were no differences at 12 weeks. Hepatic triglyceride content was lower in HFD-EPA/DHA fed compared with the HFD-corn oil fed mice at both time-points. Enrichment analyses of the hepatic transcriptomes showed that lipid/fatty acid biosynthesis; transport and homeostasis were lower in the HFD-EPA/DHA fed compared with the HFD-corn oil fed mice. Genes encoding proteins associated to cytoplasmic lipid droplets were expressed at higher levels in livers from the HFD-corn oil compared to HFD-EPA/DHA mice.Dietary EPA and DHA counteracted development of HFD-induced fatty liver. The liver transcriptome data implicate that the quality of dietary fat could modulate Ppar-related gene expression that in turn affects hepatic lipid storage and maintenance of metabolic health.
Project description:Context:The NRLP3 inflammasome is a multiprotein danger-sensing complex that serves as a critical link between obesity-related adipose inflammation and insulin resistance and has been shown in animal models to be inhibited by fish oil-derived long chain omega-3 polyunsaturated fatty acids (n-3 PUFA). Objective:We conducted a clinical trial and in vitro experiments to test our hypothesis that n-3 PUFA suppress NLRP3 inflammasome in human obesity through downregulation of inflammasome gene expression in adipocytes and macrophages. Design:Placebo-controlled clinical trial and in vitro coculture experiments with primary human adipocytes (from biopsy specimens) and human THP-1 monocyte-derived macrophages treated with eicosapentaenoic acid (EPA) and/or docosahexaenoic acid (DHA) vs vehicle control. Setting:General community, research laboratory. Patients and Other Participants:Obese (body mass index ≥ 30 kg/m2), nondiabetic males and females age 18 to 50. N = 25. Interventions:Clinical trial: Eight-week treatment with 4 g Lovaza (EPA and DHA) or placebo. Cells culture: EPA and/or DHA at 100 µg/mL or vehicle control in culture medium. Main Outcome Measures:Adipose tissue or adipocyte/macrophage mRNA expression of IL-1β and IL-18 and circulating IL-18 levels. Results:Treatment of obese human subjects with fish oil supplements reduced expression of adipose inflammatory genes including inflammasome-associated IL-18 and IL-1β and circulating IL-18 levels. Both EPA and DHA reduced inflammasome gene expression in obese human adipose and human adipocyte and macrophages. Conclusions:N-3 PUFA reduce NLRP3 inflammasome in human adipose through downregulation of gene expression in adipocytes and monocytes/macrophages and has potential as nutritional therapeutic agent in prevention of obesity-related inflammation.
Project description: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.
Project description:Dietary supplementation with ?-3 polyunsaturated fatty acids (?-3 PUFAs), specifically the fatty acids docosahexaenoic acid (DHA; 22:6 ?-3) and eicosapentaenoic acid (EPA; 20:5 ?-3), is known to have beneficial health effects including improvements in glucose and lipid homeostasis and modulation of inflammation. To evaluate the efficacy of two different sources of ?-3 PUFAs, we performed gene expression profiling in the liver of mice fed diets supplemented with either fish oil (FO) or krill oil (KO). We found that ?-3 PUFA supplements derived from a phospholipid krill fraction (KO) downregulated the activity of pathways involved in hepatic glucose production as well as lipid and cholesterol synthesis. The data also suggested that KO-supplementation increases the activity of the mitochondrial respiratory chain. Surprisingly, an equimolar dose of EPA and DHA derived from FO modulated fewer pathways than a KO-supplemented diet and did not modulate key metabolic pathways regulated by KO, including glucose metabolism, lipid metabolism and the mitochondrial respiratory chain. Moreover, FO upregulated the cholesterol synthesis pathway, which was the opposite effect of krill-supplementation. Neither diet elicited changes in plasma levels of lipids, glucose, or insulin, probably because the mice used in this study were young and were fed a low-fat diet. Further studies of KO-supplementation using animal models of metabolic disorders and/or diets with a higher level of fat may be required to observe these effects.