Discordant Dose-Dependent Metabolic Effects of Eicosapentanoic Acid in Diet-Induced Obese Mice

Pahlavani, Mandana; Ramalingam, Latha; Miller, Emily; Davis, Hilda M.; Scoggin, Shane; Moustaid‐Moussa, Naima

doi:10.3390/nu12051342

Cited by 15 publications

(11 citation statements)

References 68 publications

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“…Even though we observed higher amount of EPA in the liver, we observed similar alterations in adipose and liver supporting that lower amount of FO is sufficient to reproduce these effects. This is line with studies that our lab and others recently published in terms of similar beneficial metabolic effects even with lower doses of EPA enriched FO [43,44]. We used a combination of DHA and EPA (~30 g of FO/diet) which has ~10 g of FO; this is higher than the current recommendation of 4 g/day for people suffering from hypertriglyceridemia [45].…”

Section: Discussionsupporting

confidence: 73%

Sex Differences in Early Programming by Maternal High Fat Diet Induced-Obesity and Fish Oil Supplementation in Mice

et al. 2021

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Pre-pregnancy obesity is a contributing factor for impairments in offspring metabolic health. Interventional strategies during pregnancy are a potential approach to alleviate and/or prevent obesity and obesity related metabolic alterations in the offspring. Fish oil (FO), rich in omega-3 polyunsaturated fatty acids (n-3 PUFAs) exerts metabolic health benefits. However, the role of FO in early life remains still unknown. Hence, this study objective was to determine the effect of FO supplementation in mice from pre-pregnancy through lactation, and to study the post-natal metabolic health effects in gonadal fat and liver of offspring fed high fat (HF) diet with or without FO. Female C57BL6J mice aged 4–5 weeks were fed a HF (45% fat) diet supplemented with or without FO (30 g/kg of diet) and low fat (LF; 10% fat) pre-pregnancy through lactation. After weaning, offspring (male and female) from HF or FO dams either continued the same diet (HF-HF and FO-FO) or switched to the other diet (HF-FO and FO-HF) for 13 weeks, creating four groups of treatment, and LF-LF was used as a control group. Serum, gonadal fat and liver tissue were collected at termination for metabolic analyses. Offspring of both sexes fed HF with or without fish oil gained (p < 0.05) more weight post weaning, compared to LF-LF-fed mice. All the female offspring groups supplemented with FO had reduced body weight compared to the respective male groups. Further, FO-FO supplementation in both sexes (p < 0.05) improved glucose clearance and insulin sensitivity compared to HF-HF. All FO-FO fed mice had significantly reduced adipocyte size compared to HF-HF group in both male and females. Inflammation, measured by mRNA levels of monocyte chemoattractant protein 1 (Mcp1), was reduced (p < 0.05) with FO supplementation in both sexes in gonadal fat and in the liver. Markers of fatty acid synthesis, fatty acid synthase (Fasn) showed no sex specific differences in gonadal fat and liver of mice supplemented with HF. Female mice had lower liver triglycerides than male counterparts. Supplementation of FO in mice improved metabolic health of offspring by lowering markers of lipid synthesis and inflammation.

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Section: Discussionsupporting

confidence: 73%

Sex Differences in Early Programming by Maternal High Fat Diet Induced-Obesity and Fish Oil Supplementation in Mice

et al. 2021

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“…However, EPA and DHA do exert different effects on health 22 . Thus, the supplement type of n ‐3 PUFA is indeed a key factor affecting dietary regulation, while dosage is another factor that should be considered in dietary regulation, because there are concerns that EPA can dose‐dependently affect metabolic outcomes, 23 which have not been fully investigated. The purpose of our study was therefore to evaluate the therapeutic effect of HDTO from the perspective of intake dosage and to further elucidate its anti‐obesity effects by metabolomics and intestinal flora profiling.…”

Section: Discussionmentioning

confidence: 99%

Dose effect of high‐docosahexaenoic acid tuna oil on dysbiosis in high‐fat diet mice

Zhang

Han

et al. 2022

J Sci Food Agric

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BACKGROUND: The health benefits of tuna oil, which is different from the fish oil commonly studied, and its higher docosahexaenoic acid (DHA) content, have attracted much scientific attention in recent years. In this study, prepared tuna oil with higher DHA (HDTO) content was employed. It was the first to integrate microbiome and metabolome from a dose-effect perspective to investigate the influence of HDTO on gut dysbiosis and metabolic disorders in diet-induced obese mice. RESULTS: Higher DHA tuna oil was effective in reversing high-fat-diet-induced metabolic disorders and altering the composition and function of gut microbiota, but these effects were not uniformly dose dependent. The flora and metabolites that were targeted to be regulated by HDTO supplementation were Prevotella, Bifidobacterium, Olsenella, glycine, L-aspartate, L-serine, L-valine, L-isoleucine, L-threonine, L-tyrosine, glyceric acid, glycerol, butanedioic acid, and citrate, respectively. Functional pathway analysis revealed that alterations in these metabolic biomarkers were associated with six main metabolic pathways: glycine, serine, and threonine metabolism; glycerolipid metabolism; glyoxylate and dicarboxylate metabolism; alanine, aspartate, and glutamate metabolism; aminoacyl-tRNA biosynthesis, and the citrate cycle (TCA cycle).CONCLUSION: Various doses of HDTO could attenuate endogenous disorders to varying degrees by regulating multiple perturbed pathways to the normal state. This explicit dose research for novel fish oil with high-DHA will provide a valuable reference for those seeking to exploit its clinical therapeutic potential.

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“…Many of the animal studies with fish oil [ 38 , 39 , 40 ] showed increased energy expenditure and/or thermogenesis and improvement in glucose and lipid metabolism with concurrent increases in thermogenic Ucp1 and/or Pgc1α expression in the BAT; however, increased energy expenditure and improvement in metabolism without significant increases in Ucp1 and/or Pgc1α expression have also been reported [ 41 ], possibly due to the differences in study designs, fish oil source and composition, and the dose and duration of the treatments. Mice studies with pure EPA showed dose-dependent increases in energy expenditure [ 42 ] and increased UCP1 protein expression at the highest dose tested [ 43 ]. However, whether the downstream epoxidized metabolites of EPA and DHA are at least partially responsible for the beneficial effects remains elusive.…”

Section: Discussionmentioning

confidence: 99%

Differential Effects of 17,18-EEQ and 19,20-EDP Combined with Soluble Epoxide Hydrolase Inhibitor t-TUCB on Diet-Induced Obesity in Mice

Yang

et al. 2021

IJMS

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17,18-Epoxyeicosatetraenoic acid (17,18-EEQ) and 19,20-epoxydocosapentaenoic acid (19,20-EDP) are bioactive epoxides produced from n-3 polyunsaturated fatty acid eicosapentaenoic acid and docosahexaenoic acid, respectively. However, these epoxides are quickly metabolized into less active diols by soluble epoxide hydrolase (sEH). We have previously demonstrated that an sEH inhibitor, t-TUCB, decreased serum triglycerides (TG) and increased lipid metabolic protein expression in the brown adipose tissue (BAT) of diet-induced obese mice. This study investigates the preventive effects of t-TUCB (T) alone or combined with 19,20-EDP (T + EDP) or 17,18-EEQ (T + EEQ) on BAT activation in the development of diet-induced obesity and metabolic disorders via osmotic minipump delivery in mice. Both T + EDP and T + EEQ groups showed significant improvement in fasting glucose, serum triglycerides, and higher core body temperature, whereas heat production was only significantly increased in the T + EEQ group. Moreover, both the T + EDP and T + EEQ groups showed less lipid accumulation in the BAT. Although UCP1 expression was not changed, PGC1α expression was increased in all three treated groups. In contrast, the expression of CPT1A and CPT1B, which are responsible for the rate-limiting step for fatty acid oxidation, was only increased in the T + EDP and T + EEQ groups. Interestingly, as a fatty acid transporter, CD36 expression was only increased in the T + EEQ group. Furthermore, both the T + EDP and T + EEQ groups showed decreased inflammatory NFκB signaling in the BAT. Our results suggest that 17,18-EEQ or 19,20-EDP combined with t-TUCB may prevent high-fat diet-induced metabolic disorders, in part through increased thermogenesis, upregulating lipid metabolic protein expression, and decreasing inflammation in the BAT.

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Discordant Dose-Dependent Metabolic Effects of Eicosapentanoic Acid in Diet-Induced Obese Mice

Cited by 15 publications

References 68 publications

Sex Differences in Early Programming by Maternal High Fat Diet Induced-Obesity and Fish Oil Supplementation in Mice

Sex Differences in Early Programming by Maternal High Fat Diet Induced-Obesity and Fish Oil Supplementation in Mice

Dose effect of high‐docosahexaenoic acid tuna oil on dysbiosis in high‐fat diet mice

Differential Effects of 17,18-EEQ and 19,20-EDP Combined with Soluble Epoxide Hydrolase Inhibitor t-TUCB on Diet-Induced Obesity in Mice

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