Hydroxytyrosol prevents reduction in liver activity of Δ-5 and Δ-6 desaturases, oxidative stress, and depletion in long chain polyunsaturated fatty acid content in different tissues of high-fat diet fed mice

Abstract

BackgroundEicosapentaenoic acid (EPA, C20:5n-3), docosahexaenoic acid (DHA, C22:6n-3) and arachidonic acid (AA, C20:4n-6) are long-chain polyunsaturated fatty acids (LCPUFAs) with relevant roles in the organism. EPA and DHA are synthesized from the precursor alpha-linolenic acid (ALA, C18:3n-3), whereas AA is produced from linoleic acid (LA, C18:2n-6) through the action of Δ5 and Δ6-desaturases. High-fat diet (HFD) decreases the activity of both desaturases and LCPUFA accretion in liver and other tissues. Hydroxytyrosol (HT), a natural antioxidant, has an important cytoprotective effects in different cells and tissues.MethodsMale mice C57BL/6 J were fed a control diet (CD) (10% fat, 20% protein, 70% carbohydrates) or a HFD (60% fat, 20% protein, 20% carbohydrates) for 12 weeks. Animals were daily supplemented with saline (CD) or 5 mg HT (HFD), and blood and the studied tissues were analyzed after the HT intervention. Parameters studied included liver histology (optical microscopy), activity of hepatic desaturases 5 and 6 (gas-liquid chromatography of methyl esters derivatives) and antioxidant enzymes (catalase, superoxide dismutase, glutathione peroxidase, and glutathione reductase by spectrophotometry), oxidative stress indicators (glutathione, thiobarbituric acid reactants, and the antioxidant capacity of plasma), gene expression assays for sterol regulatory element-binding protein 1c (SREBP-1c) (qPCR and ELISA), and LCPUFA profiles in liver, erythrocyte, brain, heart, and testicle (gas-liquid chromatography).ResultsHFD led to insulin resistance and liver steatosis associated with SREBP-1c upregulation, with enhancement in plasma and liver oxidative stress status and diminution in the synthesis and storage of n-6 and n-3 LCPUFAs in the studied tissues, compared to animals given control diet. HT supplementation significantly reduced fat accumulation in liver and plasma as well as tissue metabolic alterations induced by HFD. Furthermore, a normalization of desaturase activities, oxidative stress-related parameters, and tissue n-3 LCPUFA content was observed in HT-treated rats over control animals.ConclusionsHT supplementation prevents metabolic alterations in desaturase activities, oxidative stress status, and n-3 LCPUFA content in the liver and extrahepatic tissues of mice fed HFD.Electronic supplementary materialThe online version of this article (doi:10.1186/s12944-017-0450-5) contains supplementary material, which is available to authorized users.

Trace Elements and Fatty Acid Profile of Argyrosomus regius (Asso, 1801) from Mediterranean Aquaculture

“…Estimated monthly intakes (EMI) in μg/week/70 kg body weight is followed by an asterisk (* previously for the European sea bass [10,69,70]. Although significant amounts of MUFA and SFA were found, PUFA were the main fraction in all samples, suggesting that SFA and MUFA could promote the improvement of PUFA muscle deposition [71]. These results agree with those from [17].…”

Docosahexaenoic acid and hydroxytyrosol co‐administration fully prevents liver steatosis and related parameters in mice subjected to high‐fat diet: A molecular approach

“…Second, the protective effects of HT in liver injury models are primarily related to its polyphenolic structure, which confers its free‐radical scavenging and metal chelating properties, therefore lowering free‐radical levels and oxidative stress status (Figure ), with the concomitant increase the antioxidant potential of the liver (Figure 5). Consequently, HT may favor FAO over de novo lipogenesis through maintenance of the basal level of n‐ 3 LCPUFAs that supports PPAR‐α (Figure ) over SREBP‐1c (Figure ) functioning. Additional effects associated with the beneficial action of HT in HFD‐induced liver steatosis include (a) recovery of the activity of Δ5‐ and Δ6‐desaturases supporting n‐3 LCPUFA repletion; and (b) normalization of the protein levels of SREBP‐1c and FAS enhanced by HFD .…”

“…Consequently, HT may favor FAO over de novo lipogenesis through maintenance of the basal level of n‐ 3 LCPUFAs that supports PPAR‐α (Figure ) over SREBP‐1c (Figure ) functioning. Additional effects associated with the beneficial action of HT in HFD‐induced liver steatosis include (a) recovery of the activity of Δ5‐ and Δ6‐desaturases supporting n‐3 LCPUFA repletion; and (b) normalization of the protein levels of SREBP‐1c and FAS enhanced by HFD . Collectively, data presented suggest that the co‐administration of DHA and HT completely prevents HFD‐induced liver steatosis by mechanisms leading to suppression of the changes elicited in oxidative stress, de novo lipogenesis and FAO, which normalize the hepatic SREBP‐1c/PPAR‐α ratio drastically enhanced by HFD (Figure g).…”

Protective Effects of Eicosapentaenoic Acid Plus Hydroxytyrosol Supplementation Against White Adipose Tissue Abnormalities in Mice Fed a High-Fat Diet

“…The methodology used to assess phospholipid fatty acid composition was described elsewhere [ 13 , 24 ]. Briefly, the total lipids from EWAT were extracted with chloroform/methanol (2:1 v/v ) according to the method proposed by Bligh and Dyer [ 25 ].…”