n-3 Dietary supplementation and lipid metabolism: Differences between vegetable- and fish-derived oils

Abstract The effect of flaxseed oil rich in linolenic acid (ALA), and a mixed oil (flaxseed oil and fish oil) rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), on the lipid clearance and peroxisome proliferator activated receptors (PPARs) in liver and adipose tissue of rats fed for 30 days with the two oils was evaluated. The results showed that after treatment with the mixed oil the hematic triacylglycerol content was significantly decreased compared to control animals. Regarding the tissue distribution of the major omega-3 fatty acids, both oils were able to increase ALA, EPA, docosapentaenoic acid (DPA) in liver and adipose tissue; and DHA solely in the adipose tissue. Finally the treatment with either flaxseed or mixed oil increased hepatic PPAR-γ expression but only the mixed oil enhanced the hepatic expression of PPAR-α. No effect on adipose tissue PPAR-γ expression was observed with both oils' treatment

Morphological and Receptorial Changes in the Epididymal Adipose Tissue of Rats Subjected to a Stressful Stimulus.

Obesity is nowadays related to other pathological conditions such as inflammation, insulin resistance, and diabetes, but little is known about the relationship between psychological stress and adipocytes. We decided to study the expression of the translocator protein (TSPO) 18-kDa, peroxisome proliferator-activated receptor-\u3b3 (PPAR-\u3b3), mitochondrial uncoupling protein-1 (UCP-1), and adipocyte morphology in the adipose tissue of rats subjected to stress conditions. In our model of stress, rats fasted for 24 h were placed in a restraint cage and then immersed vertically to the level of the xiphoid process in a water bath at 23 \ub0C for 7 h. After that period, we removed the epididymal adipose tissues for the subsequent analysis. The optical and electron microscopy revealed that adipocytes of control rats formed a continuous epithelial-like cell layer; on the contrary in the adipocytes of stressed rats some cells have merged together and the number of vessels formed seems to increase. Stressed adipocytes presented unilocular cells with numerous mitochondria with a morphology ranging between that of brown adipose tissue (BAT) and white adipose tissue (WAT). Interestingly, when we investigated the subcellular distribution of UCP-1 by immunogold electron microscopy, the adipose tissue of stressed rats was positive for UCP-1. From the immunoblot analysis with anti-PPAR-\u3b3 antibody, we observed an increased expression of PPAR-\u3b3 in the adipocytes of stressed group compared with control group (P < 0.05). Stress induced the expression of TSPO 18-kDa receptor (B(max) = 106.45 \ub1 5.87 fmol/mg proteins), which is undetectable by saturation-binding assay with [(3)H]PK 11195 in the control group

Thinning Can Reduce Losses in Carbon Use Efficiency and Carbon Stocks in Managed Forests Under Warmer Climate

Forest carbon use efficiency (CUE, the ratio of net to gross primary productivity) represents the fraction of photosynthesis that is not used for plant respiration. Although important, it is often neglected in climate change impact analyses. Here we assess the potential impact of thinning on projected carbon cycle dynamics and implications for forest CUE and its components (i.e., gross and net primary productivity and plant respiration), as well as on forest biomass production. Using a detailed process-based forest ecosystem model forced by climate outputs of five Earth System Models under four representative climate scenarios, we investigate the sensitivity of the projected future changes in the autotrophic carbon budget of three representative European forests. We focus on changes in CUE and carbon stocks as a result of warming, rising atmospheric CO2 concentration, and forest thinning. Results show that autotrophic carbon sequestration decreases with forest development, and the decrease is faster with warming and in unthinned forests. This suggests that the combined impacts of climate change and changing CO2 concentrations lead the forests to grow faster, mature earlier, and also die younger. In addition, we show that under future climate conditions, forest thinning could mitigate the decrease in CUE, increase carbon allocation into more recalcitrant woody pools, and reduce physiological-climate-induced mortality risks. Altogether, our results show that thinning can improve the efficacy of forest-based mitigation strategies and should be carefully considered within a portfolio of mitigation options

The Endocrine Disruptor Mono-(2-Ethylhexyl) Phthalate Affects the Differentiation of Human Liposarcoma Cells (SW 872)

Esters of phthalic acid (phthalates) are largely used in industrial plastics, medical devices, and pharmaceutical formulations. They are easily released from plastics into the environment and can be found in measurable levels in human fluids. Phthalates are agonists for peroxisome proliferator-activated receptors (PPARs), through which they regulate translocator protein (TSPO; 18 kDa) transcription in a tissue-specific manner. TSPO is a drug- and cholesterol-binding protein involved in mitochondrial respiration, steroid formation, and cell proliferation. TSPO has been shown to increase during differentiation and decrease during maturation in mouse adipocytes. The purpose of this study was to establish the effect of mono-(2-ethylhexyl) phthalate (MEHP) on the differentiation of human SW 872 preadipocyte cells, and examine the role of TSPO in the process. After 4 days of treatment with 10 µM MEHP, we observed changes in the transcription of acetyl-CoA carboxylase alpha, adenosine triphosphate citrate lyase, glucose transporters 1 and 4, and the S100 calcium binding protein B, all of which are markers of preadipocyte differentiation. These observed gene expression changes coincided with a decrease in cellular proliferation without affecting cellular triglyceride content. Taken together, these data suggest that MEHP exerts a differentiating effect on human preadipocytes. Interestingly, MEHP was able to temporarily increase TSPO mRNA levels through the PPAR-α and β/δ pathways. These results suggest that TSPO can be considered an important player in the differentiation process itself, or alternatively a factor whose presence is essential for adipocyte development

La supplementazione di olio di lino aumenta la concentrazione plasmatica e tissutale dell'acido linolenico e cambia l'espressione dei recettori attivanti la proliferazione dei perossisomi (PPAR)

E’ stata studiata la biodisponibilità dell’olio di lino dopo supplementazione acuta analizzando i livelli di acido linolenico (ALA), acido linoleico, EPA, DPA e DHA nel siero e nei tessuti (adiposo, epatico e cerebrale) di ratti dopo 2-4-8-16 ore dalla somministrazione. La quantità di olio di lino somministrata è stata corrispondente a 1-2,5-5 g di ALA/kg. Gli esteri metilici degli acidi grassi ottenuti mediante metilazione diretta con MeOH/HCl, sono stati quantificati mediante GC/MS (GC Varian 3400/ Finnigan MAT SSQ 710 A) ad impatto elettronico a –70 eV su colonna capillare HP-INNOWAX (30 m x 0,25 mm DI x 0,25 m).I livelli serici di ALA nel gruppo trattato con olio di lino alla dose di 1 g/kg, dopo 2h aumentano del 70% andando da 0,067 ± 0,007 a 0,096 ± 0,008 mg/mL (P<0.001 Anova, post test Bonferroni) mentre nessuna variazione significativa è stata riscontrata nel gruppo trattato con 2,5 g/kg (0,142 ± 0,009) o con 5 g/kg dopo 2 h (0,140 ± 0,008). Un aumento significativo di ALA è stato determinato nel tessuto adiposo e nel fegato dopo 4 ore dalla somministrazione di 1 g/kg mentre le dosi maggiori (2,5-5 g/kg) non producono nessun cambiamento significativo. Per quanto riguarda l’acido linoleico non è stato determinato nessun aumento significativo confermando che l’olio di lino è soprattutto una fonte di acidi grassi della serie -3.Alla luce dei risultati ottenuti dopo trattamento acuto, si è reso necessario valutare la biodisponibilità dell’olio di lino dopo trattamento cronico di un mese alla dose ottimale di 1 g di ALA/kg. In questo caso la quantificazione degli acidi grassi è stata effettuata mediante HPLC/UV con una colonna a fase inversa C18 previa derivatizzazione con p-bromofenacil bromuro [1]. Si è potuto notare un significativo incremento nel siero e nel fegato dei valori di ALA, EPA e DPA in conformità con studi precedenti [2]. Non ci sono significative variazioni dei livelli serici di colesterolo totale, HDL, LDL mentre si nota una diminuzione significativa della trigliceridemia.E’ stata inoltre valutata mediante tecnica di Western blot l’espressione dei recettori PPAR nelle due isoforme α, e γ rispettivamente nel fegato e nel tessuto adiposo dopo trattamento cronico con olio di lino.Le bande relative a PPAR e e -actina sono state quantificate e l’espressione di PPAR è stata valutata come rapporto PPAR- e /-actina.[1] Metha et al. J. Chromat. B 1998, 719: 9-23[2] Harper C.R. et al. J. Nutr. 2006, 136: 2844-2848

Endogenous benzodiazepines and intestinal bacterial flora in normal and pathological conditions

Evidence has been provided that benzodiazepine (BZD)-like substances are increased in the brains of animals with experimental HE, as well as in serum and in cerebrospinal fluid of patients with HE due to liver cirrhosis and fulminant hepatic failure. Thus, BDZ-like compounds can be regarded as precipitating factors of hepatic encephalopathy requiring the presence of a cerebral supersensitivity to these compounds. The endogenous biosynthetic pathway for the production of natural benzodiazepines has not yet been found while their presence in food has been already described. Furthermore it has been demonstrated by in vitro experiments that microorganims can synthesise molecules with BDZ structures and by in vivo studies that intestinal bacterial flora contributed by 40% to level of total natural benzodiazepines in serum of cirrhotic patients. The aim of the present study was to: 1) confirm the partial contribution of intestine to the level of circulating natural BDZ in commercial BDZ free patients, 2) to study the influence of the chronic administration of a symbiotic compound (Zyrfos-Alfa Wassermann) on the serum concentration of BDZ-like compounds in rats.The serum samples obtained by acid precipitation was chromatographed at 0.8 ml/min on a LiChrospher 100 RP-18 column (250x4.0 mm; 5 \uf06dm) equilibrated with 80% water/0.1% TFA and 20% acetonitrile. The sample was analysed using a water/0.1% TFA and acetonitrile gradient at 0.5% from 20 to 58% acetonitrile. 75 fraction were collected, lyophilised and tested for their ability to inhibit [3H]RO 15-1788 specific binding to central BDZ binding site.The concentration of BDZ-like substances in portal vein of cirrhotic patients (n=10) reach levels of 1024.24 \ub1 22.78 ng diazepam equivalent (DE)/mL in comparison with the circulating value of 162.44 \ub1 10.89 ng DE/mL. These data further demonstrate that there is a intestinal source of the above mentioned compounds. As far as regard the influence of the symbiotic which is composed by probiotic, prebiotic and B vitamins, herein we report that after 14 days of chronic administration the level of BDZ-like compounds decreased from level of 173.5 \ub1 43.76 ng DE/mL present in controls to level under the detection limit (0.5 ng DE/mL).The reported experiments and data seem to further demonstrate that the intestinal bacterial flora contribute to the amount of circulating natural BDZs both in normal and pathological conditions. Moreover it might be possible to modulate the level of these compounds by the administration of dietary supplements

Polyunsaturated fatty acid levels in rat tissues after chronic treatment with dietetic oils

BACKGROUND: The essential fatty acids can be helpful in the prevention of several pathologies. The purpose of this study was to quantify the major n-3 and n-6 fatty acids in tissues of rats fed with flaxseed oil and with a dietetic oil in order to evaluate how their chronic supplementation could influence the correspondent in vivo levels and to study the effectiveness of the dietetic oil compared to flaxseed oil. RESULTS: Fatty acids were successfully extracted from biological samples, subjected to derivatization procedure and analysed by high-performance liquid chromatography with UV detection under gradient elution mode. The developed method showed good linearity, precision and accuracy with recoveries ranging from 89% to 92%. Animals treated with flaxseed and dietetic oils showed enhanced levels of n-3 fatty acids compared to control groups, with a significant higher levels of EPA and DHA in the brain and in the adipose tissue of the dietetic groups compared to the flaxseed groups. CONCLUSION: The obtained data underline that the tested oils can effectively enhance the tissue levels of n-3 fatty acids and therefore they could be successfully used in the dietetic treatment of lipid related diseases

EFFETTI DELLA SUPPLEMENTAZIONE DIETETICA CON OLIO DI LINO SULLA SINTESI DELLE KINURENINE IN ANIMALI CON IL MORBO DI HUNTINGTON.

E\u2019 stato ipotizzato che il pathway delle kinurenine abbia un ruolo importante nel morbo di Huntington, una patologia neurodegenerativa causata dall\u2019espansione del tratto di poliglutamina della proteina huntingtina. Durante la fase iniziale della patologia, i livelli cerebrali di due metaboliti della via delle kinurenine, l\u2019acido chinolinico e il suo precursore la 3-idrossi chinurenina sono risultati elevati. Inoltre in uno studio clinico \ue8 stato dimostrato che il trattamento con acido eicosapentenoico aveva effetti benefici sulla corea e sui sintomi motori.Lo scopo della ricerca \ue8 stato quello di valutare gli effetti della supplementazione di acidi grassi della serie omega 3 nell\u2019Huntington studiando in particolare il pathway delle kinurenine.Topi transgenici con morbo di Huntington (R6/2 - HD) e topi wild-type (WT) sono stati alimentati cronicamente per un mese con olio di oliva (utilizzato come controllo) e con olio dietetico costituito da un\u2019associazione di olio di lino, ricco in acido linolenico (ALA), olio di girasole e olio di pesce ricco in acido eicosapentenoico (EPA) e docosaesanoico (DHA).Nel cervello \ue8 stato determinato un significativo aumento (p<0,05) dei livelli di ALA, EPA e DHA nel topo WT trattato con olio dietetico rispetto al corrispondente trattato col olio di oliva: lo stesso andamento \ue8 stato determinato nel topo HD trattato con olio dietetico con un aumento significativo in EPA e DHA (p<0,01). Non \ue8 stata determinata nessuna variazione nel livelli di acido linoleico e di acido arachidonico n\ue9 nei topi WT n\ue9 in quelli HD. Nei topi HD \ue8 stato determinato un minore livello di DHA (p<0,01) e un maggiore livello di acido arachidonico (p<0,01) rispetto ai topi WT. Il profilo degli acidi grassi nel tessuto adiposo riflette quello cerebrale mentre nel fegato \ue8 stato misurato un aumento significativo di EPA e DHA sia nel topo WT che nel topo HD dopo trattamento cronico con olio dietetico. EPA e DHA sono maggiori nel topo HD (p<0,001) al WT (p<0,05).Per quanto riguarda gli esperimenti sul pathway delle kinurenine, l\u20193H-kinurenina \ue8 stata iniettata nello striato e si sono misurati i metaboliti prodotti mediante analisi HPLC. Non \ue8 stata determinata alcuna variazione nelle concentrazioni di acido chinurenico, acido chinolinico e 3-idrossi chinurenina.Concludendo il trattamento dietetico con olio arricchito in acidi grassi delle serie omega 3 ha mostrato benefici nella patologia di Huntington