Fatty Acid-rich Diet Research Articles

Risk Factors for Dry Eye Syndrome: A Retrospective Case-Control Study.

To investigate the independent risk factors of dry eye syndrome (DES) in Chinese. A hospital-based age- and sex-matched population was enrolled with a case-control ratio of 1:2, with 789 DES case patients and 1119 healthy family members. Both groups underwent standard ophthalmologic examinations, including slit-lamp evaluation of the anterior segment, measurement of tear film breakup time, Schirmer test, and corneal fluorescein staining. Data on demographic characteristics and lifestyle habits were collected using a questionnaire. Dry eye syndrome risk factors were identified by univariate and multivariate logistic regression analyses. The following independent risk factors showed significant association with DES: diabetes (odds ratio [OR], 1.408; 95% confidence interval [CI], 1.031 to 1.924), hepatitis C (OR, 3.326; 95% CI, 1.632 to 6.776); connective tissue disease (OR, 2.157; 95% CI, 1.679 to 2.771), benign prostatic hyperplasia (OR, 3.892; 95% CI, 2.476 to 6.116), rosacea (OR, 3.747; 95% CI, 1.972 to 7.120), posttraumatic stress disorder (OR, 1.449; 95% CI, 1.043 to 2.013), hematopoietic stem cell transplantation (OR, 7.269; 95% CI, 2.312 to 22.849), head and neck radiotherapy (OR, 8.776; 95% CI, 3.096 to 24.873), postmenopausal estrogen therapy (OR, 1.912; 95% CI, 1.160 to 3.151), antihistamines (OR, 2.040; 95% CI, 1.516 to 2.746), antidepressants (OR, 1.982; 95% CI, 1.077 to 3.647), contact lenses (OR, 2.366; 95% CI, 1.266 to 4.423), and video display terminal exposure for more than 6 h/d (OR, 2.275; 95% CI, 1.451 to 3.568). Potentially protective factors against DES were vitamin supplements (OR, 0.716; 95% CI, 0.528 to 0.972) and Ω-3 fatty acid-rich diet (OR, 0.514; 95% CI, 0.332 to 0.796). Several known risk factors of DES are applicable to Chinese, and some distinctive dietary factors may be protective in this population.

Coenzyme Q Protects Against Age-Related Alveolar Bone Loss Associated to n-6 Polyunsaturated Fatty Acid Rich-Diets by Modulating Mitochondrial Mechanisms.

An age-dependent model of the periodontium was reproduced to evaluate the effect of life-long feeding on a low coenzyme Q10 dosage in n-6, n-3 polyunsaturated fatty acid or monounsaturated fatty acid-based diets on periodontal tissues of young and old rats. Results shown that exacerbated age-related alveolar bone loss previously associated to n-6 polyunsaturated fatty acid diet was attenuated by coenzyme Q10 Gene expression analysis suggests that involved mechanisms might be related to a restored capacity of mitochondria to adapt to aging in gingival cells from rats fed on n-6 polyunsaturated fatty acid. In particular, this could be due to an age-related increase of the rate of mitochondrial biogenesis and a better oxidative and respiratory balance in these animals. From the nutritional and clinical point of view, it is noteworthy that supplementation with coenzyme Q10 could counteract the negative effects of n-6 polyunsaturated fatty acid on alveolar bone loss (a major feature of periodontitis) associated to age.

Monounsaturated fatty acids-rich diets in hypercholesterolemic-growing rats

The effects of replacing dietary saturated fat by different monounsaturated fatty acid (ω-9MUFA) sources on serum lipids, body fat and bone in growing hypercholesterolemic rats were studied. Rats received one of the six different diets: AIN-93G (control, C); extra virgin olive oil (OO) + C; high-oleic sunflower oil (HOSO) + C or atherogenic diet (AT) for 8 weeks; the remaining two groups received AT for 3 weeks and then, the saturated fat was replaced by an oil mixture of soybean oil added with OO or HOSO for 5 weeks. Rats consuming MUFA-rich diets showed the highest body fat, hepatic index and epididymal, intestinal and perirenal fat, and triglycerides. T-chol and non-HDL-chol were increased in HOSO rats but decreased in OO rats. Bone mineral content and density were higher in both OO and HOSO groups than in AT rats. This study casts caution to the generalization of the benefits of MUFA for the treatment of hypercholesterolemia.

Docosahexaenoic acid, G protein–coupled receptors, and melanoma: is G protein–coupled receptor 40 a potential therapeutic target?

BackgroundTo determine the effect of docosahexaenoic acid (DHA) on the growth of human melanoma in vitro and in vivo and to better understand the potential role of the G protein–coupled receptors (GPRs) in mediating this effect. Materials and methodsFor in vitro studies, human melanoma and control fibroblast cells were treated with DHA and TAK-875 (selective GPR40 agonist) and a cell viability assay was performed to determine cell counts. A murine subcutaneous xenograft model of human melanoma was used to test the effect of dietary treatment with an omega-3 fatty acid (FA) rich diet compared with an omega-6 FA rich diet on the growth of human melanoma in vivo. A similar animal model was used to test the effect of oral TAK-875 on the growth of established melanoma tumors in vivo. ResultsDHA has an inhibitory effect on the growth of human melanoma both in vitro and in vivo. Tumors from animals on the omega-3 FA rich diet were 69% smaller in weight (P = 0.005) and 76% smaller in volume compared with tumors from animals on the omega-6 FA rich diet. TAK-875 has an inhibitory effect on the growth of human melanoma both in vitro and in vivo. Tumors from animals treated with TAK-875 were 46% smaller in weight (P = 0.07), 62% smaller in volume (P = 0.03), and grew 77% slower (P = 0.04) compared with the placebo group. ConclusionsDHA and TAK-875 have a profound and selective inhibitory effect on the growth of human melanoma both in vitro and in vivo.

Abstract A31: Omega-3 fatty acids may regulate levels of pAkt through a mechanism independent of PI3K

Abstract The effects of dietary factors on pancreatic cancer have been proposed to augment etiology of disease, yet the mechanisms involved are poorly understood. Our previous work demonstrated that omega-6 fatty acid rich diets have been associated with increased severity of pancreatic neoplasia, but conversely, omega-3 fatty acid rich diets have chemoprotective effects against Kras-induced pancreatic neoplasia. Also, our more recent data indicates that docosahexaenoic acid (DHA, omega-3 fatty acid) and linoleic acid (LA, omega-6 fatty acid) have opposing effects on protein kinase B (Akt)-mediated mitogenic signaling in Human Pancreatic Duct Epithelial cells in vitro. Furthermore, published studies suggest that one mechanism of action may be through cyclooxygenase (COX)-2 derived prostaglandin E2 (PGE2) secretion leading to cell proliferation. In our current work, we demonstrate that DHA treated HPDE cells do not generate a change in phosphorylated Akt (pAkt) levels and proliferation between cells with or without COX-2 inhibition. As a major maker of proliferation, Akt is often activated by phosphatidylinositol 3 kinase (PI3K), which facilitates conversion of phosphatidylinositol bisphosphate (PIP2) to phosphatidylinositol trisphosphate (PIP3), and PIP3 phosphorylates Akt. Yet the effects of DHA are not directly at the level of PI3K, as HPDE cells treated with a PI3K inhibitor (LY294002), a significantly further reduction in DHA-induced decrease of pAkt. Therefore, it is likely that DHA may not mediate pAkt through PI3K, and we propose that due to its high lipid solubility, DHA may interact with membrane-tethered targets including PIP2. Citation Format: Lingji Zhu, Windel Emman T. Marsacarinas, Daniel R. Principe, Paul J. Grippo. Omega-3 fatty acids may regulate levels of pAkt through a mechanism independent of PI3K. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr A31.

Postprandial Activation of P53-Dependent DNA Repair Is Modified by Mediterranean Diet Supplemented With Coenzyme Q10 in Elderly Subjects

Alterations in the expression levels of genes and proteins involved in oxidative stress and DNA damage response underlie the phenotypic changes associated with aging. We have investigated whether the quality of dietary fat alters postprandial gene expression and protein levels involved in p53-dependent DNA repair and whether the supplementation with Coenzyme Q10 improves this situation in an elderly population. Twenty participants were randomized to receive three isocaloric diets each for 4 weeks: Mediterranean diet supplemented with Coenzyme Q10, Mediterranean diet, saturated fatty acid-rich diet. After a 12-hour fast, volunteers consumed a breakfast with a fat composition similar to that consumed in each of the diets. Gadd45a, Gadd45b, OGG1, APE-1/Ref-1, DNApolβ, and XPC gene expression and nuclear Gadd45a, APE-1/Ref-1, and DNApolβ protein levels were determined in peripheral blood mononuclear cells. Mediterranean diet and Mediterranean diet supplemented with Coenzyme Q10diets downregulated Gadd45a protein levels compared with the saturated fatty acid-rich diet. Moreover, Mediterranean diet supplemented with Coenzyme Q10diet evoked lower postprandial Gadd45a, Gadd45b, XPC, DNApolβ and OGG1 gene expression and lower APE-1/Ref-1 and DNApolβ protein levels than the saturated fatty acid-rich diet. Our results support a beneficial effect of Mediterranean diet and Mediterranean diet supplemented with Coenzyme Q10 on DNA damage as compared to the detrimental action of a saturated fatty acid-rich diet, which triggers the p53-dependent DNA repair machinery.

Energy-restricted, n-3 polyunsaturated fatty acids-rich diet improves the clinical response to immuno-modulating drugs in obese patients with plaque-type psoriasis: a randomized control clinical trial

Low-grade systemic inflammation associated with obesity may worsen the clinical course of psoriasis. This study aimed to assess the effectiveness of an energy-restricted diet, enriched in n-3 polyunsaturated fatty acids (PUFAs) and poor in n-6 PUFAs, on metabolic markers and clinical outcome of obese patients with psoriasis. Forty-four obese patients with mild-to-severe plaque-type psoriasis treated with immuno-suppressive drugs were randomized to assume for six months either their usual diet or an energy-restricted diet (20 kcal/kg/ideal body weight/day) enriched of n-3 PUFAs (average 2.6 g/d). All patients continued their immuno-modulating therapy throughout the study. At 3 and 6 months, a significant clinical improvement was observed in patients assuming the low-calorie high n-3 PUFAs diet respect to controls. Specifically Psoriasis Area Score Index (7.7 ± 3.7, 5.3 ± 4.3 and 2.6 ± 3.0, respectively; p < 0.05), itch scores (15.4 ± 13.5, 12.3 ± 12.1 and 1.8 ± 5.9, respectively; p < 0.05) and Dermatological Life Quality Index (19.5 ± 1.9, 11.4 ± 3.5 and 5.1 ± 1.6; respectively, p < 0.05) all decreased respect to baseline. In these subjects but not in controls, a significant decrease in body weight (93.8 ± 10.1, 85.8 ± 11.4 and 83.1 ± 12.1 kg, respectively; p < 0.05), waist circumference (112.7 ± 7.2, 106.1 ± 10.3 and 101.9 ± 10.4 cm; p < 0.05), serum triglycerides (141.8 ± 51.1, 100.5 ± 26.6 and 90.2 ± 34.5 mg/dL; respectively, p < 0.05), serum total cholesterol (198.3 ± 31.7, 171.4 ± 29.0 and 176.5 ± 20.5 mg/dL; respectively, p < 0.05) and n-6/n-3 ratio intake also occurred (5.1 ± 0.9, 2.0 ± 0.9 and 2.3 ± 1.1; respectively, p < 0.05). In obese psoriatic patients, an energy-restricted diet designed to increase n-3 and reduce n-6 PUFAs, ameliorated the metabolic profile and, by increasing the response to immuno-modulating therapy, improved the clinical outcomes of the disease (ClinicalTrials.gov identifier: NCT01876875).

The long-term ingestion of a diet high in extra virgin olive oil produces obesity and insulin resistance but protects endothelial function in rats: a preliminary study

BackgroundIt has been hypothesized that fatty acids derived from a diet high in saturated fat may negatively affect endothelial function more significantly than a diet high in unsaturated fat; nevertheless, the effects of the long-term ingestion of monounsaturated fatty acids on endothelial function have been poorly studied.MethodsTo examine the chronic effects of monounsaturated (e.g., extra virgin olive oil (EVOO)) or saturated (e.g., margarine (M)) fatty acid-rich diets on the development of insulin resistance and endothelial dysfunction in rats, three groups of rats were fed control, high-EVOO or high-M diets for 20 weeks. Body weight, energy consumption, insulin resistance, lipid peroxidation and in vitro vascular reactivity with and without metformin were assessed during the study period.ResultsBoth high-fat diets produced obesity and insulin resistance. EVOO-fed rats showed smaller increases in total cholesterol and arterial lipid peroxidation when compared with M-fed rats. Vascular reactivity to phenylephrine and sodium nitroprusside was not modified, but the vasodilating effect of carbachol was especially reduced in the M-fed rats compared with the EVOO-fed or control groups. Metformin addition to the incubation media decreased the vascular response to phenylephrine; decrease that was lower in rats fed with both high fat diets, and increased the carbachol and nitroprusside effects, but the metformin-enhanced response to carbachol was lower in the M group.ConclusionsOur results suggest that feeding rats with high quantities of EVOO, despite producing obesity and insulin resistance, produces low levels of circulating cholesterol and arterial lipoperoxidation compared to M fed rats and shows a preserved endothelial response to carbachol, effect that is significantly enhanced by metformin only in rats fed with control and EVOO diets.

Effects of long-term administration of saturated andn-3 fatty acid-rich diets on lipid utilisation and oxidative stress in rat liver and muscle tissues

The incidence of metabolic syndrome components including obesity, lipid deregulation, insulin resistance (IR) and non-alcoholic fatty liver disease is increasing rapidly in wealthy societies. The present study was designed to determine the effect of different nutritional lipid patterns (quantity and quality) on lipid utilisation and oxidative stress in the liver and muscle of rats in an integrated fashion. A total of forty-eight Wistar male rats were fed for 12 weeks with a mixed, lard or fish-oil diet, containing either 50 or 300 g lipid/kg. Rats developed liver steatosis associated with moderate liver injury when fed the 30% lipid diets, in spite of the absence of overt obesity or IR, except when fed the lard 30% lipid diet. The intake of the 30% lipid diets decreased hepatic lipogenesis and mitochondriogenesis and increased lipid peroxidation and protein oxidation. Surprisingly, muscle lipid content was not modified whatever the administered diet. The intake of the 30% lipid diets increased the muscle protein expression of fatty acid (FA) translocase/cluster of differentiation 36 (FAT/CD36), PPARg co-activator 1a (PGC-1a) and muscle carnitine palmitoyltransferase 1 (m-CPT1), reflecting increased FA transport in the muscle associated with increased oxidative metabolism. The lard 30% lipid diet led to IR without modifying the muscle lipid content. The fish-oil 30% lipid diet failed to prevent the development of hepatic steatosis and made the tissues more prone to oxidation. Overall, the present study suggests that the FA composition of muscle is more important than lipid accumulation itself in the modulation of insulin sensitivity, and indicates that precaution should be taken when advising an unphysiologically high (pharmacological) supplementation with long-chain n-3 PUFA.

Endothelial Acyl-CoA Synthetase 1 Is Not Required for Inflammatory and Apoptotic Effects of a Saturated Fatty Acid-Rich Environment

Saturated fatty acids, such as palmitic and stearic acid, cause detrimental effects in endothelial cells and have been suggested to contribute to macrophage accumulation in adipose tissue and the vascular wall, in states of obesity and insulin resistance. Long-chain fatty acids are believed to require conversion into acyl-CoA derivatives to exert most of their detrimental effects, a reaction catalyzed by acyl-CoA synthetases (ACSLs). The objective of this study was to investigate the role of ACSL1, an ACSL isoform previously shown to mediate inflammatory effects in myeloid cells, in regulating endothelial cell responses to a saturated fatty acid-rich environment in vitro and in vivo. Saturated fatty acids caused increased inflammatory activation, endoplasmic reticulum stress, and apoptosis in mouse microvascular endothelial cells. Forced ACSL1 overexpression exacerbated the effects of saturated fatty acids on apoptosis and endoplasmic reticulum stress. However, endothelial ACSL1 deficiency did not protect against the effects of saturated fatty acids in vitro, nor did it protect insulin-resistant mice fed a saturated fatty acid-rich diet from macrophage adipose tissue accumulation or increased aortic adhesion molecule expression. Endothelial ACSL1 is not required for inflammatory and apoptotic effects of a saturated fatty acid-rich environment.

The effects of alpha lipoic acid on liver cells damages and apoptosis induced by polyunsaturated fatty acids

We studied the effect of alpha-lipoic acid (ALA) on the liver cell damages and apoptosis by n-6 polyunsaturated fatty acids (PUFA) rich diet in young rats. 24 Wistar rats were divided into four groups. During the study, 12 of them (control) were fed with standard chow and other 12 (n-6) were fed with the food containing high-fat n-6 for 8weeks. At the end of the fourth week, control and n-6 groups were randomly divided into two groups and then, 4weeks, 35mg/kg ALA are injected. Groups; control, control+ALA, n-6, n-6+ALA. The liver tissue glutathione (GSH) activity was determined. Immunohistochemistry for caspase-3 and TUNEL method for apoptosis were performed. The GSH levels have significantly decreased (p<0,001), and vacuolization in the hepatocytes, infiltration and the collagen accumulation around the central vein, hepatic stellate cells in the sinusoids have increased in n-6 group compared with the other groups. TUNEL (p<0,001) and caspase-3 (p<0,001) positive cells increased in n-6 group whereas all degenerative observations decreased in n-6+ALA group. Our results demonstrate that the feeding with n-6 PUFA causes fatty liver, fibrosis development, inflammations and apoptosis in the liver of young rats. ALA has a beneficial effects on these degenerative effects.

Abstract 19596: Endothelial Acyl-CoA Synthetase 1 is not Required for Saturated Fatty Acid- Mediated Inflammatory and Apoptotic Effects

Saturated fatty acids, such as palmitic (C16:0) and stearic acid (C18:0), cause detrimental effects in endothelial cells (ECs) that might contribute to macrophage accumulation in adipose tissue and the vascular wall in states of obesity and insulin resistance. Fatty acids require conversion into acyl-CoA derivatives to exert most biological effects, a reaction catalyzed by acyl-CoA synthetases (ACSL). We hypothesized that endothelial deficiency of ACSL1, an ACSL isoform mediating inflammatory effects in myeloid cells, would protect from detrimental effects of saturated fatty acids in vitro and saturated fat feeding in vivo. Mouse microvascular CD45-negative-CD31-positive endothelial cells (MMECs) were isolated from lungs or hearts by fluorescence activated cell sorting. In these cells and in bovine aortic ECs (BAECs), saturated fatty acids caused JNK activation, ER stress, and apoptosis, along with increased inflammatory activation, as measured by an increase in the release of the soluble adhesion molecules sICAM-1 (p&lt;0.01), and sVCAM-1 (p&lt;0.01), as well as release of the chemokine CCL2 (p&lt;0.05). In order to evaluate the role of endogenous ACSL1 in ECs, a conditional endothelial Acsl1-deficient mouse model was generated. Acsl1-deficient MMECs had significantly decreased beta-oxidation as measured by decreased acid soluble metabolite production (WT 393.1 ± 25.6, KO 270.5 ± 16.3 cpm/µg protein; p&lt;0.05). However, conditional endothelial ACSL1-deficiency did not protect against the inflammatory or apoptotic effects of saturated fatty acids in vitro, nor did it protect insulin resistant mice fed a saturated fatty acid-rich diet from epididymal adipose tissue accumulation of macrophages or increased aortic adhesion molecule expression. Conversely, forced Acsl1 overexpression in BAECs exacerbated the effects of saturated fatty acids on apoptosis and ER stress, in part through increased JNK activation. In conclusion, forced overexpression of Acsl1 can exacerbate some effects of saturated fatty acids; however, endogenous ACSL1 is not required for pro-inflammatory or pro-apoptotic responses of ECs to saturated fatty acids.

Diurnal feeding in young rats fed saturated fatty acid-rich diet

This study investigated eating pattern in weaning female Sprague-Dawley rats fed high-fat diets of varying fatty acid composition. Rats were randomly assigned to canola- or butter-based diets, and their eating pattern and body weight were assessed at early exposure (P1) and following 3 weeks (P2). In P2, a lower 24-h intake, smaller meal size, and shorter nocturnal meal duration were found in both dietary groups. In both groups, 24-h intakes were comparable throughout the experiment; however, butter-fed rats gained more weight. With canola feeding, P1 nocturnal intake was greater than diurnal intake, but intakes were comparable in P2. Butter-fed rats had similar diurnal and nocturnal intakes in P1; in P2, diurnal was greater than nocturnal intake. Canola-fed rats had similar diurnal and nocturnal meal size and eating rate, whereas butter-fed rats ate larger meals at a higher rate in the light than in the dark phase. The present work brings new knowledge about exposure to high-fat diets early in life and later development of obesity.

Nutrient and the Mind-Body Axis, in Relation to Omega-3 Fatty Acids and Amino Acids

Noncommunicable Diseases (NCDs); obesity, type 2 diabetes mellitus, Cardiovascular Diseases (CVDs) and cancer have become major health problems in both developing and developed countries. Physical inactivity and increased intake of energy rich proinflammatory foods in association with genetic predisposition are common primary risk factors for these problems. Mind-body interactions and mechanisms in relation to hypothalamus neurotransmitters and vagus nerve have been discovered in causing NCDs. Apart from above risk factors. The role of salivary glands, liver and beta cells of pancreas and their interactions with hypothalamus and vagus nerve are important mechanisms to explain the neural and behavioural factors in the pathogenesis of NCDs. In this connection, the role of w-6/w-3 fatty acids ratio as well as essential and nonessential amino acids like glutamate, arginine and cysteine (the latter two being conditionally essential in some situations) and the sulphonic acid taurine have on brain function appears to be of great interest. This broad hypothesis focusses on the role of environment on mind-body connection in the pathogenesis of NCDs. Omega-3 fatty acids and amino acids possibly glutamate, can also improve neuronal efficiency causing improvement in taste, appetite, attention, cognitive performance and mood state. Omega-3 fatty acids can improve the electroencephalographic alpha and theta oscillations which are indicators of memory function. Treatment of NCDs; coronary atherosclerosis, hypertension and type 2 diabetes with an w-3 fatty acid rich Mediterranean diet may be protective, as it is also rich in amino acids. There is a need to study the role of amino acids, especially, glutamate in the pathogenesis of NCDs, because other ‘amino’ acids like arginine, taurine and cystiene have been found to be protective against cardiovascular diseases.

Osteoarthritis in the cat: 2. how should it be managed and treated?

Osteoarthritis (OA) is very common in the cat and in many cases is associated with significant long-term pain, which limits mobility and activity, and severely compromises the animal's quality of life. The treatment of chronic arthritic pain is a major challenge and many analgesic drugs used in other species are not licensed, not available or not tested for use in the cat. Many older cats with painful OA have some degree of chronic kidney disease (CKD) and many clinicians are reluctant to use non-steroidal anti-inflammatory drugs (NSAIDs) in these animals because of the potential for nephrotoxicity. There are several publications that show that meloxicam is an effective NSAID for the cat and can be used long-term. It is easy to administer and there is published evidence that meloxicam can actually slow the progression of CKD in this species. Many other drugs are used to treat chronic pain in the cat but there is no documented evidence of their efficacy in OA. Unlike the dog, there is limited evidence for the effectiveness of omega-3 fatty acid-rich diets in managing feline OA and further work is required. There is no published data as yet for the usefulness or otherwise of nutraceuticals (glucosamine and chondroitin) in managing feline OA; studies in the authors' clinic suggest some pain-relieving effect. Research into environmental enrichment as a way of improving quality of life in cats with painful OA is lacking, but it is an approach worth using where possible. Modifications to the environment (eg, provision of comfortable bedding and ramps) are also important.

Postprandial antioxidant gene expression is modified by Mediterranean diet supplemented with coenzyme Q10 in elderly men and women

Postprandial oxidative stress is characterized by an increased susceptibility of the organism towards oxidative damage after consumption of a meal rich in lipids and/or carbohydrates. We have investigated whether the quality of dietary fat alters postprandial gene expression and protein levels involved in oxidative stress and whether the supplementation with coenzyme Q(10) (CoQ) improves this situation in an elderly population. Twenty participants were randomized to receive three isocaloric diets each for 4weeks: Mediterranean diet supplemented with CoQ (Med + CoQ diet), Mediterranean diet (Med diet), saturated fatty acid-rich diet (SFA diet). After 12-h fast, volunteers consumed a breakfast with a fat composition similar to that consumed in each of the diets. Nrf2, p22(phox) and p47(phox), superoxide dismutase 1 and 2 (SOD1 and SOD2), glutathione peroxidase 1 (GPx1), thiorredoxin reductase (TrxR) gene expression and Kelch-like ECH associating protein 1 (Keap-1) and citoplasmic and nuclear Nrf2 protein levels were determined. Med and Med + CoQ diets induced lower Nrf2, p22(phox), p47(phox), SOD1, SOD2 and TrxR gene expression and higher cytoplasmic Nrf2 and Keap-1 protein levels compared to the SFA diet. Moreover, Med + CoQ diet produced lower postprandial Nrf2 gene expression and lower nuclear Nrf2 protein levels compared to the other diets and lower GPx1 gene expression than the SFA diet. Our results support the antioxidant effect of a Med diet and that exogenous CoQ supplementation has a protective effects against free radical overgeneration through the lowering of postprandial oxidative stress modifying the postprandial antioxidant protein levels and reducing the postprandial expression of antioxidant genes in peripheral blood mononuclear cells.

Mediterranean Diet Supplemented With Coenzyme Q10 Modifies the Expression of Proinflammatory and Endoplasmic Reticulum Stress–Related Genes in Elderly Men and Women

We have investigated whether the quality of dietary fat and supplementation with coenzyme Q(10) (CoQ) modifies expression of genes related with inflammatory response and endoplasmic reticulum stress in elderly persons. Twenty participants received three diets for 4 weeks each: Mediterranean diet + CoQ (Med + CoQ), Mediterranean diet (Med), and saturated fatty acid-rich diet (SFA). After 12-hour fast, volunteers consumed a breakfast with a fat composition similar to that consumed in each of the diets. Med and Med + CoQ diets produced a lower fasting calreticulin, IL-1b, and JNK-1 gene expression; a lower postprandial p65, IKK-b, MMP-9, IL-1b, JNK-1, sXBP-1, and BiP/Grp78 gene expression; and a higher postprandial IkB-a gene expression compared with the SFA diet. Med + CoQ diet produced a lower postprandial decrease p65 and IKK-b gene expression compared with the other diets. Our results support the anti-inflammatory effect of Med diet and that exogenous CoQ supplementation in synergy with a Med diet modulates the inflammatory response and endoplasmic reticulum stress.

Ischemic Preconditioning-Like Effect of Polyunsaturated Fatty Acid-Rich Diet on Hepatic Ischemia/Reperfusion Injury

AimThe aim of this study was to investigate a possible preconditioning effect of oral diet enriched with polyunsaturated fatty acids (PUFAs) on liver ischemia/reperfusion (I/R) injuries. MethodsWistar male rats were fed a standard diet or polyunsaturated fatty acid-rich diet (PRD) enriched with (GII) or without (GIII) ω-3 PUFA. Rats were submitted to partial liver ischemia during 1 h and evaluated in pre- and post-I/R conditions. In pre-I/R condition, livers were collected for determination of fatty acid composition, liver mitochondrial function, malondialdehyde (MDA) content, and histological analysis. Four hours after liver reperfusion serum activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), serum levels of tumor necrosis factor-alpha, interleukin-6, interleukin-10, and prostaglandin-E2, liver mitochondrial function, MDA content, and histology were evaluated. ResultsIn the pre-I/R condition, GII and GIII groups had an increase on PUFA content and exhibited slight increased macrosteatosis and microsteatosis in the liver. After 4 h of reperfusion, PRD-fed rats showed a marked decrease on steatosis, diminished necrosis, an increase in MDA formation, and mitochondrial uncoupling. We also observed a marked decrease in plasma levels of cytokines and ALT and AST activities in post-I/R condition in PRD groups. ConclusionIn this experimental model in the rat, PRD has a preconditioning effect protecting the liver from I/R injury and should be object of future clinical studies.

Antimicrobial-Sensing Proteins in Obesity and Type 2 Diabetes

Obesity is well known to be associated with a cluster of metabolic diseases such as dyslipidemia, hypertension, insulin resistance, type 2 diabetes, and atherosclerosis (1). Alterations of the innate immune system are increasingly recognized to be intrinsically linked to metabolic pathways in humans (2). Central to metabolic diseases is insulin resistance associated with a low-grade inflammatory status (3). The mechanisms through which proinflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1α, interact with cellular insulin signal transduction cascades have been better understood in the last few years (4–6). In vivo, a direct correlation between increased circulating proinflammatory cytokines and insulin resistance has been well demonstrated (3,7). The origin of this increased inflammatory activity in obesity and type 2 diabetes is virtually unknown. Immune system homeostasis is challenged by continuous external insults, such as saturated fatty acid–rich diets (8), pathogen-associated molecular patterns like lipopolysaccharide (LPS) (9), advanced glycation end products (AGEs) (10), burden of infection (11), and oxidative stress (12). These continuous insults could result in a chronic low level of inflammation associated with insulin resistance. Here, we review the potential significance of neutrophil dysfunction in subjects with type 2 diabetes and the consequence of altered antimicrobial-sensing protein profile in obesity-related metabolic disturbances. Given that 60–70% of blood leukocytes are granulocytes and over 90% of granulocytes are neutrophils, polymorphonuclear cells (PMNs) are the largest fraction of white blood cells. PMNs possess a variety of functions, including chemotaxis, adhesion to the endothelium and foreign agents, phagocytosis, and microbicidal activity. PMNs are able to penetrate and migrate into infected tissues and destroy invading microorganisms after internalization by producing multiple toxic agents such as reactive oxygen species (ROS), proteases (elastase), and proteins interfering with bacterial development. Chronic disease (such as type 2 diabetes), age-associated insulin resistance, nutrition, …

Mediterranean diet supplemented with coenzyme Q10 induces postprandial changes in p53 in response to oxidative DNA damage in elderly subjects

Coenzyme Q10 (CoQ) is a powerful antioxidant that reduces oxidative stress. We explored whether the quality of dietary fat alters postprandial oxidative DNA damage and whether supplementation with CoQ improves antioxidant capacity by modifying the activation/stabilization of p53 in elderly subjects. In this crossover study, 20 subjects were randomly assigned to receive three isocaloric diets during 4 weeks each: (1) Mediterranean diet (Med diet), (2) Mediterranean diet supplemented with CoQ (Med+CoQ diet), and (3) saturated fatty acid-rich diet (SFA diet). Levels of mRNAs were determined for p53, p21, p53R2, and mdm2. Protein levels of p53, phosphorylated p53 (Ser20), and monoubiquitinated p53 were also measured, both in cytoplasm and nucleus. The extent of DNA damage was measured as plasma 8-OHdG. SFA diet displayed higher postprandial 8-OHdG concentrations, p53 mRNA and monoubiquitinated p53, and lower postprandial Mdm2 mRNA levels compared with Med and Med+CoQ diets (p < 0.05). Moreover, Med+CoQ diet induced a postprandial decrease of cytoplasmatic p53, nuclear p-p53 (Ser20), and nuclear and cytoplasmatic monoubiquitinated p53 protein (p < 0.05). In conclusion, Med+CoQ diet improves oxidative DNA damage in elderly subjects and reduces processes of cellular oxidation. Our results suggest a starting point for the prevention of oxidative processes associated with aging.