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BACKGROUND - The Transient Receptor Potential (TRP) ion channel TRPA1 is a key player in pain pathways. Irritant chemicals activate ion channel TRPA1 via covalent modification of N-terminal cysteines. We and others have shown that 15-Deoxy-Δ12, 14-prostaglandin J2 (15d-PGJ2) similarly activates TRPA1 and causes channel-dependent nociception. Paradoxically, 15d-PGJ2 can also be anti-nociceptive in several pain models. Here we hypothesized that activation and subsequent desensitization of TRPA1 in dorsal root ganglion (DRG) neurons underlies the anti-nociceptive property of 15d-PGJ2. To investigate this, we utilized a battery of behavioral assays and intracellular Ca2+ imaging in DRG neurons to test if pre-treatment with 15d-PGJ2 inhibited TRPA1 to subsequent stimulation.
RESULTS - Intraplantar pre-injection of 15d-PGJ2, in contrast to mustard oil (AITC), attenuated acute nocifensive responses to subsequent injections of 15d-PGJ2 and AITC, but not capsaicin (CAP). Intraplantar 15d-PGJ2-administered after the induction of inflammation-reduced mechanical hypersensitivity in the Complete Freund's Adjuvant (CFA) model for up to 2 h post-injection. The 15d-PGJ2-mediated reduction in mechanical hypersensitivity is dependent on TRPA1, as this effect was absent in TRPA1 knockout mice. Ca2+ imaging studies of DRG neurons demonstrated that 15d-PGJ2 pre-exposure reduced the magnitude and number of neuronal responses to AITC, but not CAP. AITC responses were not reduced when neurons were pre-exposed to 15d-PGJ2 combined with HC-030031 (TRPA1 antagonist), demonstrating that inhibitory effects of 15d-PGJ2 depend on TRPA1 activation. Single daily doses of 15d-PGJ2, administered during the course of 4 days in the CFA model, effectively reversed mechanical hypersensitivity without apparent tolerance or toxicity.
CONCLUSIONS - Taken together, our data support the hypothesis that 15d-PGJ2 induces activation followed by persistent inhibition of TRPA1 channels in DRG sensory neurons in vitro and in vivo. Moreover, we demonstrate novel evidence that 15d-PGJ2 is analgesic in mouse models of pain via a TRPA1-dependent mechanism. Collectively, our studies support that TRPA1 agonists may be useful as pain therapeutics.
Pomegranate seed oil (PSO), which is the major source of conjugated linolenic acids such as punicic acid (PuA), exhibits strong anti-inflammatory properties. Necrotizing enterocolitis (NEC) is a devastating disease associated with severe and excessive intestinal inflammation. The aim of this study was to evaluate the effects of orally administered PSO on the development of NEC, intestinal epithelial proliferation, and cytokine regulation in a rat model of NEC. Premature rats were divided into three groups: dam fed (DF), formula-fed rats (FF), or rats fed with formula supplemented with 1.5% of PSO (FF + PSO). All groups were exposed to asphyxia/cold stress to induce NEC. Intestinal injury, epithelial cell proliferation, cytokine production, and trefoil factor 3 (Tff3) production were evaluated in the terminal ileum. Oral administration of PSO (FF+PSO) decreased the incidence of NEC from 61 to 26%. Feeding formula with PSO improved enterocyte proliferation in the site of injury. Increased levels of proinflammatory IL-6, IL-8, IL-12, IL-23, and TNF-α in the ileum of FF rats were normalized in PSO-treated animals. Tff3 production in the FF rats was reduced compared with DF but not further affected by the PSO. In conclusion, administration of PSO protects against NEC in the neonatal rat model. This protective effect is associated with an improvement of intestinal epithelial homeostasis and a strong anti-inflammatory effect of PSO on the developing intestinal mucosa.
The currently available, standard soybean oil (SO)-based intravenous fat emulsions (IVFEs) meet the needs of most parenteral nutrition (PN) patients. There are alternative oil-based fat emulsions, such as medium-chain triglycerides (MCTs), olive oils (OOs), and fish oils (FOs), that, based on extensive usage in Europe, have an equivalent safety profile to SO. These alternative IVFEs are metabolized via different pathways, which may lead to less proinflammatory effects and less immune suppression. These alternative oil-based IVFEs are not currently available in the United States. Many patients who require IVFEs are already in a compromised state. Such patients could potentially have better clinical outcomes when receiving one of the alternative IVFEs to diminish the intake of the potentially proinflammatory ω-6 fatty acid-linoleic acid-which comprises more than 50% of the fatty acid profile in SO. Further research is needed on these alternative oil-based IVFEs to identify which IVFE oils or which combination of oils may be most clinically useful for specific patient populations.
Consumption of olive oil has been related to reduced risk of several diseases, including various neoplasms. In this paper, we reviewed epidemiological studies on olive oil and cancer published up to 2010. We performed a systematic literature search in the Medline database and, after assessment of relevant papers, we included 25 studies providing original data on olive oil consumption and cancer risk. We also performed a meta-analysis of studies of breast cancer, calculating the pooled relative risk (RR), and the corresponding 95% confidence intervals (CI), for high vs. low olive oil consumption. Several studies conducted in Southern Europe reported olive oil consumption as a favourable indicator of breast, digestive tract, and particularly upper aero-digestive tract cancers. For the latter, after adjustment for alcohol and tobacco use, the RRs between extreme levels of olive oil consumption were 0.3-0.4, and there was an over 5-fold difference in risk between subjects consuming mainly olive oil and those consuming mainly butter. The summary RR of breast cancer was 0.62 (95% CI, 0.44-0.88) for the highest vs. lowest level of olive oil consumption. Thus, preferring olive oil to other added lipids, particularly those rich in saturated fats, can decrease the risk of upper digestive and respiratory tract neoplasms, breast and, possibly, colorectal and other cancer sites.
Obesity is often associated with dyslipidemia, insulin resistance, and hypertension. Together, these metabolic perturbations greatly increase the risk of developing cardiovascular disease and diabetes. Although fish oil is a well-established hypolipidemic agent, the mechanisms by which it mediates its lipid-lowering effects are not clear. In addition, it has not been established whether dietary fish oil has different effects in lean and obese mice. LDL receptor deficient (LDLR-/-) and leptin deficient mice on a LDLR-/- background (ob/ob;LDLR-/-) were fed a high fat diet (39% total fat) supplemented with 6% olive oil or fish oil for 6 wk. Fish oil supplementation resulted in lower concentrations of plasma total cholesterol (P < 0.01), triglycerides (P < 0.01), and free fatty acids (P < 0.001) in lean LDLR-/- mice, but not in ob/ob;LDLR-/- mice. In contrast, a fish oil diet did not modulate insulin sensitivity in lean LDLR-/- mice, but it improved insulin sensitivity in ob/ob;LDLR-/- mice (P < 0.05) compared with olive oil fed ob/ob;LDLR-/- mice. Interestingly, plasma adiponectin concentrations were significantly higher and hepatic steatosis was reduced in both mouse models upon fish oil feeding. Finally, fish oil fed LDLR-/- mice exhibited higher hepatic AMP activated protein kinase (AMPK) phosphorylation (P < 0.05), whereas AMPK phosphorylation was not elevated by fish oil feeding in ob/ob;LDLR-/- mice. Taken together, our data suggest that fish oil reduces hepatic steatosis in both lean and obese mice, has potent plasma lipid lowering effects in lean mice, and exerts insulin sensitizing effects in obese mice.
Transient receptor potential (TRP) ion channels have been implicated in detecting chemical, thermal, and mechanical stimuli in organisms ranging from mammals to Caenorhabditis elegans. It is well established that TRPA1 detects and mediates behavioral responses to chemical irritants. However, the role of TRPA1 in detecting thermal and mechanical stimuli is controversial. To further clarify the functions of TRPA1 channels in vertebrates, we analyzed their roles in zebrafish. The two zebrafish TRPA1 paralogs are expressed in sensory neurons and are activated by several chemical irritants in vitro. High-throughput behavioral analyses of trpa1a and trpa1b mutant larvae indicate that TRPA1b is necessary for behavioral responses to these chemical irritants. However, TRPA1 paralogs are not required for behavioral responses to temperature changes or for mechanosensory hair cell function in the inner ear or lateral line. These results support a role for zebrafish TRPA1 in chemical but not thermal or mechanical sensing, and establish a high-throughput system to identify genes and small molecules that modulate chemosensation, thermosensation, and mechanosensation.
OBJECTIVE - To examine the socio-economic and lifestyle determinants of cooking oil choice in Costa Rica during the last decade (1994-2004).
DESIGN - Cross-sectional study. Subjects (total n = 2274) belonged to the control population of a large case-control study; they were recruited yearly. Data about type of oil used for cooking, dietary intake, socio-economic and demographic characteristics were collected.
SETTING - A dietitian visited all subjects and conducted the interviews at their homes; all subjects lived in the Costa Rican central valley region.
SUBJECTS - Adult, free-living, rural and urban Costa Ricans with no history of myocardial infarction and physical or mental disability.
RESULTS - The odds of choosing soybean over palm oil increased significantly each year (P < 0.05) and was determined by high socio-economic status (SES) and variables that suggest health awareness (self-reported history of hypertension, high cholesterol, multivitamin use and intake of green leafy vegetables). The odds of choosing other unsaturated oils, namely corn and sunflower, over soybean oil also increased yearly (P < 0.05) and was associated with the same two factors (high SES and health awareness). Palm oil users remained in the lowest SES tertile and were more likely to live in rural areas. Across all SES tertiles, high health awareness determined the odds of choosing other unsaturated oils over palm oil, and soybean oil (P < 0.05).
CONCLUSION - These data show that, in addition to SES, health awareness is associated with the selection of unsaturated oils over palm oil in a developing country undergoing transition. These data should be considered when targeting nutrition messages and policies that promote better dietary choices.
Palm oil and soybean oil are the 2 most widely used cooking oils in the world. Palm oil is consumed mainly in developing countries, where morbidity and mortality due to cardiovascular disease (CVD) are on the rise. Although claims about adverse or protective effects of these oils are commonly made, there are no epidemiologic studies assessing the association between these oils and cardiovascular disease endpoints. We examined whether consumption of palm oil relative to soybean oil and other unsaturated oils (predominantly sunflower) is associated with myocardial infarction (MI) in Costa Rica. The cases (n = 2111) were survivors of a first acute MI and were matched to randomly selected population controls (n = 2111). Dietary intake was assessed with a validated semiquantitative FFQ. Adipose tissue profiles of essential fatty acids were assessed to validate cooking oil intake and found to be consistent with self-reported major oils used for cooking. The data were analyzed using conditional logistic regression. Palm oil users were more likely to have an MI than users of soybean oil [odds ratio (OR) = 1.33; 95% CI: 1.08-1.63] or other cooking oils (OR = 1.23; CI: 0.99-1.52), but they did not differ from users of soybean oil with a high trans-fatty acid content (OR = 1.14; CI: 0.84-1.56). These data suggest that as currently used in Costa Rica, and most likely in many other developing countries, the replacement of palm oil with a polyunsaturated nonhydrogenated vegetable oil would reduce the risk of MI.