Melissa Hansen-Petrik

n3 and n6 polyunsaturated fatty acids differentially modulate prostaglandin E secretion but not markers of lipogenesis in adipocytes

A dramatic rise in the incidence of obesity in the U.S. has accelerated the search for interventions that may impact this epidemic. One recently recognized target for such intervention is adipose tissue, which secretes a variety of bioactive substances including prostaglandins. Prostaglandin E2 (PGE2) has been shown to decrease lipolysis in adipocytes, but limited studies have explored alternative mechanisms by which PGE2 might impact obesity, such as adipogenesis or lipogenesis. Studies conducted on ApcMin/+ mice indicated that selective inhibition of the cyclooxygenase (COX)-2 enzyme led to significant reductions in fatty acid synthase (FAS) activity in adipose tissue suggesting lipogenic effects of PGE2. To further investigate whether these lipid mediators directly regulate lipogenesis, we used 3T3-L1 adipocytes to determine the impact of eicosapentaenoic acid (EPA) and celecoxib on PGE2 formation and FAS used as a lipogenic marker. Both arachidonic acid (AA) and EPA dose-dependently increased PGE secretion from adipocytes. AA was expectedly more potent and exhibiting at 150 uM dose a 5-fold increase in PGE2 secretion over EPA. Despite higher secretion of PGE by EPA and AA compared to control, neither PUFA significantly altered FAS activity. By contrast both AA and EPA significantly decreased FAS mRNA levels. Addition of celecoxib, a selective COX-2 inhibitor, significantly decreased PGE2 secretion (p < 0.05) versus control, and also significantly decreased FAS activity (p < 0.05). Unexpectedly, the combination of exogenous PGE2 and celecoxib further decreased the FAS activity compared to PGE2 alone or untreated controls. In conclusion, EPA-mediated inhibition of AA metabolism did not significantly alter FAS activity while both AA and EPA significantly decreased FAS mRNA expression. COX-2 inhibition significantly decreased PGE2 production resulting in a decrease in FAS activity and expression that was not reversed with the addition of exogenous PGE2, suggesting an additional mechanism that is independent of COX-2.

Selective inhibition of Δ-6 desaturase impedes intestinal tumorigenesis

Arachidonic acid is an important polyunsaturated fatty acid involved in cell signaling. It is derived primarily from dietary linoleic acid, and the rate-limiting step in its biosynthesis is the initial desaturation of linoleic acid via Δ-6 desaturase. Evidence suggests that downstream metabolic products of arachidonic acid, e.g. prostaglandins, are involved in colorectal cancer, but involvement of the biosynthetic pathway of arachidonic acid has not been previously investigated. In the present study, we report the effects of a novel selective Δ-6 desaturase inhibitor, SC-26196, on tumorigenesis in two in vivo models of intestinal cancer. SC-26196 treatment resulted in 36–37% fewer tumors in ApcMin/+ mice and 35% decrease in primary tumor size in nude mice bearing HT-29 human colon cancer cell xenografts (P<0.05). As expected, SC-26196 treatment resulted in significantly higher linoleic acid levels in tissue phospholipids and lower levels of arachidonic acid. The effects on both tissue fatty acid composition and tumorigenesis in ApcMin/+ mice were abrogated by concomitant treatment with dietary arachidonic acid, indicating that the observed effects were due to interference with the biosynthetic pathway of arachidonic acid.

Use of Videoconferencing for Lactation Consultation: An Online Cross-Sectional Survey of Mothers’ Acceptance in the United States

Background: Suboptimal breastfeeding duration and exclusivity rates are a public health concern. Therefore, there is a need for identifying effective tools for use in interventions targeting specific barriers to optimal breastfeeding outcomes. Research aim: This study aimed to assess the relationship between acceptance of remote lactation consultation using videoconferencing and (a) maternal demographic factors, (b) technology acceptance subscales, (c) maternal learning style preferences, and (d) other potentially explanatory maternal factors. Methods: This was a cross-sectional, online study. English-speaking mothers of at least 18 years of age, with an infant age 4 months or younger, and who reported initiating breastfeeding were eligible to participate. Mothers were recruited from 27 randomly selected states. One hundred one mothers completed the survey, resulting in a response rate of 71%. The main outcome was acceptance of videoconferencing use for lactation consultation. Results: No significant differences were found in acceptance by maternal demographic factors or learning style preferences. Acceptance was significantly related to perceived ease of use (r = .680, p < .001), perceived usefulness/extrinsic motivation (r = .774, p < .001), intrinsic motivation (r = .689, p < .001), desire for control of privacy (r = –.293, p < .01), and mother’s perception of the infant father’s/maternal partner’s acceptance of videoconferencing for lactation consultation (r = .432, p < .001). Only perceived usefulness/extrinsic motivation and maternal age remained in the final regression model (R2 = .616, p < .001). Although perceived usefulness/extrinsic motivation was positively associated with acceptance, maternal age was inversely related. Conclusion: This sample of mothers indicated general acceptance of videoconferencing for lactation consultation, with younger mothers and those perceiving it to be more useful demonstrating greater acceptance.