Broader and safer clinically-relevant activities of pentadecanoic acid compared to omega-3: Evaluation of an emerging essential fatty acid across twelve primary human cell-based disease systems.

A growing body of evidence supports that pentadecanoic acid (C15:0), an odd-chain saturated fat found in butter, is an essential fatty acid that is necessary in the diet to support long-term metabolic and heart health. Here, dose dependent and clinically relevant cell-based activities of pure C15:0 (FA15TM) were compared to eicosapentaenoic acid (EPA), a leading omega-3 fatty acid, as well as to an additional 4,500 compounds. These studies included 148 clinically relevant biomarkers measured across 12 primary human cell systems, mimicking various disease states, that were treated with C15:0 at four different concentrations (1.9 to 50 μM) and compared to non-treated control systems. C15:0 was non-cytotoxic at all concentrations and had dose dependent, broad anti-inflammatory and antiproliferative activities involving 36 biomarkers across 10 systems. In contrast, EPA was cytotoxic to four cell systems at 50 μM. While 12 clinically relevant activities were shared between C15:0 and EPA at 17 μM, C15:0 had an additional 28 clinically relevant activities, especially anti-inflammatory, that were not present in EPA. Further, at 1.9 and 5.6 μM, C15:0 had cell-based properties similar to bupropion (Pearson's scores of 0.78), a compound commonly used to treat depression and other mood disorders. At 5.6 μM, C15:0 mimicked two antimicrobials, climabazole and clarithromycin (Pearson's scores of 0.76 and 0.75, respectively), and at 50 μM, C15:0 activities matched that of two common anti-cancer therapeutics, gemcitabine and paclitaxel (Pearson's scores of 0.77 and 0.74, respectively). In summary, C15:0 had dose-dependent and clinically relevant activities across numerous human cell-based systems that were broader and safer than EPA, and C15:0 activities paralleled common therapeutics for mood disorders, microbial infections, and cancer. These studies further support the emerging role of C15:0 as an essential fatty acid

Data from: Increased dietary intake of saturated fatty acid heptadecanoic acid (C17:0) associated with decreasing ferritin and alleviated metabolic syndrome in dolphins

Similar to humans, bottlenose dolphins (Tursiops truncatus) can develop metabolic syndrome and associated high ferritin. While fish and fish-based fatty acids may protect against metabolic syndrome in humans, findings have been inconsistent. To assess potential protective factors against metabolic syndrome related to fish diets, fatty acids were compared between two dolphin populations with higher (n = 30, Group A) and lower (n = 19, Group B) mean insulin (11 ± 12 and 2 ± 5 μIU/ml, respectively; P < 0.0001) and their dietary fish. In addition to higher insulin, triglycerides, and ferritin, Group A had lower percent serum heptadecanoic acid (C17:0) compared to Group B (0.3 ± 0.1 and 1.3 ± 0.4%, respectively; P < 0.0001). Using multivariate stepwise regression, higher percent serum C17:0, a saturated fat found in dairy fat, rye, and some fish, was an independent predictor of lower insulin in dolphins. Capelin, a common dietary fish for Group A, had no detectable C17:0, while pinfish and mullet, common in Group B’s diet, had C17:0 (41 and 67 mg/100g, respectively). When a modified diet adding 25% pinfish and/or mullet was fed to six Group A dolphins over 24 weeks (increasing the average daily dietary C17:0 intake from 400 to 1700 mg), C17:0 serum levels increased, high ferritin decreased, and blood-based metabolic syndrome indices normalized toward reference levels. These effects were not found in four reference dolphins. Further, higher total serum C17:0 was an independent and linear predictor of lower ferritin in dolphins in Group B dolphins. Among off the shelf dairy products tested, butter had the highest C17:0 (423mg/100g); nonfat dairy products had no detectable C17:0. We hypothesize that humans’ movement away from diets with potentially beneficial saturated fatty acid C17:0, including whole fat dairy products, could be a contributor to widespread low C17:0 levels, higher ferritin, and metabolic syndrome

Development and testing of species-specific ELISA assays to measure IFN-γ and TNF-α in bottlenose dolphins (<i>Tursiops truncatus</i>)

<div><p>Monitoring the immune status of cetaceans is important for a variety of health conditions. Assays to quantify cytokines, especially pro-inflammatory cytokines, could be employed, in addition to currently available diagnostic assays, to screen for alterations in the health status of an animal. Though a number of immunological assays are readily available for humans and mice, specific assays for many veterinary species, including cetaceans such as bottlenose dolphins (<i>Tursiops truncatus)</i>, are more limited. Herein, we describe the development of IFN-gamma (IFN-γ) and TNF-alpha (TNF-α) enzyme-linked immunosorbent assays (ELISAs) specific to bottlenose dolphins. Utilizing these assays, we monitored the immune status of bottlenose dolphins from a managed population over a period of eleven months. The ELISA assays developed for bottlenose dolphins were used to measure IFN-γ and TNF-α in serum or in culture supernatants from peripheral blood mononuclear cells (PBMCs) stimulated with varying concentrations of mitogens concanavalin A (ConA) or phytohemagglutinin (PHA). Induction of TNF-α in PBMC cultures was consistently highest with 1 μg/mL ConA, while 1 μg/mL PHA induced the highest secretion of IFN-γ. Serum levels of TNF-α and IFN-γ remained relatively constant for each animal over the time period examined. CBC and plasma chemistry variables measured concurrently in the bottlenose dolphins were then examined as independent predictors of cytokine levels. We found these clinical variables were more likely to predict linear changes in serum IFN-γ and TNF-α levels compared to concentrations of these cytokines in mitogen-stimulated PBMC culture supernatants. Cytokine assays developed will be of substantial benefit in monitoring bottlenose dolphin health as an adjunct to currently available diagnostic tests.</p></div

Bottlenose dolphin (<i>Tursiops truncatus</i>) clinical information.

<p>Bottlenose dolphin (<i>Tursiops truncatus</i>) clinical information.</p

Time course of IFN-γ (ng/mL) levels in supernatants from ConA or PHA stimulated PBMCs isolated from bottlenose dophins (<i>Tursiops truncatus</i>).

<p>PBMCs isolated from <i>Tursiops truncatus</i> were stimulated with 1, 5, or 10 μg/mL PHA or 1 μg/mL ConA for 48 hours in culture. Supernatants were collected and run on an ELISA assay specific for bottlenose dolphin IFN-γ as described in Materials and Methods. Samples were collected monthly over an 11-month period from four bottlenose dolphins (Animals A, B, C, and D). Month of the study is denoted on the x-axis and month 1 corresponds to June 2014.</p

Summary of blood-based health indices that independently predicted a linear change in IFN-γ and TNF-α levels in bottlenose dolphins (<i>Tursiops truncatus</i>).

<p>Summary of blood-based health indices that independently predicted a linear change in IFN-γ and TNF-α levels in bottlenose dolphins (<i>Tursiops truncatus</i>).</p