Human fetal intestinal epithelial cells metabolize and incorporate branched chain fatty acids in a structure specific manner.

Background: Branched chain fatty acids (BCFA) are constituents of gastrointestinal (GI) tract in healthy newborn human infants, reduce the incidence of necrotizing enterocolitis (NEC) in a neonatal rat model, and are incorporated into small intestine cellular lipids in vivo. We hypothesize that BCFA are taken up, metabolized and incorporated into human fetal cells in vitro.

Methods: Human H4 cells, a fetal non-transformed primary small intestine cell line, were incubated with albumin-bound non-esterified anteiso-17:0, iso-16:0, iso-18:0 and/or iso-20:0, and FA profiles in lipid fractions were analyzed.

BCFA suppresses LPS induced IL-8 mRNA expression in human intestinal epithelial cells.

Branched chain fatty acids (BCFA) are components of common food fats and are major constituents of the normal term human newborn GI tract. Polyunsaturated fatty acids (PUFA) have been suggested to reduce the risk and development of inflammatory bowel diseases (IBD); however, little is known about the influence of BCFA on inflammation. We investigated the effect of BCFA on interleukin (IL)-8 and NF-κB production in a human intestinal epithelial cell line (Caco-2).

Metabolic fate of docosahexaenoic acid (DHA; 22:6n-3) in human cells: direct retroconversion of DHA to eicosapentaenoic acid (20:5n-3) dominates over elongation to tetracosahexaenoic acid (24:6n-3).

Docosahexaenoic acid (22:6n-3) supplementation in humans causes eicosapentaenoic acid (20:5n-3) levels to rise in plasma, but not in neural tissue where 22:6n-3 is the major omega-3 in phospholipids. We determined whether neuronal cells (Y79 and SK-N-SH) metabolize 22:6n-3 differently from non-neuronal cells (MCF7 and HepG2). We observed that (13) C-labeled 22:6n-3 was primarily esterified into cell lipids.

Regular-Fat Dairy and Human Health: A Synopsis of Symposia Presented in Europe and North America (2014-2015).

In recent history, some dietary recommendations have treated dairy fat as an unnecessary source of calories and saturated fat in the human diet. These assumptions, however, have recently been brought into question by current research on regular fat dairy products and human health. In an effort to disseminate, explore and discuss the state of the science on the relationship between regular fat dairy products and health, symposia were programmed by dairy industry organizations in Europe and North America at The Eurofed Lipids Congress (2014) in France, The Dairy Nutrition Annual Symposium (2014) in Canada, The American Society for Nutrition Annual Meeting held in conjunction with Experimental Biology (2015) in the United States, and The Federation of European Nutrition Societies (2015) in Germany.

Arachidonic acid needed in infant formula when docosahexaenoic acid is present.

Recently, the European Food Safety Authority asserted that arachidonic acid (ARA) is an optional nutrient for the term infant even when docosahexaenoic acid (DHA) is present. The brief rationale is based on an explicit, widespread misapplication of the concept of "essential fatty acids" to linoleic acid that implies it is uniquely required as a nutrient per se. Linoleic acid prevents acute clinical symptoms caused by polyunsaturated fatty acid-deficient diets and is the major precursor for ARA in most human diets.

Long-chain polyunsaturated fatty acids and the preterm infant: a case study in developmentally sensitive nutrient needs in the United States.

The vast majority of infant formulas in the United States contain the long-chain polyunsaturated fatty acids (PUFAs) docosahexaenoic acid (22:6n-3) and arachidonic acid (20:4n-6), which were first permitted by the US Food and Drug Administration in 2001. As a scientific case study, preclinical animal studies of these nutrients definitively influenced the design and interpretation of human clinical studies. Early studies were tied to the availability of test substances, and in hindsight suggest re-evaluation of the essential fatty acid concept in light of the totality of available evidence.

Palmitic acid (16:0) competes with omega-6 linoleic and omega-3 ɑ-linolenic acids for FADS2 mediated Δ6-desaturation.

Sapienic acid, 16:1n-10 is the most abundant unsaturated fatty acid on human skin where its synthesis is mediated by FADS2 in the sebaceous glands. The FADS2 product introduces a double bond at the Δ6, Δ4 and Δ8 positions by acting on at least ten substrates, including 16:0, 18:2n-6, and 18:3n-3. Our aim was to characterize the competition for accessing FADS2 mediated Δ6 desaturation between 16:0 and the most abundant polyunsaturated fatty acids (PUFA) in the human diet, 18:2n-6 and 18:3n-3, to evaluate whether competition may be relevant in other tissues and thus linked to metabolic abnormalities associated with FADS2 or fatty acid levels.

The European Food Safety Authority recommendation for polyunsaturated fatty acid composition of infant formula overrules breast milk, puts infants at risk, and should be revised.

The European Food Safety Authority (EFSA) has concluded from a limited review of the literature that although docosahexaenoic acid (DHA) is required for infant formula, arachidonic acid is not required "even in the presence of DHA" (EFSA Journal, 12 (2014) 3760). This flawed opinion is grounded in human trials which tested functionality of DHA in neural outcomes and included arachidonic acid ostensibly to support growth. The EFSA report mistakes a nutrient ubiquitous in the diets of newborn infants, through breast milk and with wide-ranging health and neurodevelopmental effects, for an optional drug targeted to a particular outcome that is properly excluded when no benefit is found for that particular outcome.

The fatty acid desaturase 2 (FADS2) gene product catalyzes Δ4 desaturation to yield n-3 docosahexaenoic acid and n-6 docosapentaenoic acid in human cells.

Docosahexaenoic acid (DHA) is a Δ4-desaturated C22 fatty acid and the limiting highly unsaturated fatty acid (HUFA) in neural tissue. The biosynthesis of Δ4-desaturated docosanoid fatty acids 22:6n-3 and 22:5n-6 are believed to proceed via a circuitous biochemical pathway requiring repeated use of a fatty acid desaturase 2 (FADS2) protein to perform Δ6 desaturation on C24 fatty acids in the endoplasmic reticulum followed by 1 round of β-oxidation in the peroxisomes. We demonstrate here that the FADS2 gene product can directly Δ4-desaturate 22:5n-3→22:6n-3 (DHA) and 22:4n-6→22:5n-6.

Balancing omega-6 and omega-3 fatty acids in ready-to-use therapeutic foods (RUTF).

Ready-to-use therapeutic foods (RUTFs) are a key component of a life-saving treatment for young children who present with uncomplicated severe acute malnutrition in resource limited settings. Increasing recognition of the role of balanced dietary omega-6 and omega-3 polyunsaturated fatty acids (PUFA) in neurocognitive and immune development led two independent groups to evaluate RUTFs. Jones et al.

Quantitative analysis of volatiles in edible oils following accelerated oxidation using broad spectrum isotope standards.

Analysis of food volatiles generated by processing are widely reported but comparisons across studies is challenging in part because most reports are inherently semi-quantitative for most analytes due to limited availability of chemical standards. We recently introduced a novel strategy for creation of broad spectrum isotopic standards for accurate quantitative food chemical analysis. Here we apply the principle to quantification of 25 volatiles in seven thermally oxidised edible oils.

Docosahexaenoic acid and human brain development: evidence that a dietary supply is needed for optimal development.

Humans evolved a uniquely large brain among terrestrial mammals. Brain and nervous tissue is rich in the omega-3 polyunsaturated fatty acid (PUFA) docosahexaenoic acid (DHA). Docosahexaenoic acid is required for lower and high order functions in humans because of understood and emerging molecular mechanisms.

Dietary zinc deficiency affects blood linoleic acid: dihomo-γ-linolenic acid (LA:DGLA) ratio; a sensitive physiological marker of zinc status in vivo (Gallus gallus).

Zinc is a vital micronutrient used for over 300 enzymatic reactions and multiple biochemical and structural processes in the body. To date, sensitive and specific biological markers of zinc status are still needed. The aim of this study was to evaluate Gallus gallus as an in vivo model in the context of assessing the sensitivity of a previously unexplored potential zinc biomarker, the erythrocyte linoleic acid: dihomo-γ-linolenic acid (LA:DGLA) ratio.

Fatty acid analysis by high resolution gas chromatography and mass spectrometry for clinical and experimental applications.

Purpose Of Review: Quantitative fatty acid profiles analyzed via fatty acid methyl esters (FAME) are among the most common metabolite panels and fit into the category of omics techniques. Recently, preparation and analysis methods for high throughput clinical analysis have become routine, and novel methods for structure analysis enable rapid identification of unknowns and confounded peaks.

Recent Findings: Observation of one hundred FAME in a single mixture is common with high resolution capillary gas chromatography columns.

Plasma oxylipin profiling identifies polyunsaturated vicinal diols as responsive to arachidonic acid and docosahexaenoic acid intake in growing piglets.

The dose-responsiveness of plasma oxylipins to incremental dietary intake of arachidonic acid (20:4n-6; ARA) and docosahexaenoic acid (22:6n-3; DHA) was determined in piglets. Piglets randomly received one of six formulas (n = 8 per group) from days 3 to 27 postnatally. Diets contained incremental ARA or incremental DHA levels as follows (% fatty acid, ARA/DHA): (A1) 0.

The polypyrimidine tract binding protein regulates desaturase alternative splicing and PUFA composition.

The Δ6 desaturase, encoded by FADS2, plays a crucial role in omega-3 and omega-6 fatty acid synthesis. These fatty acids are essential components of the central nervous system, and they act as precursors for eicosanoid signaling molecules and as direct modulators of gene expression. The polypyrimidine tract binding protein (PTB or hnRNP I) is a splicing factor that regulates alternative pre-mRNA splicing.

Animal studies of the functional consequences of suboptimal polyunsaturated fatty acid status during pregnancy, lactation and early post-natal life.

Scores of animal studies demonstrate that seed oils replete with linoleic acid and very low in linolenic acid fed as the exclusive source of fat through pregnancy and lactation result in visual, cognitive, and behavioural deficits in the offspring. Commodity peanut, sunflower, and safflower oils fed to mother rats, guinea pigs, rhesus monkeys, and baboons induce predictable changes in tissue polyunsaturated fatty acid composition that are abnormal in free-living land mammals as well as changes in neurotransmitter levels, catecholamines, and signalling compounds compared with animals with a supply of ω3 polyunsaturated fatty acid. These diets consistently induce functional deficits in electroretinograms, reflex responses, reward or avoidance induced learning, maze learning, behaviour, and motor development compared with ω3 replete groups.

Alternative transcripts of fatty acid desaturase (FADS) genes.

Alternative splicing is a major mechanism for increasing the range of products encoded by the genome. We recently reported positive identification of the first alternative transcripts (AT) of fatty acid desaturase 3 (FADS3) and FADS2 in fetal and neonatal baboons. FADS3, a putative polyunsaturated fatty acid (PUFA) desaturase gene with no known function, has 7 AT that are expressed in at least twelve organs in an apparently constitutive manner.

alpha-Linolenic acid supplementation and conversion to n-3 long-chain polyunsaturated fatty acids in humans.

Blood levels of polyunsaturated fatty acids (PUFA) are considered biomarkers of status. Alpha-linolenic acid, ALA, the plant omega-3, is the dietary precursor for the long-chain omega-3 PUFA eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA). Studies in normal healthy adults consuming western diets, which are rich in linoleic acid (LA), show that supplemental ALA raises EPA and DPA status in the blood and in breast milk.

The influence of dietary docosahexaenoic acid and arachidonic acid on central nervous system polyunsaturated fatty acid composition.

Numerous studies on perinatal long-chain polyunsaturated fatty acid nutrition have clarified the influence of dietary docosahexaenoic acid (DHA) and arachidonic acid (ARA) on central nervous system PUFA concentrations. In humans, omnivorous primates, and piglets, DHA and ARA plasma and red blood cells concentrations rise with dietary preformed DHA and ARA. Brain and retina DHA are responsive to diet while ARA is not.