Tom Brenna

Tom Brenna
Cornell University | CU

About

382
Publications
43,337
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12,893
Citations
Citations since 2017
87 Research Items
5258 Citations
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201720182019202020212022202302004006008001,000
201720182019202020212022202302004006008001,000
201720182019202020212022202302004006008001,000
Introduction
Skills and Expertise

Publications

Publications (382)
Article
Full-text available
Ready-to-use therapeutic food (RUTF) is used to treat young children diagnosed with severe acute malnutrition. RUTF with low and balanced linoleic and alpha-linolenic acid, plus omega-3 docosahexaenoic acid (DHA), supports long-term cognitive recovery. DHA is prone to degradation due to peroxidation, possibly exacerbated by the iron inherently in R...
Article
Ru-based catalysis results in highly unsaturated fatty acid (HUFA) ethyl esters (EE) deuterated to various extents. The products carry 2H (D) mainly at their bis-allylic positions, where they are resistant to autoxidation compared to natural HUFA and are promising as neurological and retinal drugs. We characterized the extent of deuteration at each...
Article
Docosahexaenoic acid (DHA; 22:6n-3) rich photoreceptors function in a highly oxidizing microenvironment. Lipid peroxidation and inflammation contribute to initiation and progression of eye diseases including age-related macular degeneration (AMD). Deuteration of DHA at the bis-allylic positions (D-DHA) increases its resilience to oxidative damage i...
Article
Full-text available
Beige adipocytes are induced by cold temperatures or β3-adrenergic receptor (Adrb3) agonists. They create heat through glucose and fatty acid (FA) oxidation, conferring metabolic benefits. The distinct and shared mechanisms by which these treatments induce beiging are unknown. Here, we perform single-nucleus assay for transposase-accessible chromat...
Article
Full-text available
Background Dietary methyl donors (e.g., choline) support the activity of the phosphatidylethanolamine N-methyltransferase (PEMT) pathway, which generates phosphatidylcholine (PC) molecules enriched in docosahexaenoic acid (DHA) that are exported from the liver and made available to extrahepatic tissues. Objective This study investigated the effect...
Article
Full-text available
Polyunsaturated fatty acids (PUFAs) are structural components of membrane phospholipids, and influence cellular function via effects on membrane properties, and also by acting as a precursor pool for lipid mediators. These lipid mediators are formed via activation of pathways involving at least one step of dioxygen-dependent oxidation, and are cons...
Preprint
Full-text available
Beige adipocytes are induced by cold temperatures or β3-adrenergic receptor (Adrb3) agonists. They create heat through glucose and fatty acid (FA) oxidation, conferring metabolic benefits. The distinct and shared mechanisms by which these treatments induce beiging are unknown. Here, we performed single-nucleus assay for transposase-accessible chrom...
Article
Circulating fatty acids (FA) may be important in the psoriatic pro-inflammatory phenotype. FADS1 converts linoleic acid (LA) to arachidonic acid (AA), a precursor to potent signaling molecules. HMG-CoA reductase inhibitors (statins) increase FADS1/2 expression in vitro. Psoriasis patients (42 ± 14 years/age, 47% male) were randomized to 40mg of ato...
Article
Full-text available
Arachidonic acid (ARA) is a major component of lipid bilayers as well as the key substrate for the eicosanoid cascades. ARA is readily oxidized, and its non-enzymatic and enzymatic oxidation products induce inflammatory responses in nearly all tissues, including lung tissues. Deuteration at bis-allylic positions substantially decreases the overall...
Article
Full-text available
Oxidative stress plays a central role in age-related macular degeneration (AMD). Iron, a potent generator of hydroxyl radicals through the Fenton reaction, has been implicated in AMD. One easily oxidized molecule is docosahexaenoic acid (DHA), the most abundant polyunsaturated fatty acid in photoreceptor membranes. Oxidation of DHA produces toxic o...
Article
Many current treatment options for lung inflammation and thrombosis come with unwanted side effects. The natural omega-3 fatty acids (O3FA) are generally anti-inflammatory and antithrombotic. O3FA are always administered orally and occasionally by intravenous (IV) infusion. The main goal of this study is to determine if O3FA administered by inhalat...
Article
Full-text available
Obesity promotes type 2 diabetes and cardiometabolic pathologies. Vertical sleeve gastrectomy (VSG) is used to treat obesity resulting in long-term weight loss and health improvements that precede weight loss; however, the mechanisms underlying the immediate benefits remain incompletely understood. Because adipose plays a crucial role in energy hom...
Article
Purpose of review: Molecular studies have clarified the roles of the fatty acid desaturase (FADSx) and elongation of very long chain fatty acid (ELOVLx) genes, as well as acyl-coenzyme A synthase long-chain isoforms (ACSLx) required for entry to long-chain polyunsaturated fatty acid (LCPUFA) biosynthetic pathways. Recent findings: FADS1 and FADS...
Article
Full-text available
Background: There is concern that the polyunsaturated fatty acid (PUFA) composition of ready-to-use therapeutic food (RUTF) for treatment of severe acute malnutrition (SAM) is suboptimal for neurocognitive recovery. Objective: We tested the hypothesis that RUTF made with reduced amounts of linoleic acid, achieved using high oleic (HO) peanuts wi...
Article
Full-text available
The last decade has seen nearly 20 papers reviewing the totality of the data on saturated fats and cardiovascular outcomes, which, altogether, have demonstrated a lack of rigorous evidence to support continued recommendations either to limit the consumption of saturated fatty acids or to replace them with polyunsaturated fatty acids. These papers w...
Preprint
Full-text available
Background: There is concern that the PUFA composition of ready-to-use therapeutic food (RUTF) for treatment of severe acute malnutrition (SAM) is suboptimal for neurocognitive recovery. Objective: We tested the hypothesis that RUTF made with reduced amounts of linoleic acid, achieved using high oleic (HO) peanuts, with or without added DHA, improv...
Article
Sea urchin (class Echinoidea) gonads are a prized delicacy in Japan and many other world cultures. The complexity of its fatty acid (FA) profile, particularly minor FA, presents a formidable analytical challenge. We applied solvent mediated (SM) covalent adduct chemical ionization (CACI) tandem mass spectrometry to comprehensive de novo structural...
Preprint
Full-text available
Obesity promotes type 2 diabetes and cardiometabolic pathologies. Vertical sleeve gastrectomy (VSG) is used to treat obesity resulting in long-term weight loss and health improvements that precede weight loss; however, the mechanisms underlying the immediate benefits remain incompletely understood. Because adipose plays a crucial role in energy hom...
Article
Full-text available
The omega-3 fatty acid docosahexaenoic acid (DHA) inversely relates to neurological impairments with aging; however, limited nondietary models manipulating brain DHA have hindered a direct linkage. We discovered that loss of long-chain acyl-CoA synthetase 6 in mice (Acsl6–/–) depletes brain membrane phospholipid DHA levels, independent of diet. Her...
Article
Background The roles of omega-3 (n3) fatty acids [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] and low-dose aspirin in the primary prevention of ischemic cardiovascular disease (CVD) are controversial. Since omega-3 (n3) fatty acids and aspirin affect cyclooxygenase activity in platelets, there could be a clinically-relevant effect o...
Article
Purpose. Plasticity in fatty acid metabolism is increasingly recognized as a major feature influencing cancer progression and efficacy of treatments. Estrogen receptor positive MCF7 human breast cancer cells have long been known to have no FADS2-mediated Δ6-desaturase activity. Our objective was to examine the effect of estrogen and the “antiestrog...
Article
Studies in mice using germfree animals as controls for microbial colonization have shown that the gut microbiome mediates diet-induced obesity. Such studies use diets rich in saturated fat, however, Western diets in the USA are enriched in soybean oil, composed of unsaturated fatty acids (FAs), either linoleic or oleic acid. Here, we addressed whet...
Article
Aquatic-to-terrestrial subsidies have the potential to provide riparian consumers with benefits in terms of physiologically important organic compounds like omega-3 long-chain polyunsaturated fatty acids (n-3 LCPUFAs). However, they also have a "dark side" in the form of exposure to toxicants such as mercury. Human land use intensity may also deter...
Article
The FACS workshops owe their origin to a gift by the prolific fatty acid scientist, entrepreneur and founding editor of this journal, the late David Horrobin, intended to conduct a small invitation-only meeting on a themed topic on fatty acid science with active researchers. Since that first 1992 workshop in Paris, FACS has been held about every se...
Preprint
Background: The unusual phosphatidylcholine species, dilauroylphosphatidylcholine (DLPC), has been reported to bind and activate the orphan nuclear receptor, liver receptor homolog-1 (LRH-1). To date, DLPC has not been reported endogenously in metabolomic databases. Objective: Herein, we test the hypothesis that the provision of the acyl constituen...
Article
Dairy and fermented foods are common sources of dietary branched-chain fatty acids (BCFA) of chain lengths C13-C18 serving a putative prebiotic role and a component of human integument. Few studies have reported on nonfermented plant-derived BCFA in human diets or cosmetics. A three-ion monitoring method was adapted to confirm branch position of ul...
Article
COVID-19 symptoms vary from silence to rapid death, the latter mediated by both a cytokine storm and a thrombotic storm. SARS-CoV (2003) induces Cox-2, catalyzing the synthesis, from highly unsaturated fatty acids (HUFA), of eicosanoids and docosanoids that mediate both inflammation and thrombosis. HUFA balance between arachidonic acid (AA) and oth...
Preprint
Full-text available
Studies in mice using germfree animals as controls for microbial colonization have shown that the gut microbiome mediates diet-induced obesity. Such studies use diets rich in saturated fat, however, Western diets in the USA are enriched in soybean oil, composed of unsaturated fatty acids (FAs), either linoleic or oleic acid. Here we addressed wheth...
Article
Full-text available
RT001 is the di-deutero isotopologue of linoleic acid ethyl ester (D2-LA). Resistance to oxidative damage at the carbon-deuterium bond depends upon the concentration of D2-LA as a percentage of total LA. We report here on the plasma and red cell (RBC) pharmacokinetics (PK) of D2-LA, and its metabolite 13,13-D2-arachidonic acid (D2-AA), in patients...
Article
Rationale Quantitative analysis of triacylglycerols (TAG) is impeded by a lack of standards and the huge number of potential TAG molecular species that may be present due to the combinatorial nature of glycerolipids. Randomization of acyl groups yields TAG mixtures with profiles predictable from fatty acid profiles; however, their use as calibratio...
Article
The net action of ruminal bacteria and endogenous bovine enzymes are responsible for cow's milk having the most complex fatty acid profiles among common foods. About 40 monounsaturated fatty acids below 1.5% w/w are known. Analysis of trace and ultratrace fatty acids is a challenge to the highest resolution chromatography even with prior fractionat...
Article
Objectives Our main aim is to test the effect of estrogen and antiestrogen (letrozole) on the modulation of fatty acid desaturation and ScA levels in vitro using human cancer cells. Methods We used two sets of cells, MCF7 cells stably expressing FADS1 and FADS2 genes and a series of wild type (MCF7, HepG2, SK-N-SH, Caco2 and Y79) cancer cells. Cel...
Article
Objectives Branched chain fatty acids (BCFA), linear chain/normal odd chain fatty acids (n-OCFA) and sapienic acid (16:1n-10), are the most abundant lipids on human skin, especially sebaceous gland (SG) wax esters. Sapienic acid synthesis is mediated by fatty acid desaturase 2 (FADS2) in the sebaceous glands. FADS2 is an abundant mRNA in human skin...
Article
Full-text available
The recommendation to limit dietary saturated fatty acid (SFA) intake has persisted despite mounting evidence to the contrary. Most recent meta-analyses of randomized trials and observational studies found no beneficial effects of reducing SFA intake on cardiovascular disease (CVD) and total mortality, and instead found protective effects against s...
Article
Type 2 Diabetes mellitus is associated with aging and shortened telomere length. Telomerase replaces lost telomeric repeats at the ends of chromosomes and is necessary for the replicative immortality of cells. Aspirin and the n3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are commonly used therapies in people with type 2...
Article
Pine nuts and other edible gymnosperm seeds contain unusual, bioactive polymethylene-interrupted polyunsaturated fatty acids (PMI-PUFAs), a subset of nonmethylene-interrupted PUFA with (-CH2-)n≥2 intervening between double bonds. Conventional methods for structure elucidation of PMI-PUFAs require special derivatization risking rearrangement artifac...
Article
Fatty acid analysis of food lipids containing branched chain fatty acids (BCFAs) are complex because of unavoidable gas chromatography (GC) co-elution. We demonstrate a method for convenient quantitative GC coupled to novel solvent-mediated chemical ionization (CI) mass spectrometry (MS) that enables resolution of co-eluting peaks by mass. The rele...
Article
Full-text available
Dairy has been described as everything from a superfood to a poison; yet, arguments, assumptions, and data justifying these labels are not always clear. We used an issue-based information system, “dialogue mapping™,” to summarize scientific points of a live panel discussion on the putative effects of dairy on cardiovascular diseases (CVD) from a da...
Article
Full-text available
Sphingolipids (SL) are structurally diverse lipids that are defined by the presence of a long chain base (LCB) backbone. Typically, LCBs contain a single Δ4E DB (mostly d18:1), whereas the dienic LCB sphingadienine (d18:2) contains a second DB at Δ14Z position. The enzyme introducing the Δ14Z DB is unknown. We analyzed the LCB plasma profile in a g...
Article
Full-text available
Dried blood spots for fatty acid profiling are increasing in popularity; however, variability in results between laboratories has not been characterized. Whole blood from two subjects (low and high n‐3 polyunsaturated fatty acid [PUFA] status) was collected, 25 μL applied to butylated hydroxytoluene (BHT)‐treated chromatography strips, dried in air...
Article
Monounsaturated normal fatty acids (n-MUFA) and saturated branched chain fatty acids (BCFA) are structurally characterized by separate tandem mass spectrometry methods for double bond localization and for chain branching in their respective fatty acid methyl ester (FAME) derivatives, however these methods have never been applied to branched monouns...
Article
Branched chain fatty acids (BCFA) and linear chain/normal odd chain fatty acids (n-OCFA) are major fatty acids in human skin lipids, especially sebaceous gland (SG) wax esters. Skin lipids contain variable amounts of monounsaturated BCFA and n-OCFA, in some reports exceeding over 20% of total fatty acids. Fatty acid desaturase 2 (FADS2) codes for a...
Article
Conjugated linolenic acids (CLnAs) are natural phytochemicals with known and potential bioactivities in mammals. Established CLnA sources are limited to a few common fruit seeds, notably pomegranate seeds and cherry pits, and the search for alternatives is impeded in part by cumbersome methods for reliable measurement. We investigated CLnA contents...
Article
The major facilitator superfamily domain 2a protein was identified recently as a lysophosphatidylcholine (LPC) symporter with high affinity for LPC species enriched with DHA (LPC-DHA). To test the hypothesis that reproductive state and choline intake influence plasma LPC-DHA, we performed a post-hoc analysis of samples available through 10 weeks of...
Article
Reproductive state and choline intake influence enrichment of plasma lysophosphatidylcholine-DHA: a post-hoc analysis of a controlled feeding trial - Kevin C. Klatt, Melissa Q. McDougall, Olga V. Malysheva, J. Thomas Brenna, Mark S. Robertson, Marie A. Caudill
Article
Full-text available
Docosahexaenoic acid (DHA) is an omega(ω)-3 dietary-derived polyunsaturated fatty acid of marine origin enriched in testes and necessary for normal fertility, yet the mechanisms regulating the enrichment of DHA in the testes remain unclear. Long-chain acyl-CoA synthetase isoform 6 (ACSL6) activates fatty acids for cellular anabolic and catabolic me...
Article
1.Aquatic and terrestrial ecosystems are connected through reciprocal fluxes of energy and nutrients that can subsidize consumers. Past research on reciprocal aquatic‐terrestrial subsidies to consumers has generally focused on subsidy quantity while ignoring major differences in the nutritional composition of aquatic and terrestrial resources. Beca...
Article
Objectives Saturated branched chain fatty acids (BCFA) terminating with either an isopropyl or sec-butyl group, are common bioactive food components consumed from beef, fish, and dairy products. Little is known about their endogenous metabolism and the enzymes mediating their interconversion. Our main objective was to test the substrate specificity...
Article
Objectives The product of linoleic acid elongation, 20:2n-6, is the only known substrate for both FADS1 and FADS2. FADS1 catalyzes 20:2n-6 à 5Z,11Z,14Z-20:3 (sciadonic acid, SA), whereas FADS2 action yields 8Z,11Z,14Z-20:3 (DGLA). In certain cancer cell types, non-functional FADS2 activity unmasks 18:2n-6 elongation to 20:2n-6 and Δ5 desaturation b...
Article
Saturated branched chain fatty acids (BCFA) terminating with either an isopropyl or sec‐butyl group are common bioactive food components consumed from beef, fish, and dairy products. Little is known about the endogenous metabolism of BCFA and the enzymes mediating their interconversions. By using transient transfection studies, we report for the fi...
Article
Despite its 50-year history, the conventional diet-heart hypothesis holding that dietary saturated fats raise serum cholesterol, and with it, cardiovascular risk, remains controversial. Harsh chemical and physical treatment generates process contaminants, and refined oils raise serum and tissue cholesterol in vivo independent of saturated fat conte...
Article
Metal oxide-filled reactors constructed with ceramic tubes or fused silica capillary are widely used for combustion in gas chromatography combustion isotope ratio mass spectrometry (GCC-IRMS). However, they tend to be easily cracked or broken and prone to leaks at operating temperatures of ∼950 °C. Here we introduce a modified commercially availabl...
Article
Full-text available
The aim of this study was to determine if the dietary pattern of pregnant women has any compensatory effect on the fatty acid desaturase (FADS) gene expression, thus enhancing the conversion of precursors to long chain polyunsaturated fatty acids (LCPUFA) to spare the overall LCPUFA levels. The dietary intake of plant-based precursor polyunsaturate...
Article
D‐PUFAs have recently emerged as a non‐antioxidant approach to resisting lipid peroxidation, the major player in aging and age‐related disease. We report results on dietary D‐PUFAs in mice and rats in vivo indicating good tolerability in both species. In rats overexpressing human A53T α‐synuclein in substantia nigra, D‐PUFA diet improved sensorimot...
Article
The mean intake (500 mg/day) of branched chain fatty acids (BCFA) in western countries is from dairy products and beef. We hypothesized that Asian countries with low dairy consumption have an alternative source of BCFA and report the characterization of nātto and selected fermented foods for BCFA content. Nātto BCFA averaged 0.6 (range 0.21–1.43) m...
Article
Normal odd-chain SFA (OCSFA), particularly tridecanoic acid ( n -13 : 0), pentadecanoic acid ( n -15 : 0) and heptadecanoic acid ( n -17 : 0), are normal components of dairy products, beef and seafood. The ratio of n -15 : 0: n -17 : 0 in ruminant foods (dairy products and beef) is 2:1, while in seafood and human tissues it is 1:2, and their appear...
Article
The role of lipid metabolism in epithelial stem cell (SC) function and carcinogenesis is poorly understood. The transcription factor Runx1 is known to regulate proliferation in mouse epithelial hair follicle (HF) SCs in vivo and in several mouse and human epithelial cancers. We found a novel sub-set of in vivo Runx1 HFSC target genes related to lip...
Article
Full-text available
Fatty acids are among the most studied nutrients in human metabolism and health. Endogenous fatty acid status influences health and disease via multiple mechanisms at all stages of the life cycle. Despite widespread interest, attempts to summarize the results of multiple studies addressing similar fatty acid-related outcomes via meta-analyses and s...
Article
Introduction: The only known non-pharmacological means to alter long chain polyunsaturated fatty acid (LCPUFA) abundance in mammalian tissue is by altering substrate fatty acid ratios. Alternative mRNA splicing is increasingly recognized as a modulator of protein structure and function. Here we report identification of a novel alternative transcri...
Article
Full-text available
Vernix caseosa, the white waxy coating found on newborn human skin, is thought to be a uniquely human substance. Its signature characteristic is exceptional richness in saturated branched chain fatty acids (BCFA) and squalene. Vernix particles sloughed from the skin suspended in amniotic fluid are swallowed by the human fetus, depositing BCFA/squal...
Article
Background: Arachidonic acid (AA) is the major polyunsaturated fatty acid (PUFA) substrate for potent eicosanoid signaling to modulate inflammation and thrombosis and is controlled in part by tissue abundance. Fatty acid desaturase 1 (FADS1) catalyzes synthesis of omega-6 (n-3) AA and n-3 eicosapentaenoic acid (EPA). The rs66698963 polymorphism, a...
Data
Oligos used to generate L. reuteri mutants.
Data
L. reuteri strains isolated from various hosts. Host, strain name, country of origin, clade, and site of isolation on the human body (if applicable) are given.
Data
Filtered and unfiltered mutations in the L. reuteri in vitro population and HF diet isolate sequencing data. Tab ‘Key’ describes the information in the subsequent tabs. Tab ‘All’ shows all variants passing filtering by GATK. Tab ‘Filtered’ shows variants filtered to exclude alleles in genes annotated with ‘mobile element protein’, ‘transposase’, ‘p...
Data
Filtered and unfiltered mutations in the L. johnsonii in vitro population sequencing data. Tabs and details are the same as for Supplementary file 3.
Data
Lactobacilli in vitro population sequencing. Tab ‘SequencingCoverage’ gives information on the sequencing run, barcode, number of sequences obtained, and estimated genomic coverage. Tab ‘AncestorGenomes’ gives information on the assembled LJ0 and LR0 genomes.
Data
RAST annotation for the assembled LR0 genome.
Data
RAST annotation for the assembled LJ0 genome.
Preprint
Over the past century, soybean oil (SBO) consumption in the United States increased dramatically. The main SBO fatty acid, linoleic acid (18:2), inhibits in vitro the growth of lactobacilli, beneficial members of the small intestinal microbiota. Human-associated lactobacilli have declined in prevalence in Western microbiomes, but how dietary change...
Article
Full-text available
Over the past century, soybean oil (SBO) consumption in the United States increased dramatically. The main SBO fatty acid, linoleic acid (18:2), inhibits in vitro the growth of lactobacilli, beneficial members of the small intestinal microbiota. Human-associated lactobacilli have declined in prevalence in Western microbiomes, but how dietary change...
Article
Sports doping requires high precision carbon isotope ratio (CIR) analysis of endogenous steroids using gas chromatography-combustion isotope ratio mass spectrometry (GCC-IRMS), however methods are relatively slow and cumbersome. A cryofocusing fast GCC-IRMS (Cryofocus Fast GCC-IRMS) was developed and optimized with minimal peak broadening using a p...
Article
Food availability and quality are both critical for growing young animals. In nature, swallows (Tachycineta bicolor) and other aerial insectivores feed on both aquatic insects, which are rich in omega-3 highly unsaturated fatty acids (HUFA) and terrestrial insects, which contain considerably lower amounts of omega-3 HUFA. Carnivorous mammals and fi...
Article
Background: Excess vernix caseosa produced by the fetal skin appears as particles suspended in the amniotic fluid in late gestation, is swallowed by the fetus and is found throughout the newborn GI tract as the first organisms are arriving to colonize the gut. Lipid rich vernix contains an unusually high 29% branched chain fatty acid (BCFA). BCFA...
Article
High precision carbon isotope ratio analysis of urinary steroids by gas chromatography combustion isotope ratio mass spectrometry (GCC-IRMS) is the official test to detect illicit doping of synthetic versions of endogenous steroids such as testosterone. Our group created the first steroid isotopic standards (SIS) specifically for the World Anti-Dop...