Differential utilization of vitamin B12-dependent and independent pathways for propionate metabolism across human cells.

Propionic acid links the oxidation of branched-chain amino acids and odd-chain fatty acids to the TCA cycle. Gut microbes ferment complex fiber remnants, generating high concentrations of short chain fatty acids, acetate, propionate and butyrate, which are shared with the host as fuel sources. Analysis of vitamin B12-dependent propionate utilization in skin biopsy samples has been used to characterize and diagnose underlying inborn errors of cobalamin (or B12) metabolism. In these cells, the B12-dependent enzyme, methylmalonyl-CoA mutase (MMUT), plays a central role in funneling propionate to the TCA cycle intermediate, succinate. Our understanding of the fate of propionate in other cell types, specifically, the involvement of the ß-oxidation-like and methylcitrate pathways, is limited. In this study, we have used [14C]-propionate tracing in combination with genetic ablation or inhibition of MMUT, to reveal the differential utilization of the B12-dependent and independent pathways for propionate metabolism in fibroblast versus colon cell lines. We demonstrate that itaconate can be used as a tool to investigate MMUT-dependent propionate metabolism in cultured cell lines. While MMUT gates the entry of propionate carbons into the TCA cycle in fibroblasts, colon-derived cell lines exhibit a quantitatively significant or exclusive reliance on the ß-oxidation-like pathway. Lipidomics and metabolomics analyses reveal that propionate elicits pleiotropic changes, including an increase in odd-chain glycerophospholipids, and perturbations in the purine nucleotide cycle and arginine/nitric oxide metabolism. The metabolic rationale and the regulatory mechanisms underlying the differential reliance on propionate utilization pathways at a cellular, and possibly tissue level, warrant further elucidation.

Dietary habits and plasma lipid concentrations in a general Japanese population.

INTRODUCTION: Accumulating data on the associations between food consumption and lipid composition in the body is essential for understanding the effects of dietary habits on health. OBJECTIVES: As part of omics research in the Tohoku Medical Megabank Community-Based Cohort Study, this study sought to reveal the dietary impact on plasma lipid concentration in a Japanese population. METHODS: We conducted a correlation analysis of food consumption and plasma lipid concentrations measured using mass spectrometry, for 4032 participants in Miyagi Prefecture, Japan. RESULTS: Our analysis revealed 83 marked correlations between six food categories and the concentrations of plasma lipids in nine subclasses. Previously reported associations, including those between seafood consumption and omega-3 fatty acids, were validated, while those between dairy product consumption and odd-carbon-number fatty acids (odd-FAs) were validated for the first time in an Asian population. Further analysis suggested that dairy product consumption is associated with odd-FAs via sphingomyelin (SM), which suggests that SM is a carrier of odd-FAs. These results are important for understanding odd-FA metabolism with regards to dairy product consumption. CONCLUSION: This study provides insight into the dietary impact on plasma lipid concentration in a Japanese population.

Engineering propionyl-CoA pools for de novo biosynthesis of odd-chain fatty acids in microbial cell factories.

Odd-chain fatty acids (OcFAs) and their derivatives have attracted great interest due to their wide applications in the food, pharmaceutical and petrochemical industries. Microorganisms can naturally de novo produce fatty acids (FAs), where mainly, even-chain with acetyl-CoA instead of odd-chain with propionyl-CoA is used as the primer. Usually, the absence of the precursor propionyl-CoA is considered the main reason that limits the efficient production of OcFAs. It is thus crucial to explore/evaluate/identify promising propionyl-CoA biosynthetic pathways to achieve large-scale biosynthesis of OcFAs. This review discusses the latest advances in microbial metabolism engineering toward producing propionyl-CoA and considers future research directions and challenges toward optimized production of OcFAs.

De novo bio-production of odd-chain fatty acids in Saccharomyces cerevisiae through a synthetic pathway via 3-hydroxypropionic acid.

Odd-chain fatty acids (OCFAs) and their derivatives have attracted increasing attention due to their wide applications in the chemical, fuel, and pharmaceutical industry. However, most natural fatty acids are even-chained, and OCFAs are rare. In this work, a novel pathway was designed and established for de novo synthesis of OCFAs via 3-hydroxypropionic acid (3-HP) as the intermediate in Saccharomyces cerevisiae. First, the OCFAs biosynthesis pathway from 3-HP was confirmed, followed by an optimization of the precursor 3-HP. After combining these strategies, a de novo production of OCFAs at 74.8 mg/L was achieved, and the percentage of OCFAs in total lipids reached 20.3%, reaching the highest ratio of de novo-produced OCFAs. Of the OCFAs produced by the engineered strain, heptadecenoic acid (C17:1) and heptadecanoic acid (C17:0) accounted for 12.1% and 7.6% in total lipid content, respectively. This work provides a new and promising pathway for the de novo bio-production of OCFAs.

Microbial production of odd-chain fatty acids.

Odd-chain fatty acids (OcFAs) and their derivatives have attracted much attention due to their beneficial physiological effects and their potential to be alternatives to advanced fuels. However, cells naturally produce even-chain fatty acids (EcFAs) with negligible OcFAs. In the process of biosynthesis of fatty acids (FAs), the acetyl-CoA serves as the starter unit for EcFAs, and propionyl-CoA works as the starter unit for OcFAs. The lack of sufficient propionyl-CoA, the precursor, is usually regarded as the main restriction for large-scale bioproduction of OcFAs. In recent years, synthetic biology strategies have been used to modify several microorganisms to produce more propionyl-CoA that would enable an efficient biosynthesis of OcFAs. This review discusses several reported and potential metabolic pathways for propionyl-CoA biosynthesis, followed by advances in engineering several cell factories for OcFAs production. Finally, trends and challenges of synthetic biology driven OcFAs production are discussed.

Genetic inactivation of the Carnitine/Acetyl-Carnitine mitochondrial carrier of Yarrowia lipolytica leads to enhanced odd-chain fatty acid production.

BACKGROUND: Mitochondrial carriers (MCs) can deeply affect the intracellular flux distribution of metabolic pathways. The manipulation of their expression level, to redirect the flux toward the production of a molecule of interest, is an attractive target for the metabolic engineering of eukaryotic microorganisms. The non-conventional yeast Yarrowia lipolytica is able to use a wide range of substrates. As oleaginous yeast, it directs most of the acetyl-CoA therefrom generated towards the synthesis of lipids, which occurs in the cytoplasm. Among them, the odd-chain fatty acids (OCFAs) are promising microbial-based compounds with several applications in the medical, cosmetic, chemical and agricultural industries. RESULTS: In this study, we have identified the MC involved in the Carnitine/Acetyl-Carnitine shuttle in Y. lipolytica, YlCrc1. The Y. lipolytica Ylcrc1 knock-out strain failed to grow on ethanol, acetate and oleic acid, demonstrating the fundamental role of this MC in the transport of acetyl-CoA from peroxisomes and cytoplasm into mitochondria. A metabolic engineering strategy involving the deletion of YlCRC1, and the recombinant expression of propionyl-CoA transferase from Ralstonia eutropha (RePCT), improved propionate utilization and its conversion into OCFAs. These genetic modifications and a lipogenic medium supplemented with glucose and propionate as the sole carbon sources, led to enhanced accumulation of OCFAs in Y. lipolytica. CONCLUSIONS: The Carnitine/Acetyl-Carnitine shuttle of Y. lipolytica involving YlCrc1, is the sole pathway for transporting peroxisomal or cytosolic acetyl-CoA to mitochondria. Manipulation of this carrier can be a promising target for metabolic engineering approaches involving cytosolic acetyl-CoA, as demonstrated by the effect of YlCRC1 deletion on OCFAs synthesis.

Associations of Region and Lactation Stage with Odd-Chain Fatty Acid Profile in Triglycerides of Breast Milk in China.

Odd-chain fatty acids (OCFAs), with potential value for growing infants, have been reported in breast milk. The association of location and lactation stage with the profile and content of OCFAs in breast milk was studied. We analyzed 1487 breast milk samples collected from 12 areas in China, and 102 infant formulas from different brands were purchased from the local supermarket. The content of sn-2 C15:0 significantly decreased from the colostrum to the mature stage, while that of C17:0 was not significantly increased by the lactation stage (p > 0.05). The content of C15:0 and C17:0 significantly decreased dramatically after the colostrum period, while the content of C13:0 was highest in the mature stage. The level of C15:0 and C17:0 in human milk from Gansu and Xinjiang was significantly higher than that from other areas. Similar trends were observed on the level of sn-2 C15:0 and C17:0, whereas the content of sn-2 C11:0 and C13:0 was significantly higher in breast milk from Shandong. Based on the PDS-LA analysis, the difference among infant formulas, each stage of human milk and human milk from different locations were different. Research is needed to determine if there are health benefits associated with OCFAs.

Fatty acid composition of the methylotrophic yeast Komagataella phaffii grown under low- and high-methanol conditions.

In this study, we analysed the intracellular fatty acid profiles of Komagataella phaffii during methylotrophic growth. K. phaffii grown on methanol had significantly lower total fatty acid contents in the cells compared with glucose-grown cells. C18 and C16 fatty acids were the predominant fatty acids in K. phaffii, although the contents of odd-chain fatty acids such as C17 fatty acids were also relatively high. Moreover, the intracellular fatty acid composition of K. phaffii changed in response to not only carbon sources but also methanol concentrations: C17 fatty acids and C18:2 content increased significantly as methanol concentration increased, whereas C18:1 and C18:3 contents were significantly lower in methanol-grown cells. The intracellular content of unidentified compounds (Cn H2n O4 ), on the other hand, was significantly greater in cells grown on methanol. As the intracellular contents of these Cn H2n O4 compounds were significantly higher in a gene-disrupted strain for glutathione peroxidase (gpx1Δ) than in the wild-type strain, we presume that the Cn H2n O4 compounds are fatty acid peroxides. These results indicate that K. phaffii can coordinate intracellular fatty acid composition during methylotrophic growth in order to adapt to high-methanol conditions and that certain fatty acid species such as C17:0, C17:1, C17:2 and C18:2 may be related to the physiological functions by which K. phaffii adapts to high-methanol conditions.

Plasma fatty acids and kidney function decline in post-myocardial infarction patients of the Alpha Omega Cohort.

BACKGROUND AND AIMS: Age-related kidney function decline is accelerated in patients with coronary heart disease (CHD). CHD and chronic kidney disease may share common etiologies. We examined plasma fatty acids (FAs) as novel biomarkers of kidney function decline after myocardial infarction (MI). METHODS AND RESULTS: The analysis included 2329 Dutch post-MI patients aged 60-80y (Alpha Omega Cohort) most receiving state-of-the-art medications. Plasma FAs (% total FAs) in cholesteryl esters were assessed at baseline (2002-2006), and ∼40 months change in creatinine-cystatin C based glomerular filtration rate was estimated (eGFR, in ml/min per 1.73 m2). Beta coefficients for annual eGFR change in relation to plasma linoleic acid (LA; 50.1% of total FAs in CE), omega-3 FAs (EPA + DHA; 1.7%), odd-chain FAs (C15:0 and C17:0; 0.2%), and C14:0 (0.7%) were obtained from linear regression analyses adjusted for age, sex, smoking, and alcohol intake. Mean baseline eGFR ±SD was 78.5 ± 18.7, which declined by 4.7 ± 13.1 during follow-up, or 1.4 ± 3.9 per year. The annual decline in eGFR was less in patients with higher plasma LA (adjusted beta: 0.40 for LA >47 vs ≤ 47%, 95% CI: 0.01; 0.78; p = 0.046). Associations of plasma LA with annual eGFR decline were stronger in 437 patients with diabetes (1.21, 0.24; 2.19) and in 402 patients with CKD (eGFR<60; 0.90, -0.09; 1.89). Weaker, non-significant associations with kidney function decline were observed for the other plasma FAs. CONCLUSION: Higher plasma LA may be a good predictor of less kidney function decline after MI, particularly in patients with diabetes. The Alpha Omega Cohort is registered with clinicaltrials.gov, NCT03192410.

Dietary protein insufficiency: an important consideration in fatty liver disease?

Dietary protein insufficiency has been linked to excessive TAG storage and non-alcoholic fatty liver disease (NAFLD) in developing countries. Hepatic TAG accumulation following a low-protein diet may be due to altered peroxisomal, mitochondrial and gut microbiota function. Hepatic peroxisomes and mitochondria normally mediate metabolism of nutrients to provide energy and substrates for lipogenesis. Peroxisome biogenesis and activities can be modulated by odd-chain fatty acids (OCFA) and SCFA that are derived from gut bacteria, for example, propionate and butyrate. Also produced during amino acid metabolism by peroxisomes and mitochondria, propionate and butyrate concentrations correlate inversely with risk of obesity, insulin resistance and NAFLD. In this horizon-scanning review, we have compiled available evidence on the effects of protein malnutrition on OCFA production, arising from loss in mitochondrial, peroxisomal and gut microbiota function, and its association with lipid accumulation in the liver. The methyl donor amino acid composition of dietary protein is an important contributor to liver function and lipid storage; the presence and abundance of dietary branched-chain amino acids can modulate the composition and metabolic activity of the gut microbiome and, on the other hand, can affect protective OCFA and SCFA production in the liver. In preclinical animal models fed with low-protein diets, specific amino acid supplementation can ameliorate fatty liver disease. The association between low dietary protein intake and fatty liver disease is underexplored and merits further investigation, particularly in vulnerable groups with dietary protein restriction in developing countries.

Differences in the lipid patterns during maturation of 3T3-L1 adipocytes investigated by thin-layer chromatography, gas chromatography, and mass spectrometric approaches.

Populations of industrialized countries have registered a dramatically increasing prevalence in obesity for many years. Despite continuous research, mechanisms involved in the storage and utilization of chemical energy in adipocytes are still under investigation. Adipocytes have the task to store excessive energy in the form of triacylglycerols (TG) and it is already well-known that the fatty acyl composition of TG is largely determined by the composition of the diet. In contrast to TG, the composition of adipocyte phospholipids was less comprehensively investigated. In this study, the compositions of the most abundant phospholipid classes of 3T3-L1 undifferentiated (preadipocytes) and differentiated cells (adipocytes) were determined. The lipid fractions were isolated by normal phase high-performance thin-layer chromatography and subsequently analyzed by electrospray ionization mass spectrometry. Additionally, the fatty acyl (FA) compositions were determined by gas chromatography. The positions of the FA residues were additionally confirmed by phospholipase A2 digestion. The advantages and disadvantages of the different analytical approaches will be discussed. It will be shown that undifferentiated 3T3-L1 and mature adipocytes differ extremely regarding their compositions. This goes along with an increase in odd-chain fatty acids. Graphical abstract.

Inclusion of Soluble Fiber in the Gestation Diet Changes the Gut Microbiota, Affects Plasma Propionate and Odd-Chain Fatty Acids Levels, and Improves Insulin Sensitivity in Sows.

The transition from pregnancy to lactation is characterized by a progressive decrease in insulin sensitivity. Propionate increases with dietary fiber consumption and has been shown to improve insulin sensitivity. Recent studies suggest that plasma odd-chain fatty acids [OCFAs; pentadecanoic acid (C15:0) and heptadecanoic acid (C17:0)] that inversely correlated with insulin resistance are synthesized endogenously from gut-derived propionate. The present study investigated the effects of soluble fiber during gestation on gut microbiota, plasma non-esterified fatty acids and insulin sensitivity in sows. Sows were allocated to either control or 2.0% guar gum plus pregelatinized waxy maize starch (SF) dietary treatment during gestation. The SF addition changes the structure and composition of gut microbiota in sows. Genus Eubacterium increased by SF addition may promote intestinal propionate production. Moreover, the dietary SF increased circulating levels of plasma OCFAs, especially C17:0. The SF-fed sows had a higher insulin sensitivity and a lower systemic inflammation level during perinatal period. Furthermore, the plasma C15:0 and C17:0 was negatively correlated with the area under curve of plasma glucose after meal and plasma interleukin-6. In conclusion, dietary SF improves insulin sensitivity and alleviates systemic inflammation in perinatal sows, potentially related to its stimulating effect on propionate and OCFAs production.

Microbial synthesis of functional odd-chain fatty acids: a review.

Odd-chain fatty acids (OCFAs) naturally occur in bacteria, higher animals, and in plants. During recent years, they have received increasing attention due to their unique pharmacological properties and usefulness for agricultural and industrial applications. Recently, OCFAs have been identified and quantified in a few organisms, and new pharmacological functions of OCFAs have been reported. Some of the publications are related to the optimization of OCFA production through fermentation and genetic engineering. The present review aims to provide a summary on the recent progress in the field of microbial-derived OCFAs. More specifically, we outline the publications of OCFAs related to (i) different sources of OCFAs; (ii) endogenous synthesis of OCFAs; (iii) production of OCFAs through fermentation; (iv) genetic engineering related to OCFA; and (v) role of OCFAs in human health and disease. Finally, some areas that require further research are discussed.

Dairy Products, Dairy Fatty Acids, and the Prevention of Cardiometabolic Disease: a Review of Recent Evidence.

PURPOSE OF REVIEW: To examine recent literature on dairy products, dairy fatty acids, and cardiometabolic disease. Primary questions of interest include what unique challenges researchers face when investigating dairy products/biomarkers, whether one should consume dairy to reduce disease risk, whether dairy fatty acids may be beneficial for health, and whether one should prefer low- or high-fat dairy products. RECENT FINDINGS: Dairy composes about 10% of the calories in a typical American diet, about half of that coming from fluid milk, half coming from cheese, and small amounts from yogurt. Most meta-analyses report no or weak inverse association between dairy intake with cardiovascular disease and related intermediate outcomes. There is some suggestion that dairy consumption was inversely associated with stroke incidence and yogurt consumption was associated with lower risk of type 2 diabetes. Odd chain fatty acids (OCFAs) found primarily in dairy (15:0 and 17:0) appear to be inversely associated with cardiometabolic risk, but causation is uncertain. Substitution analyses based on prospective cohorts suggested that replacing dairy fat with vegetable fat or polyunsaturated fat was associated with significantly lower risk of cardiovascular disease. Current evidence suggests null or weak inverse association between consumption of dairy products and risk of cardiovascular disease. However, replacing dairy fat with polyunsaturated fat, especially from plant-based foods, may confer health benefits. More research is needed to examine health effects of different types of dairy products in diverse populations.

Metabolic perturbations associated with the consumption of a ketogenic medium-chain TAG diet in dogs with idiopathic epilepsy.

Consumption of diets containing medium-chain TAG (MCT) has been shown to confer neuroprotective effects. We aim to identify the global metabolic perturbations associated with consumption of a ketogenic diet (medium-chain TAG diet (MCTD)) in dogs with idiopathic epilepsy. We used ultra-performance liquid chromatography-MS (UPLC-MS) to generate metabolic and lipidomic profiles of fasted canine serum and made comparisons between the MCTD and standardised placebo diet phases. We identified metabolites that differed significantly between diet phases using metabolite fragmentation profiles generated by tandem MS (UPLC-MS/MS). Consumption of the MCTD resulted in significant differences in serum metabolic profiles when compared with the placebo diet, where sixteen altered lipid metabolites were identified. Consumption of the MCTD resulted in reduced abundances of palmitoylcarnitine, octadecenoylcarnitine, stearoylcarnitine and significant changes, both reduced and increased abundances, of phosphatidylcholine (PC) metabolites. There was a significant increase in abundance of the saturated C17 : 0 fatty acyl moieties during the MCTD phase. Lysophosphatidylcholine (17 : 0) (P=0·01) and PC (17:0/20:4) (P=0·03) were both significantly higher in abundance during the MCTD. The data presented in this study highlight global changes in lipid metabolism, and, of particular interest, in the C17 : 0 moieties, as a result of MCT consumption. Elucidating the global metabolic response of MCT consumption will not only improve the administration of current ketogenic diets for neurological disease models but also provides new avenues for research to develop better diet therapies with improved neuroprotective efficacies. Future studies should clarify the involvement and importance of C17 : 0 moieties in endogenous MCT metabolic pathways.

Candida albicans utilizes a modified ß-oxidation pathway for the degradation of toxic propionyl-CoA.

Propionyl-CoA arises as a metabolic intermediate from the degradation of propionate, odd-chain fatty acids, and some amino acids. Thus, pathways for catabolism of this intermediate have evolved in all kingdoms of life, preventing the accumulation of toxic propionyl-CoA concentrations. Previous studies have shown that fungi generally use the methyl citrate cycle for propionyl-CoA degradation. Here, we show that this is not the case for the pathogenic fungus Candida albicans despite its ability to use propionate and valerate as carbon sources. Comparative proteome analyses suggested the presence of a modified ß-oxidation pathway with the key intermediate 3-hydroxypropionate. Gene deletion analyses confirmed that the enoyl-CoA hydratase/dehydrogenase Fox2p, the putative 3-hydroxypropionyl-CoA hydrolase Ehd3p, the 3-hydroxypropionate dehydrogenase Hpd1p, and the putative malonate semialdehyde dehydrogenase Ald6p essentially contribute to propionyl-CoA degradation and its conversion to acetyl-CoA. The function of Hpd1p was further supported by the detection of accumulating 3-hydroxypropionate in the hpd1 mutant on propionyl-CoA-generating nutrients. Substrate specificity of Hpd1p was determined from recombinant purified enzyme, which revealed a preference for 3-hydroxypropionate, although serine and 3-hydroxyisobutyrate could also serve as substrates. Finally, virulence studies in a murine sepsis model revealed attenuated virulence of the hpd1 mutant, which indicates generation of propionyl-CoA from host-provided nutrients during infection.

Heptadecanoic Acid, an Odd-Chain Fatty Acid, Induces Apoptosis and Enhances Gemcitabine Chemosensitivity in Pancreatic Cancer Cells.

Odd-chain saturated fatty acids generally serve as specific biomarkers of dietary components and dairy intake, some of which have anticancer properties. This study was performed to assess the anticancer effects of heptadecanoic acid (HDNA) in human pancreatic carcinoma cells. MTT (thiazolyl blue tetrazolium bromide) assay showed that HDNA exerted stronger cytotoxic effects than pentadecanoic acid, palmitic acid (16:0), stearic acid (18:0), oleic acid (18:1), and linoleic acid (18:2) on both Panc-1 and MIA PaCa-2 pancreatic cancer cells. In addition, HDNA reduced colony formation and induced apoptosis in these pancreatic cancer cells as indicated by Hoechst 33342 staining, Annexin V/propidium iodide staining, cell cycle analysis, and Western blotting analysis in a dose-dependent manner. Moreover, HDNA synergistically reduced cell viability and promoted apoptosis when combined with gemcitabine (GEM), a chemotherapeutic agent commonly used in the treatment of pancreatic cancer. GEM-resistant MIA PaCa-2 (GR-MIA PaCa-2) cells with a resistance indices (RI) value of 215.09 [RI = half-maximal inhibitory concentration (IC50) of GR-MIA PaCa-2 cells/IC50 of MIA PaCa-2 cells] were established, and the efficacy of HDNA on GEM chemosensitivity was confirmed. Surprisingly, HDNA exhibited even higher antiproliferative efficacy against GR-MIA PaCa-2 cells (IC50 = 71.45 ± 6.37 µM) than parental MIA PaCa-2 cells (IC50 = 77.47 ± 2.10 µM). Finally, HDNA treatment inhibited the Hippo pathway and induced apoptosis of GR-MIA PaCa-2 cells. These findings suggest the beneficial effects of a HDNA-rich diet during pancreatic cancer treatments.

Efficient Biosynthesis of Odd-Chain Fatty Acids via Regulating the Supply and Consumption of Propionyl-CoA in Schizochytrium sp.

Odd chain fatty acids (OCFAs) are high-value-added compounds with great application in the field of food and medicine. As an oleaginous microorganism, Schizochytrium sp. has the potential to produce OCFAs efficiently. Propionyl-CoA is used as a precursor to synthesize OCFAs through the fatty acid synthetase (FAS) pathway, so its flow direction determines the yield of OCFAs. Here, different substrates were assessed to promote propionyl-CoA supply for OCFA accumulation. Moreover, the methylmalonyl-CoA mutase (MCM) was identified as the key gene responsible for propionyl-CoA consumption, which promotes the propionyl-CoA to enter into the tricarboxylic acid cycle rather than the FAS pathway. As one of the classic B12-dependent enzymes, the activity of MCM can be inhibited in the absence of B12. As expected, the OCFA accumulation was greatly increased. However, the removal of B12 caused growth limitation. Furthermore, the MCM was knocked out to block the consumption of propionyl-CoA and to maintain cell growth; results showed that the engineered strain achieved the OCFAs titer of 2.82 g/L, which is 5.76-fold that of wild type. Last, a fed-batch co-feeding strategy was developed, resulting in the highest reported OCFAs titer of 6.82 g/L. This study provides guidance for the microbial production of OCFAs.

MHP1 and MHL generate odd-chain fatty acids from 2-hydroxy fatty acids in sphingolipids and are related to immunity in Arabidopsis thaliana.

In plants, the 2-hydroxy fatty acids (HFAs) of sphingolipids are important for plant growth and stress responses. Although the synthetic pathway of HFAs is well understood, their degradation has not yet been elucidated. In Saccharomyces cerevisiae, Mpo1 has been identified as a dioxygenase that degrades HFAs. This study examined the functions of two homologs of yeast Mpo1, MHP1 and MHL, in Arabidopsis thaliana. The mhp1 and mhp1mhl mutants showed a dwarf phenotype compared to that of the wild type. Lipid analysis of the mutants revealed the involvement of MHP1 and MHL in synthesizing odd-chain fatty acids (OCFAs), possibly by the degradation of HFAs. OCFAs are present in trace amounts in plants; however, their physiological significance is largely unknown. RNA sequence analysis of the mhp1mhl mutant revealed that growth-related genes decreased, whereas genes involved in stress response increased. Additionally, the mhp1mhl mutant had increased expression of defense-related genes and increased resistance to infection by Pseudomonas syringae pv. tomato DC3000 (Pto), and Pto carrying the effector AvrRpt2. Phytohormone analysis demonstrated that jasmonic acid in mhp1mhl was higher than that in the wild type. These results indicate that MHP1 and MHL are involved in synthesizing OCFAs and immunity in Arabidopsis.

Early Pregnancy Maternal Plasma Phospholipid Saturated Fatty Acids and Fetal Growth: Findings from a Multi-Racial/Ethnic Birth Cohort in US.

Saturated fatty acids (SFAs) during pregnancy are associated with disrupted metabolic programming among offspring at birth and later growth. We examined plasma phospholipid SFAs in early pregnancy and fetal growth throughout pregnancy. We enrolled 321 pregnant women from the NICHD Fetal Growth Studies-Singleton Cohort at gestational weeks 8-13. Ultrasonogram schedules were randomly assigned to capture weekly fetal growth. We measured plasma phospholipid SFAs at early pregnancy using blood samples and modeled fetal growth trajectories across tertiles of SFAs with cubic splines using linear mixed models after full adjustment. We then compared pairwise weekly fetal growth biometrics referencing the lowest tertile in each SFA using the Wald test. We found that even-chain and very long even-chain SFAs were inversely associated, whereas odd-chain SFAs were positively associated with fetal weight and size. Compared with the lowest tertile, the highest tertile of pentadecanoic acid (15:0) had a greater fetal weight and size, starting from week 13 until late pregnancy (at week 39: 3429.89 vs. 3269.08 g for estimated fetal weight; 328.14 vs. 323.00 mm for head circumference). Our findings could inspire future interventions using an alternative high-fat diet rich in odd-chain SFAs for optimal fetal growth.