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The Journal of Nutritional Biochemistry Jun 2024Increased adiposity is a significant risk factor for pancreatic cancer development. Multiple preclinical studies have documented that high-fat, high caloric diets, rich...
BACKGROUND
Increased adiposity is a significant risk factor for pancreatic cancer development. Multiple preclinical studies have documented that high-fat, high caloric diets, rich in omega-6 fatty acids (FA) accelerate pancreatic cancer development. However, the effect of a high-fat, low sucrose diet (HFD), on pancreatic carcinogenesis remains unclear. We evaluated the impact of a HFD on early-stage pancreatic carcinogenesis in the clinically relevant Kras; Ptf1a (KC) genetically engineered mouse model, and characterized the role of the mesenteric adipose tissue (MAT).
METHODS
Cohorts of male and female KC mice were randomly assigned to a control diet (CD) or a HFD, matched for FA composition (9:1 of omega-6 FA: omega-3 FA), and fed their diets for eight weeks.
RESULTS
After eight weeks on a HFD, KC mice had significantly higher body weight, fat mass, and serum leptin compared to CD-fed KC mice. Furthermore, a HFD accelerated pancreatic acinar-to-ductal metaplasia (ADM) and proliferation, associated with increased activation of ERK and STAT3, and macrophage infiltration in the pancreas, compared to CD-fed KC mice. Metabolomics analysis of the MAT revealed sex differences between diet groups. In females, a HFD altered metabolites related to FA (α-linolenic acid and linoleic acid) and amino acid metabolism (alanine, aspartate, glutamate). In males, a HFD significantly affected pathways related to alanine, aspartate, glutamate, linoleic acid, and the citric acid cycle.
CONCLUSIONS
A HFD accelerates early pancreatic ADM through multifaceted mechanisms, including effects at the tumor and surrounding MAT. The sex-dependent changes in MAT metabolites could explain some of the sex differences in HFD-induced pancreatic ADM.
PubMed: 38876394
DOI: 10.1016/j.jnutbio.2024.109690 -
The Journal of Nutritional Biochemistry Jun 2024Females have higher docosahexaenoic acid (DHA) levels than males, proposed to be a result of higher DHA synthesis rates from α-linolenic acid (ALA). However, DHA...
Females have higher docosahexaenoic acid (DHA) levels than males, proposed to be a result of higher DHA synthesis rates from α-linolenic acid (ALA). However, DHA synthesis rates are reported to be low, and have not been directly compared between sexes. Here, we apply a new compound specific isotope analysis model to determine n-3 PUFA synthesis rates in male and female mice and assess its potential translation to human populations. Male and female C57BL/6N mice were allocated to one of three 12-week dietary interventions with added ALA, eicosapentaenoic acid (EPA) or DHA. The diets included low carbon-13 (δC)-n-3 PUFA for 4 weeks, followed by high δC-n-3 PUFA for 8 weeks (n=4 per diet, time point, sex). Following the diet switch, blood and tissues were collected at multiple time points, and fatty acid levels and δC were determined and fit to one-phase exponential decay modeling. Hepatic DHA synthesis rates were not different (p>0.05) between sexes. However, n-3 docosapentaenoic acid (DPAn-3) synthesis from dietary EPA was 66% higher (p<0.05) in males compared to females, suggesting higher synthesis downstream of DPAn-3 of females. Estimates of percent conversion of dietary ALA to serum DHA was 0.2%, in line with previous rodent and human estimates, but severely underestimates percent dietary ALA conversion to whole body DHA of 9.5%. Taken together, our data indicates that reports of low human DHA synthesis rates may be inaccurate, with synthesis being much higher than previously believed. Future animal studies and translation of this model to humans are needed for greater understanding of n-3 PUFA synthesis and metabolism, and whether the higher-than-expected ALA-derived DHA can offset dietary DHA recommendations set by health agencies.
PubMed: 38876393
DOI: 10.1016/j.jnutbio.2024.109689 -
Food Science & Nutrition Jun 2024The aim of this study is to combine flaxseed oil (FO), rich in α-linolenic acid (ALA), with Sunite sheep tail fat (STF) through a lipase-catalyzed transesterification...
Lipase-catalyzed interesterification of Sunite sheep tail fat and flaxseed oil provides a fat having a unique fatty acid content and favorable physicochemical and nutritional properties.
The aim of this study is to combine flaxseed oil (FO), rich in α-linolenic acid (ALA), with Sunite sheep tail fat (STF) through a lipase-catalyzed transesterification reaction, in order to produce an edible oil with a fatty acid ratio suitable for human needs. Initially, the optimal conditions for esterification were determined using the Box-Behnken design, with the measurement criterion being the content of ALA at the sn-2 position. The results indicated that the highest content of sn-2 ALA was obtained under the conditions of using 6.8 wt% Lipozyme®RMIM as the catalyst, a reaction temperature of 57°C, a reaction time of 3.3 h, and a substrate mass ratio of 5.6:4.4 for STF and FO. This led to the rapid breaking and recombining of molecular bonds, resulting in the interesterified fat (IF) with the highest content of ALA at the sn-2 position. Comparing STF and FO, IF exhibited excellent fatty acid composition and content. Furthermore, IF had a lower melting point and crystallization temperature compared to STF, and its solid fat content decreased with increasing temperature, completely melting at temperatures above 30°C. Thus, IF is a synthesized fat with excellent properties from both animal and vegetable sources.
PubMed: 38873454
DOI: 10.1002/fsn3.4111 -
Translational Animal Science 2024Information about the full spectrum of metabolites present in porcine colostrum and factors that influence metabolite abundances is still incomplete. Parity number...
Information about the full spectrum of metabolites present in porcine colostrum and factors that influence metabolite abundances is still incomplete. Parity number appears to modulate the concentration of single metabolites in colostrum. This study aimed to 1) characterize the metabolome composition and 2) assess the effect of parity on metabolite profiles in porcine colostrum. Sows ( = 20) were divided into three parity groups: A) sows in parity 1 and 2 ( = 8), B) sows in parity 3 and 4 ( = 6), and C) sows in parity 5 and 6 ( = 6). Colostrum was collected within 12 h after parturition. A total of 125 metabolites were identified using targeted reversed-phase high-performance liquid chromatography-tandem mass spectrometry and anion-exchange chromatography-high resolution mass spectrometry. Gas chromatography additionally identified 19 fatty acids (FAs). Across parities, colostrum was rich in creatine and creatinine, 1,3-dioleyl-2-palmitatoylglycerol, 1,3-dipalmitoyl-2-oleoylglycerol, and sialyllactose. Alterations in colostrum concentrations were found for eight metabolites among parity groups ( < 0.05) but the effects were not linear. For instance, colostrum from parity group C comprised 75.4% more valine but 15.7%, 34.1%, and 47.9% less citric, pyruvic, and pyroglutamic acid, respectively, compared to group A ( < 0.05). By contrast, colostrum from parity group B contained 39.5% more spermidine than from group A ( < 0.05). Of the FAs, C18:1, C16:0, and C18:2 n6 were the main FAs across parities. Parity affected four FAs (C18:3n3, C14:1, C17:0ai, and C17:1), including 43.1% less α-linolenic acid (C18:3n3) in colostrum from parity group C compared to groups A and B ( < 0.05). Signature feature ranking identified 1-stearoyl-2-hydroxy--glycero-3-phosphatidylcholine and the secondary bile acid hyodeoxycholic acid as the most discriminative metabolites, showing a higher variable importance in the projection score in colostrum from parity group A than from groups B and C. Overall, results provided a comprehensive overview about the metabolome composition of sow colostrum. The consequences of the changes in colostrum metabolites with increasing parity for the nutrient supply of the piglets should be investigated in the future. The knowledge gained in this study could be used to optimize feeding strategies for sows.
PubMed: 38863596
DOI: 10.1093/tas/txae062 -
BMC Plant Biology Jun 2024Cytoplasmic male sterility (CMS) has greatly improved the utilization of heterosis in crops due to the absence of functional male gametophyte. The newly developed...
BACKGROUND
Cytoplasmic male sterility (CMS) has greatly improved the utilization of heterosis in crops due to the absence of functional male gametophyte. The newly developed sporophytic D1 type CMS (CMS-D1) rice exhibits unique characteristics compared to the well-known sporophytic CMS-WA line, making it a valuable resource for rice breeding.
RESULTS
In this research, a novel CMS-D1 line named Xingye A (XYA) was established, characterized by small, transparent, and shriveled anthers. Histological and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assays conducted on anthers from XYA and its maintainer line XYB revealed that male sterility in XYA is a result of delayed degradation of tapetal cells and abnormal programmed cell death (PCD) of microspores. Transcriptome analysis of young panicles revealed that differentially expressed genes (DEGs) in XYA, compared to XYB, were significantly enriched in processes related to chromatin structure and nucleosomes during the microspore mother cell (MMC) stage. Conversely, processes associated with sporopollenin biosynthesis, pollen exine formation, chitinase activity, and pollen wall assembly were enriched during the meiosis stage. Metabolome analysis identified 176 specific differentially accumulated metabolites (DAMs) during the meiosis stage, enriched in pathways such as α-linoleic acid metabolism, flavone and flavonol biosynthesis, and linolenic acid metabolism. Integration of transcriptomic and metabolomic data underscored the jasmonic acid (JA) biosynthesis pathway was significant enriched in XYA during the meiosis stage compared to XYB. Furthermore, levels of JA, MeJA, OPC4, OPDA, and JA-Ile were all higher in XYA than in XYB at the meiosis stage.
CONCLUSIONS
These findings emphasize the involvement of the JA biosynthetic pathway in pollen development in the CMS-D1 line, providing a foundation for further exploration of the molecular mechanisms involved in CMS-D1 sterility.
Topics: Oryza; Pollen; Plant Infertility; Transcriptome; Gene Expression Profiling; Metabolomics; Metabolome; Gene Expression Regulation, Plant; Meiosis
PubMed: 38862889
DOI: 10.1186/s12870-024-05259-2 -
Heliyon Jun 2024Linseed is a valuable oilseed crop with huge therapeutic importance due to its high content of omega-3 fatty acids in the form of Alpha-linolenic acid (ALA). It is a...
Linseed is a valuable oilseed crop with huge therapeutic importance due to its high content of omega-3 fatty acids in the form of Alpha-linolenic acid (ALA). It is a self-pollinated crop with a low-yielding potential that restricts its improvement endeavors. To overcome low-yielding potential, individual and combination treatments of gamma rays and sodium azide were employed in widely grown linseed varieties. The results revealed a dose-dependent decline in seed germination, seedling height, pollen fertility, chlorophyll, and carotenoid contents and a dose-independent decline in carbonic anhydrase activity. Bio-physiological parameters decreased substantially in combination treatments compared to individual treatments of gamma rays and sodium azide. In contrast, lower doses of gamma rays, sodium azide, and their combinations effectively increased mean values of yield and yield-attributing traits in a few putative mutants. Such putative mutants represent a valuable genetic resource that could be used in future breeding programs for the genetic improvement of linseed and related medicinal plants.
PubMed: 38845881
DOI: 10.1016/j.heliyon.2024.e31329 -
Genes & Nutrition Jun 2024Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are two omega-3 fatty acids that can be synthesized out of their precursor alpha-linolenic acid (ALA). FADS... (Review)
Review
BACKGROUND
Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are two omega-3 fatty acids that can be synthesized out of their precursor alpha-linolenic acid (ALA). FADS and ELOVL genes encode the desaturase and elongase enzymes required for EPA and DHA synthesis from ALA; however, single nucleotide polymorphisms (SNPs) in FADS and ELOVL genes could modify the levels of EPA and DHA synthesized from ALA although there is no consensus in this area. This review aims to investigate EPA and DHA circulating levels in human blood and their association with FADS or ELOVL.
METHODS
PubMed, Cochrane, and Scopus databases were used to identify research articles. They were subsequently reviewed by two independent investigators.
RESULTS
Initially, 353 papers were identified. After removing duplicates and articles not meeting inclusion criteria, 98 full text papers were screened. Finally, this review included 40 studies investigating FADS and/or ELOVL polymorphisms. A total of 47 different SNPs in FADS genes were reported. FADS1 rs174537, rs174547, rs174556 and rs174561 were the most studied SNPs, with minor allele carriers having lower levels of EPA and DHA. SNPs in the FADS genes were in high linkage disequilibrium. SNPs in FADS were correlated with levels of EPA and DHA. No conclusion could be drawn with the ELOVL polymorphisms since the number of studies was too low.
CONCLUSION
Specific SNPs in FADS gene, such as rs174537, have strong associations with circulating levels of EPA and DHA. Continued investigation regarding the impact of genetic variants related to EPA and DHA synthesis is warranted.
PubMed: 38844860
DOI: 10.1186/s12263-024-00747-4 -
Frontiers in Cellular and Infection... 2024Intestinal bacteria metabolize dietary substances to produce bioactive postbiotics, among which some are recognized for their role in promoting host health. We here...
Intestinal bacteria metabolize dietary substances to produce bioactive postbiotics, among which some are recognized for their role in promoting host health. We here explored the postbiotic potential of two omega-3 α-linolenic acid-derived metabolites: -10--15-octadecadienoic acid (t10,c15-18:2) and -9--15-octadecadienoic acid (c9,c15-18:2). Dietary intake of lipids rich in omega-3 α-linolenic acid elevated levels of t10,c15-18:2 and c9,c15-18:2 in the serum and feces of mice, an effect dependent on the presence of intestinal bacteria. Notably, t10,c15-18:2 mitigated skin inflammation in mice that became hypersensitive after exposure to 2,4-dinitrofluorobenzene, an experimental model for allergic contact dermatitis. In particular, t10,c15-18:2-but not c9,c15-18:2-attenuated ear swelling and edema, characteristic symptoms of contact hypersensitivity. The anti-inflammatory effects of t10,c15-18:2 were due to its ability to suppress the release of vascular endothelial growth factor A from keratinocytes, thereby mitigating the enhanced vascular permeability induced by hapten stimulation. Our study identified retinoid X receptor as a functional receptor that mediates the downregulation of skin inflammation upon treatment with t10,c15-18:2. Our results suggest that t10,c15-18:2 holds promise as an omega-3 fatty acid-derived postbiotic with potential therapeutic implications for alleviating the skin edema seen in allergic contact dermatitis-induced inflammation.
Topics: Animals; Mice; Vascular Endothelial Growth Factor A; Fatty Acids, Omega-3; Down-Regulation; Disease Models, Animal; Dermatitis, Contact; Dinitrofluorobenzene; Skin; Keratinocytes; Female; Dermatitis, Allergic Contact; Humans; Gastrointestinal Microbiome; Feces
PubMed: 38841110
DOI: 10.3389/fcimb.2024.1355679 -
Journal of Dairy Science May 2024Probiotics are increasingly used as starter cultures to produce fermented dairy products; however, few studies have investigated the role of probiotics in milk...
Probiotics are increasingly used as starter cultures to produce fermented dairy products; however, few studies have investigated the role of probiotics in milk fermentation metabolism. The current study aimed to investigate whether adding Bifidobacterium animalis ssp. lactis Probio-M8 (Probio-M8) as a starter culture strain could improve milk fermentation by comparing the physico-chemical characteristics and metabolomes of fermented milks produced by a commercial starter culture with and without Probio-M8. Our results showed that adding Probio-M8 shortened the milk fermentation time and improved the fermented milk texture and stability. Metabolomics analyses revealed that adding Probio-M8 affected mostly organic acid, amino acid, and fatty acid metabolism in milk fermentation. Targeted quantitative analyses revealed significant increases in various metabolites related to the sensory quality, nutritive value, and health benefits of the probiotic fermented milk, including 5 organic acids (acetic acid, lactic acid, citric acid, succinic acid, and tartaric acid), 5 essential amino acids (valine, arginine, leucine, isoleucine, and lysine), glutamic acid, and 2 essential fatty acids (α-linolenic acid and docosahexaenoic acid). Thus, applying probiotics in milk fermentation is desirable. This study has generated useful information for developing novel functional dairy products.
PubMed: 38825144
DOI: 10.3168/jds.2024-24863 -
Scientific Reports May 2024Pulmonary arterial hypertension (PAH) is a fatal disease featured by high morbidity and mortality. Although Cordycepin is known for its anti-inflammatory, antioxidant...
Pulmonary arterial hypertension (PAH) is a fatal disease featured by high morbidity and mortality. Although Cordycepin is known for its anti-inflammatory, antioxidant and immune-enhancing effects, its role in PAH treatment and the underlying mechanisms remain unclear. The therapeutic effects of Cordycepin on rats with PAH were investigated using a monocrotaline (MCT)-induced rat model. The metabolic effects of Cordycepin were assessed based on the plasma metabolome. The potential mechanisms of Cordycepin in PAH treatment were investigated through transcriptome sequencing and validated in pulmonary artery smooth muscle cells (PASMC). Evaluations included hematoxylin and eosin staining for pulmonary vascular remodeling, CCK-8 assay, EDU, and TUNEL kits for cell viability, proliferation, and apoptosis, respectively, and western blot for protein expression. Cordycepin significantly reduced right ventricular systolic pressure (RVSP) and right ventricular hypertrophy index (RVHI) in PAH rats, and mitigated pulmonary vascular remodeling. Plasma metabolomics showed that Cordycepin could reverse the metabolic disorders in the lungs of MCT-induced PAH rats, particularly impacting linoleic acid and alpha-linolenic acid metabolism pathways. Transcriptomics revealed that the P53 pathway might be the primary pathway involved, and western blot results showed that Cordycepin significantly increased P53 and P21 protein levels in lung tissues. Integrated analysis of transcriptomics and metabolomics suggested that these pathways were mainly enriched in linoleic acid metabolism and alpha-linolenic acid metabolism pathway. In vitro experiments demonstrated that Cordycepin significantly inhibited the PDGFBB (PD)-induced abnormal proliferation and migration of PASMC and promoted PD-induced apoptosis. Meanwhile, Cordycepin enhanced the expression levels of P53 and P21 proteins in PD-insulted PASMC. However, inhibitors of P53 and P21 eliminated these effects of Cordycepin. Cordycepin may activate the P53-P21 pathway to inhibit abnormal proliferation and migration of PASMC and promote apoptosis, offering a potential approach for PAH treatment.
Topics: Animals; Deoxyadenosines; Rats; Male; Apoptosis; Pulmonary Arterial Hypertension; Cell Proliferation; Transcriptome; Metabolomics; Myocytes, Smooth Muscle; Monocrotaline; Pulmonary Artery; Rats, Sprague-Dawley; Disease Models, Animal; Vascular Remodeling; Tumor Suppressor Protein p53; Linoleic Acid; Hypertrophy, Right Ventricular; Gene Expression Profiling
PubMed: 38816406
DOI: 10.1038/s41598-024-62163-3