Palmitic acid (PA) is a risk factor for atherosclerosis but its significance in premature coronary artery disease (PCAD) remains poorly understood. Herein, we investigated the impact of circulating PA levels on the risk of PCAD occurrence in Chinese patients.

In this case control study, we included patients diagnosed with PCAD and age-matched non-CAD controls between June 2022 and December 2023. Participants' serum PA levels were quantified using ultra-performance liquid chromatography-mass spectrometry, and correlations with PCAD were determined using R (v4.2.2). The potential mediating effect of low density lipoprotein cholesterol (LDL-C) for the association between PA and PACD was also evaluated.

In this study of 393 adults (206 PCAD patients and 187 non-CAD controls), serum PA levels showed significant positive correlations with LDL-C and total cholesterol. Compared to controls, PCAD patients had higher proportions of males, smokers, and diabetics, along with elevated PA, LDL-C, and triglycerides, but reduced HDL-C (all P < 0.05). Elevated serum PA (per 10µmol/L increase, OR = 1.12, 95% CI = 1.05-1.20) was significantly associated with an increased risk of PCAD after adjustment for multivariable factors. Further adjustment for LDL-C levels attenuated, but remained statistically significant, the association between PA and PCAD (per 10µmol/L increase, OR = 1.10, 95% CI = 1.03-1.18). Mediation analysis showed that LDL-C mediated 16% of PA's total effect on PCAD.

Elevated PA circulating levels were found to be related with PCAD risks among Chinese, and increased LDL-C levels could partly mediate this effect.

Diets restricted in carbohydrates may be beneficial for diabetes management. However, without reducing energy intake, carbohydrate restriction results in increased protein and fat intake. Understanding how this macronutrient substitution is associated with adipose tissue distribution is important to prevent diabetes progression. Therefore, the aim was to investigate the isocaloric substitution of carbohydrates with fat and protein in relation to subcutaneous (SAT) and visceral adipose tissue (VAT) and hepatic lipid (HL) content in individuals with recent-onset type 1 (T1D) and type 2 diabetes (T2D), accounting for macronutrient quality.

This cross-sectional analysis includes participants with T1D (n = 137) and T2D (n = 170) from the German Diabetes Study (GDS). Dietary macronutrient intake was derived from dietary information assessed with a validated food frequency questionnaire. SAT and VAT were measured with magnetic resonance (MR) imaging, while HL content with 1H MR spectroscopy. Isocaloric substitution analyses based on multivariable linear regression models were conducted to examine the replacement of total and higher glycemic index (GI) carbohydrates in energy percent (En%) with total fat, monounsaturated (MUFA), polyunsaturated (PUFA), and saturated fatty acids (SFA), and protein in regard to SAT, VAT and HL content.

In individuals with T1D, substituting carbohydrates with total fat was not associated with SAT, while substituting carbohydrates with protein demonstrated higher SAT [β (95% CI) per 5 En%: 3100 cm3 (25, 6200)]. In individuals with T2D, replacing carbohydrates with total fat or protein showed no association with SAT and VAT. However, substituting carbohydrates with PUFA was associated with lower VAT [-970 cm3 (-1900, -40)] and HL content [-3.3% (-6.9, 0.4)], while replacing carbohydrates with SFA was associated with higher HL content [2.4% (-0.6, 5.4)]. Substituting carbohydrates with protein was associated with lower HL content in individuals with T2D [-2.4% (-4.9, 0.0)], mainly driven by plant-based protein. There were no substantial differences between the replacement of total and higher GI carbohydrates.

The quality of substituted nutrients may play an important role for adipose tissue and HL accumulation in individuals with T2D. Particularly, integrating PUFAs and plant-based proteins into the diet seems beneficial for VAT and HL content.

The intestinal development and nutritional needs of piglets after birth are similar to those of human infants.

This study aimed to investigate the effect of different forms of odd-chain fatty acids (OCFAs) on the growth and intestinal morphology and function of milk replacer-fed piglets, as a model for human infants.

Forty 7-d-old piglets from 8 sows were randomly assigned into 5 groups (n = 8, each from a different litter) and fed sow milk or milk replacers supplemented with different kinds of fats (control fats, docosahexaenoic acid algal oil-, OCFA algal oil-, and OCFA-enriched fats) for 21 d. One-way analysis of variance was performed to compare the milk replacer-fed piglet groups, and unpaired t test was used to compare sow milk- and milk replacer-fed piglets.

Milk replacers supplemented with OCFA-enriched fats increased the average daily gain (ADG), ratio of villus height to crypt depth, and protein expression of Ki67, phosphorylated (p)-mTOR, p-S6K1, Occludin, Claudin, and ZO-1 in the selected intestines of piglets and decreased the protein expression of p-ULK1, Parkin, and PINK1 to levels similar to those of the sow milk-fed group (P < 0.05).

Overall, milk replacers supplemented with OCFA-enriched fats improved the ADG and the intestinal morphology and function of piglets to levels comparable to those of the sow milk-fed piglets.

Objective biomarkers of diet, such as metabolomics, may improve dietary assessment and provide additional insight into how diet influences disease risk. The portfolio diet, a cholesterol-lowering plant-based diet, is recommended for lowering low-density lipoprotein cholesterol (LDL-C). This diet is low in saturated fat and includes nuts, plant protein (legumes), viscous fiber, and phytosterols.

We examined metabolomic profiles in response to the portfolio diet in two randomized controlled trials (RCTs), where all foods were provided to the participants, compared to a control vegetarian diet and the same control diet with a statin.

The first RCT included 34 adults (age 58.4 ± 8.6 y) and the second RCT included 25 adults (age 61.0 ± 9.6 y), all with high LDL-C (>4.1 mmol/L). Plasma samples were obtained at baseline, week 2, and week 4 in both RCTs for metabolomics analysis using liquid chromatography-tandem mass spectrometry. Linear mixed models were used to examine effects of the interventions on the metabolites in each RCT, applying a Bonferroni correction.

Of 496 known metabolites, 145 and 63 metabolites significantly changed within the portfolio diet interventions in the first and second RCT, respectively. The majority were glycerophosphocholines (32%), triacylglycerols (20%), glycerophosphoethanolamines (14%), sphingomyelins (8%), and amino acids and peptides (8%) in the first RCT, and glycerophosphocholines (48%), glycerophosphoethanolamines (17%), and amino acids and peptides (8%) in the second RCT. Fifty-two metabolites were consistently changed in the same direction with the portfolio diet intervention across both RCTs, after Bonferroni correction.

Many of these metabolites likely reflect the plant-based nature, low saturated fat content, and cholesterol-lowering effects of the diet, such as increased N2-acetylornithine, L-pipecolic acid, lenticin, and decreased C18:0 lipids and cholesteryl esters. Further research is needed to validate these metabolites as biomarkers of a plant-based dietary pattern.

Pentadecanoic acid (C15:0) is a saturated odd-chain fatty acid (OCFA), mainly found in dairy products. Its physiological and nutritional effects are still unknown, yet some recent evidences suggest it might be beneficial to human health. Moreover, pentadecanoic acid has recently been suspected of having essential roles in humans, although the mechanisms are not described. We therefore questioned the potential essentiality of this fatty acid (FA). We investigated in vivo the effect of a C15:0 supplementation on essential fatty acid (EFA) deficient Wistar rats. Female rats were fed an EFA-deficient diet 2 weeks before mating, during pregnancy and lactation. Weaned pups were fed the EFA-deficient diet or were switched to a diet supplemented with C15:0 or linoleic acid (LA) for 11 weeks. A control group was fed with EFA during the whole study. Since linoleic acid deficiency is known to induce growth delay, weights were measured throughout the experiment and FA content in collected tissues were analyzed to evaluate biochemical markers of the deficiency. As expected, EFA-deficient rats showed growth retardation, compared to control rats. Supplementation of C15:0 at weaning increased early growth rate compared to deficient animals, as also did the supplementation of C18:2 n-6. Furthermore, the supplementation of C15:0 in the diet of EFA-deficient animals induced the previously undescribed synthesis of odd-chain PUFAs of the n-8 family (C19:3, C21:3 and C21:4 n-8). These results suggest dietary C15:0 might counteract EFA induced growth retardation, possibly through the synthesis of odd-chain n-8 PUFAs, yet mechanisms are to be deciphered for further validation.

Odd chain fatty acids (OCFAs) are gaining attention for their valuable medical and nutritional applications. Microbial fermentation offers a sustainable and environmentally friendly alternative for OCFA production compared to traditional extraction or chemical synthesis methods. To achieve an economically feasible OCFA production process, it is essential to identify and develop microbial cell factories capable of producing OCFAs with high titers and yields.

We selected 19 yeast species, including both oleaginous yeasts and representatives from the Ascomycota and Basidiomycota phyla, based on their known or potential ability to produce OCFAs. These species were screened under various growth conditions to evaluate their OCFA production potential. In glucose-based, nitrogen-limited media, the strains produced fatty acids to varying extents, with OCFAs comprising 0.5-5% of the total fatty acids. When using the OCFAs precursor propionic acid as the sole carbon source, only eight strains exhibited growth, with tolerance to propionic acid concentrations between 5 and 29 g/L. The strains also displayed varying efficiencies in converting propionic acid into fatty acids, yielding between 0.16 and 1.22 g/L of fatty acids, with OCFAs constituting 37-89% of total fatty acids. Among the top performing strains, Cutaneotrichosporon oleaginosus produced the highest OCFA titers and yields (0.94 g/L, 0.07 g/g), Yarrowia lipolytica demonstrated superior growth rates even at elevated propionic acid concentrations, and Rhodotorula toruloides achieved the highest proportion of OCFAs relative to total fatty acids (89%).

Our findings highlight the diverse capacities of the selected yeast species for OCFA production, identifying several promising strains for further optimization as microbial cell factories in sustainable OCFA production processes.

Recombinant human growth hormone (rhGH) therapy is the primary treatment for children born small for gestational age (SGA) who fail to show spontaneous catch-up growth by two or four years. While its effects on white adipose tissue are well-documented, this pilot study aimed to investigate its impact on the lipidome and the thermogenic and endocrine activities of brown adipose tissue (BAT) in SGA children following rhGH treatment. The study involved 11 SGA children divided into two groups: (a) SGA children who were not treated with rhGH (n = 4) and (b) SGA children who received rhGH treatment with Saizen® (n = 7). This second group of seven SGA children was followed for 12 months after initiating rhGH treatment. Interventions included 12-hour fasting blood extraction and infrared thermography at baseline and 3 and 12 months post-treatment. Five appropriate-for-gestational-age (AGA) children served as controls. Exclusion criteria included endocrinological, genetic, or chronic diseases. Untargeted lipidomics analysis was performed using liquid chromatography-mass spectrometry (LC-MS), and serum biomarker levels were measured using ELISA assays. Serum lipidomic analysis revealed that free fatty acids (FFAs) increased to levels close to those of the AGA group after three months of rhGH administration, including polyunsaturated fatty acids, correlating with reduced leptin levels. Elevated levels of 1a,1b-dihomo-PGJ2 and adrenic acid suggested potential aging markers. rhGH treatment also significantly reduced meteorin-like (METRNL) and monocyte chemoattractant protein-1 (MCP1) serum levels to control levels. rhGH influences the serum lipidome, promoting changes in maturation and metabolism. Further research is required to clarify the direct effects of rhGH on specific lipid species and batokines, potentially addressing metabolic disturbances linked to obesity and aging.

Shifts in dietary patterns during lifestyle transitions are integral components of the dynamic interactions between humans and their environments. Investigating the link between dietary diversity, the composition of the human lipidome and infection is key to understanding the interplay between diet and susceptibility to pathogens.

Here we address this question by performing a comparative study of two ethnic groups with divergent dietary patterns: Fulani, who are nomad pastoralists with a dairy-centric diet, and Mossi, who are farmers with a plant-based diet. We generate 196 paired global lipidomes (927 lipid molecules) from both groups before and during natural Plasmodium falciparum infection.

Our analysis revealed 211 significantly differentially abundant lipid molecules between the two ethnic groups in both infection states. We show that ethnicity has a greater impact on the lipidome of these children than do P. falciparum infection and report inter-ethnic differences that impact pathogenesis. We highlight elevated levels of pentadecanoic acid (C15:0)-containing phospholipids in Fulani and experimentally demonstrate the suppressive effects of lysophosphatidylcholine LysoPC (15:0) on P. falciparum gametocyte production.

These findings link the Fulani's dairy-centric diet and lower P. falciparum gametocyte densities reported in this group and underscore the intricate links between dietary lipids and the host response to infection.

Osteoarthritis (OA) is linked to disrupted lipid metabolism. We aimed to profile the lipid composition of human articular cartilage, investigate OA-associated lipidome changes, and explore biological effects.

Lipidomic profiling and computational analyses were performed on human articular chondrocytes (hACs) from non-OA (n = 13) and OA (n = 14) hips. Lipid changes were confirmed in the destabilisation of the medial meniscus (DMM) mouse model. The effect of specific lipids was evaluated by in vitro supplementation and gene silencing.

We identified 573 lipid species covering 11 lipid classes in hACs. OA and non-OA hACs showed distinct lipid profiles. Most ceramides and dihydroceramides were increased, while cholesteryl esters, diacylglycerols, triacylglycerols, sphingomyelins, hexosylceramides, and lactosylceramides were predominantly decreased in OA chondrocytes. Most upregulated lipids in OA contained C18:1, C20:4, or C22:4 side chains. Many downregulated lipids contained C18:2 or odd-chain C17:0. Lipid profiling of articular cartilage from the DMM mouse model paralleled changes in OA hACs, including odd-chain C17:0 reduction. Further analysis showed that deficiency in enzyme 2-hydroxyacyl-CoA lyase 1 (HACL1), responsible for odd-chain fatty acid synthesis, leads to accumulation of 2-hydroxy C18:0, precursor of C17:0, which results in a shift in hACs from an anabolic to a catabolic state.

Our study maps the hAC lipid composition and highlights changes in lipid profiles associated with OA. Dysregulation of certain lipids, especially odd-chain fatty acids, linked to a deficiency in the enzyme HACL1, leads to pathological changes. This understanding opens potential avenues for therapies aimed at targeting lipid imbalances to slow down or treat OA.

Heart failure (HF) is a complex syndrome and a leading cause of mortality worldwide. While current medical treatment is based on known pathophysiology and is effective for many patients, the underlying cellular mechanisms are poorly understood. Energy deficiency is a characteristic of HF, marked by complex alterations in metabolism. Within the tricarboxylic acid cycle, anaplerosis emerges as an essential metabolic process responsible for replenishing lost intermediates, thereby playing a crucial role in sustaining energy metabolism and consequently cardiac function. Alterations in cardiac anaplerosis are commonly observed in HF, demonstrating potential for therapeutic intervention. This review discusses recent advances in understanding the anaplerotic adaptations that occur in HF. We also explore therapeutics that can directly modulate anaplerosis or are likely to confer cardioprotective effects through anaplerosis, which could potentially be implemented to rescue the failing heart.

There is limited evidence on the effects of different dietary sources of fats on detailed blood fatty acids (FAs). We aimed to evaluate the effects of coconut oil, olive oil and butter on circulating FA concentrations, and examine the associations between changes in plasma FAs and changes in metabolic markers. We conducted secondary analyses in the COB (coconut oil, olive oil and butter) Trial that evaluated 96 healthy adults in a 4-week parallel randomized clinical trial of three dietary interventions: 50 g/d of extra-virgin coconut oil (n = 30), extra-virgin olive oil (n = 33), or unsalted butter (n = 33). We measured plasma phospholipid FA concentrations (mol% of total) using gas chromatography. Using linear regression, we estimated the effects of the interventions on changes in FAs and the associations of changes in selected FAs with changes in metabolic markers. Coconut oil doubled lauric acid (C12:0) and myristic acid (C14:0), butter increased those to a lesser extent, and olive oil reduced those. β (95% confidence interval) for changes in C12:0 comparing coconut oil to butter and olive oil were +0.04 (0.03-0.05) and +0.05 (0.04-0.06) mol%, respectively; for C14:0, +0.24 (0.17-0.32) and +0.37 (0.29-0.45), respectively. Olive oil increased oleic acid (OA) approximately by 1 mol%, while coconut oil and butter had little effect on OA. Butter increased odd-chain SFAs and trans-FAs while olive oil and coconut oil decreased them. Changes in FAs mostly showed no significant associations with changes in metabolic markers. The interventions of equal amounts of different food FA sources altered circulating FA concentrations differently.

Pentadecanoic acid (C15:0, PDA) is an odd and minor fatty acid that has been neglected in the literature until the last decade. Indeed, as a specific fatty acid of dairy fat, PDA was only used as a biomarker of dairy fat consumption. Lately, PDA was first correlated negatively with the incidence of metabolic syndrome disorder, then its physiological effects have been investigated as a protective fatty acid. PDA supplementation has been demonstrated as negatively correlated with elevated levels of leptin, plasminogen activator inhibitor-1 and insulin, and has been shown to exhibit sensitizing insulin effects with activation of AMPK pathway. PDA also reduced the severity of metabolic dysfunction-associated steatohepatitis (MASH), notably through reduced alanine transaminase and pro-inflammatory cytokines levels. The final effect described for PDA is its ability to display anti-inflammatory properties in several pathology models. Hence, considering these multiple effects, the presence of PDA could be associated with a healthier physiological state, this raises the question of whether the presence of PDA in the body, in adequate quantities, is needed to participate to health maintenance. PDA is not synthesized in sufficient quantities endogenously, so it must be provided by the diet, mainly through dairy fat, although other types of food can also contribute to the dietary intake of PDA. Essential fatty acids are described as not being endogenously synthesized in sufficient and required quantities to maintain physiological health. Thus, PDA might gather both conditions to be described as essential, yet further investigations on both criteria are needed to enhance knowledge on this odd chain fatty acid with promising impact as potential protective supplement nutrient.

Background/Objectives: Growing evidence suggests that erythrocyte membrane lipids are subject to changes during their lifespan. Factors such as the type of dietary intake and its composition contribute to the changes in red blood cell (RBC) membranes. Due to the high antioxidant content of beer, we aimed to investigate the effect of moderate beer consumption on the lipid composition of RBCs membranes from healthy overweight individuals. Methods: We conducted a four-weeks, prospective two-arm longitudinal crossed-over study, where participants (n = 36) were randomly assigned to alcohol-free beer group or traditional beer group. The lipids of RBCs membranes were assessed at the beginning and the end of the intervention by thin-layer chromatography. Results: Four-weeks of alcohol-free beer promoted changes in fatty acids (FA), free cholesterol (FC), phosphatidylethanolamine (PE) and phosphatidylcholine (PC) (p < 0.05). Meanwhile, traditional beer intake led to changes in FA, FC, phospholipids (PL), PE and PC (p < 0.05). The observed alterations in membrane lipids were found to be independent of sex and BMI as influencing factors. Conclusions: The lipid composition of erythrocyte membranes is distinctly but mildly influenced by the consumption of both non-alcoholic and conventional beer, with no effects on RBC membrane fluidity.

Prior research has highlighted inverse associations between concentrations of circulating very long-chain saturated fatty acids (VLCSFAs) and coronary artery disease (CAD). However, the intricate links involving VLCSFAs, gut microbiota, and bile acids remain underexplored.

This study examined the association of erythrocyte VLCSFAs with CHD incidence, focusing on the mediating role of gut microbiota and fecal bile acids.

This 10-y prospective study included 2383 participants without CHD at baseline. Erythrocyte VLCSFAs [arachidic acid (C20:0), behenic acid (C22:0), and lignoceric acid (C24:0)] were measured using gas chromatography at baseline, and 274 CHD incidents were documented in triennial follow-ups. Gut microbiota in 1744 participants and fecal bile acid metabolites in 945 participants were analyzed using 16S ribosomal ribonucleic acid sequencing and ultra-performance liquid chromatography-tandem mass spectrometry at middle-term.

The multivariable-adjusted hazard ratios (95% confidence interval) for CHD incidence in highest compared with lowest quartiles were 0.87 (0.61, 1.25) for C20:0, 0.63 (0.42, 0.96) for C22:0, 0.59 (0.41, 0.85) for C24:0, and 0.57 (0.39, 0.83) for total VLCSFAs. Participants with higher total VLCSFA concentrations exhibited increased abundances of Holdemanella, Coriobacteriales Incertae Sedis spp., Ruminococcaceae UCG-005 and UCG-010, and Lachnospiraceae ND3007 group. These 5 genera generated overlapping differential microbial scores (ODMSs) that accounted for 11.52% of the total VLCSFAs-CHD association (Pmediation = 0.018). Bile acids tauro_α_ and tauro_β_muricholic acid were inversely associated with ODMS and positively associated with incident CHD. Opposite associations were found for glycolithocholic acid and glycodeoxycholic acid. Mediation analyses indicated that glycolithocholic acid, glycodeoxycholic acid, and tauro_α_ and tauro_β_muricholic acid explained 56.40%, 35.19%, and 26.17% of the ODMS-CHD association, respectively (Pmediation = 0.002, 0.008, and 0.020).

Elevated erythrocyte VLCSFAs are inversely associated with CHD risk in the Chinese population, with gut microbiota and fecal bile acid profiles potentially mediating this association. The identified microbiota and bile acid metabolites may serve as potential intervention targets in future studies. This trial was registered at www.

gov as NCT03179657.

Background/Objectives. A Mediterranean diet (MD) has been associated with neuroprotective effects. We aimed to assess the MD's association with stroke prognosis and the potential mediators involved. Methods. Seventy patients with acute anterior circulation ischemic stroke were included. Dietary patterns were evaluated using the MEDAS scale, a food-frequency questionnaire, and a 24 h recall. Circulating biomarkers including insulin resistance (HOMA index), adipokines (resistin, adiponectin, leptin), choline pathway metabolites (TMAO, betaine, choline), and endothelial progenitor cells (EPCs) were measured. Early neurological improvement (ENI) at 24 h, final infarct volume, and functional outcome at 3 months were assessed. Results. Adherence to MD and olive oil consumption were associated with a lower prevalence of diabetes and atherothrombotic stroke, and with lower levels of fasting glycemia, hemoglobinA1C, insulin resistance, and TMAO levels. Monounsaturated fatty acids and oleic acid consumption correlated with lower resistin levels, while olive oil consumption was significantly associated with EPC mobilization. Multivariate analysis showed that higher MD adherence was independently associated with ENI and good functional prognosis at 3 months. EPC mobilization, lower HOMA levels, and lower resistin levels were associated with ENI, a smaller infarct volume, and good functional outcome. Conclusions. MD was associated with better prognosis after ischemic stroke, potentially mediated by lower insulin resistance, increased EPC mobilization, and lower resistin levels, among other factors.

The study's objective was to explore the chemical composition of Acanthurus sohal fish flesh and their nutritional quality. Fish samples were caught in the Red Sea, prepared, and analysed for proximate composition, fatty acid, amino acid and mineral content. The results revealed that fish flesh contained 71.1 % moisture, 20.7 % crude protein, 5 % crude lipids and 1.7 % ash. The fatty acids were dominant by 61.93 % saturated fatty acids. Palmitic was the most common (40.35 %) saturated fatty acids, while monounsaturated fatty acids and polyunsaturated fatty acids accounted for 22.59 % and 15.48 %, respectively. The fish fat consisted of appreciable amounts of odd-numbered fatty acids heptadecanoic and heptadecenoic acids standing for 1.62 % and 1.45 %, respectively. The fatty acids were predominated by C16, C18 and C20 fatty acids. The percentage of n-6/n-3 reached 2.26. Seventeen amino acids were identified in A. sohal flesh protein, eight of which were essential amino acids (EAAs); they amounted to 375.47 mg/g crude protein. Lysine was the most common EAA (64.49 mg/g crude protein). Aromatic amino acid and sulphur amino acid constituted 112.43 and 47.56 mg/g protein, respectively. The following macroelement concentration ranking was identified: Ca > P > K > Na > Mg, while the concentration of vital elements was Fe > Zn > Cu > Cr > I > Se > Co.

Long-chain n-3 polyunsaturated fatty acid (PUFA) supplementation has shown potential benefits in the prevention of coronary heart disease (CHD); however, the impact of omega-3 fatty acid levels on CHD risk remains a subject of debate. Here, we aimed to investigate the association between n-3 PUFA levels and the risk of CHD, with particular reference to the subtypes of n-3 PUFA.

Prospective studies and retrospective case-control studies analyzing n-3 PUFA levels in CHD, published up to 30 July 2022, were selected. A random effects meta-analysis was used for pooled assessment, with relative risks (RRs) expressed as 95% confidence intervals (CIs) and standardized mean differences expressed as weight mean differences (WMDs). Subgroup and meta-regression analyses were conducted to assess the impact of n-3 PUFA exposure interval on the CHD subtype variables of the study.

We included 20 prospective studies (cohort and nested case-control) and 16 retrospective case-control studies, in which n-3 PUFAs were measured. Higher levels of n-3 PUFAs (ALA, EPA, DPA, DHA, EPA + DHA, total n-3 PUFAs) were associated with a reduced risk of CHD, with RRs (95% CI) of 0.89 (0.81, 0.98), 0.83 (0.72, 0.96); 0.80 (0.67,0.95), 0.75 (0.64, 0.87), 0.83 (0.73, 0.95), and 0.80 (0.70, 0.93), respectively, p < 0.05. CHD patients had significantly lower n-3 PUFA levels compared to healthy controls (p < 0.05). In the subgroup analysis, a significant inverse trend was found for both fatal CHD and non-fatal CHD with n-3 PUFA (EPA + DHA) levels. Also, the link between n-3 PUFA levels in erythrocytes with total CHD was generally stronger than other lipid pools.

n-3 PUFAs are significantly related to CHD risk, and these findings support the beneficial effects of n-3 PUFAs on CHD.

Human milk represents the gold standard for infant nutrition, with approximately 50% of the energy in human milk derived from lipids. Odd-chain fatty acids (OCFAs) have been recognized as a category of bioactive milk fatty acids in recent research; however, limited data exist on OCFAs in human milk. This study collected human milk samples spanning the postpartum period from 0 to 400 days. Phospholipids containing OCFAs (PL-OCFAs) were determined in 486 human milk samples using hydrophilic liquid chromatography-electrospray ionization-triquadrupole-mass spectrometry. Triacylglycerols containing OCFAs (TAG-OCFAs) were analyzed in 296 human milk samples using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. The average total concentration of PL-OCFA ranged from 30.89 ± 14.27 mg L-1 to 93.48 ± 36.55 mg L-1 during lactation, and the average total TAG-OCFA content ranged from 103.1 ± 147.15 mg L-1 to 965.41 ± 651.67 mg L-1. Despite the lower absolute concentration of PL-OCFA, its relative concentration (8.75%-11.75%) was significantly higher than that of TAG-OCFA (0.37%-1.85%) throughout lactation. PC-OCFA, SM-OCFA and PE-OCFA are major sub-classes of PL-OCFA. Furthermore, C17:0 was the major chain length in both PL-OCFA and TAG-OCFA, followed by C15:0. C17:1 was characteristic of TAG-OCFA, while long-chain fatty acids C19:0, C21:0 and C23:0 were characteristic of PL-OCFA. Our findings highlighted the importance of bioactive lipids in human milk, suggesting that OCFAs could be targeted in future studies in relation to the health and development of infants.

Mounting evidence indicates a complex link between circulating saturated fatty acids (SFAs) and cardiovascular disease (CVD) risk factors, but research on erythrocyte membrane SFA associations with metabolic markers remains limited. Our study sought to investigate the correlations between erythrocyte membrane SFAs and key metabolic markers within glycemic and lipid metabolism in a Chinese population of 798 residents aged 41 to 71 from Guangzhou. Using gas chromatography-mass spectrometry, we assessed the erythrocyte membrane saturated fatty acid profile and performed multiple linear regression to evaluate the relationship between different SFA subtypes and metabolic markers. Our findings revealed that the odd-chain SFA group (C15:0 + C17:0) exhibited negative associations with fasting blood glucose (FBG), homeostatic model assessment for insulin resistance (HOMA-IR), and triglycerides (TG). Conversely, the very-long-chain SFA group (C20:0 + C22:0 + C23:0 + C24:0) exhibited positive associations with fasting insulins (FINS), HOMA-IR, total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C). Furthermore, there was no evidence supporting an association between the even-chain group (C14:0 + C16:0 + C18:0) and metabolic markers. Our findings suggest that different subtypes of SFAs have diverse effects on glycemic and lipid metabolic markers, with odd-chain SFAs associated with a lower metabolic risk. However, the results concerning the correlations between even-chain SFAs and very-long-chain SFAs with markers of glycemic and lipid metabolism pathways are confusing, highlighting the necessity for further exploration and investigation.

Our preliminary research proposed the cytochrome P450 family 7 subfamily A member 1 (CYP7A1) and hydroxyacyl-coenzyme A dehydrogenase trifunctional multienzyme complex beta subunit (HADHB) genes as candidates for association with milk-production traits in dairy cattle because of their differential expression across different lactation stages in the liver tissues of Chinese Holstein cows and their potential roles in lipid metabolism. Hence, we identified single-nucleotide polymorphisms (SNPs) of the CYP7A1 and HADHB genes and validated their genetic effects on milk-production traits in a Chinese Holstein population with the goal of providing valuable genetic markers for genomic selection (GS) in dairy cattle, This study identified five SNPs, 14:g.24676921A>G, 14:g.24676224G>A, 14:g.24675708G>T, 14:g.24665961C>T, and 14:g.24664026A>G, in the CYP7A1 gene and three SNPs, 11:g.73256269T>C, 11:g.73256227A>C, and 11:g.73242290C>T, in HADHB. The single-SNP association analysis revealed significant associations (p value ≤ 0.0461) between the eight SNPs of CYP7A1 and HADHB genes and 305-day milk, fat and protein yields. Additionally, using Haploview 4.2, we found that the five SNPs of CYP7A1 formed two haplotype blocks and that the two SNPs of HADHB formed one haplotype block; notably, all three haplotype blocks were also significantly associated with milk, fat and protein yields (p value ≤ 0.0315). Further prediction of transcription factor binding sites (TFBSs) based on Jaspar software (version 2023) showed that the 14:g.24676921A>G, 14:g.24675708G>T, 11:g.73256269T>C, and 11:g.73256227A>C SNPs could alter the 5' terminal TFBS of the CYP7A1 and HADHB genes. The 14:g.24665961C>T SNP caused changes in the structural stability of the mRNA for the CYP7A1 gene. These alterations have the potential to influence gene expression and, consequently, the phenotype associated with milk-production traits. In summary, we have confirmed the genetic effects of CYP7A1 and HADHB genes on milk-production traits in dairy cattle and identified potential functional mutations that we suggest could be used for GS of dairy cattle and in-depth mechanistic studies of animals.

Weight loss is the most effective treatment for nonalcoholic fatty liver disease (NAFLD). There is evidence that the Mediterranean diets rich in unsaturated fatty acids and fiber have beneficial effects on weight homeostasis and metabolic risk factors in individuals with NAFLD. Studies have also shown that higher circulating concentrations of pentadecanoic acid (C15:0) are associated with a lower risk for NAFLD.

To examine the effects of a Mediterranean-like, culturally contextualized Asian diet rich in fiber and unsaturated fatty acids, with or without C15:0 supplementation, in Chinese females with NAFLD.

In a double-blinded, parallel-design, randomized controlled trial, 88 Chinese females with NAFLD were randomly assigned to 1 of the 3 groups for 12 wk: diet with C15:0 supplementation (n = 31), diet without C15:0 supplementation (n = 28), or control (habitual diet and no C15:0 supplementation, n = 29). At baseline and after the intervention, body fat percentage, intrahepatic lipid content, muscle and abdominal fat, liver enzymes, cardiometabolic risk factors, and gut microbiome were assessed.

In the intention-to-treat analysis, weight reductions of 4.0 ± 0.5 kg (5.3%), 3.4 ± 0.5 kg (4.5%), and 1.5 ± 0.5 kg (2.1%) were achieved in the diet-with-C15:0, diet without-C15:0, and the control groups, respectively. The proton density fat fraction (PDFF) of the liver decreased by 33%, 30%, and 10%, respectively. Both diet groups achieved significantly greater reductions in body weight, liver PDFF, total cholesterol, gamma-glutamyl transferase, and triglyceride concentrations compared with the control group. C15:0 supplementation reduced LDL-cholesterol further, and increased the abundance of Bifidobacterium adolescentis. Fat mass, visceral adipose tissue, subcutaneous abdominal adipose tissue (deep and superficial), insulin, glycated hemoglobin, and blood pressure decreased significantly in all groups, in parallel with weight loss.

Mild weight loss induced by a Mediterranean-like diet adapted for Asians has multiple beneficial health effects in females with NAFLD. C15:0 supplementation lowers LDL-cholesterol and may cause beneficial shifts in the gut microbiome.

This trial was registered at the clinicaltrials.gov as NCT05259475.

Different types of exogenous protease supplements have a positive impact on animal performance, but their effects on the nutritional value of meat and the gut microbial community of broilers have not been extensively studied. The objective of this investigation was to determine the impact of supplementation with a novel alkaline protease derived from Bacillus licheniformis (at doses of 0, 100, 200, 300, and 400 g/t) on the fatty acid and amino acid profiles, inosine monophosphate (IMP) levels, total volatile basic nitrogen (TVB-N) content found within the breast muscle, as well as the impact on the cecal microbiota and metabolites.

Supplementation with 200-400 g/t of the novel protease resulted in a significant elevation in the concentration of essential amino acids (P < 0.001), flavor amino acids (P < 0.001), and total protein (P = 0.013) within the breast muscle. Results derived from the 16S rRNA sequencing and untargeted metabolomics analysis of the cecal content revealed that the novel protease reshaped the cecal microbial and metabolite profiles. In particular, it led to increased relative abundances of Bacteroides, Lactobacillus, Alistipes, and Eubacterium, while simultaneously causing a reduction in the metabolites of D-lactic acid and malonic acid. Moreover, correlation analyses unveiled significant relationships between distinct microbes and metabolites with the contents of IMP, fatty acids, and amino acids in the broiler's breast muscle.

In summary, the novel protease regulated the intestinal microbial community and metabolism, thereby inducing changes in the compositions of fatty acids and amino acids profiles, as well as IMP levels in broiler meat. These alterations significantly contributed to the enhancement of the nutritional value and flavor of the meat.

The effect of marine omega-3 PUFAs on risk of stroke remains unclear.

We investigated the associations between circulating and tissue omega-3 PUFA levels and incident stroke (total, ischemic, and hemorrhagic) in 29 international prospective cohorts. Each site conducted a de novo individual-level analysis using a prespecified analytical protocol with defined exposures, covariates, analytical methods, and outcomes; the harmonized data from the studies were then centrally pooled. Multivariable-adjusted HRs and 95% CIs across omega-3 PUFA quintiles were computed for each stroke outcome.

Among 183 291 study participants, there were 10 561 total strokes, 8220 ischemic strokes, and 1142 hemorrhagic strokes recorded over a median of 14.3 years follow-up. For eicosapentaenoic acid, comparing quintile 5 (Q5, highest) with quintile 1 (Q1, lowest), total stroke incidence was 17% lower (HR, 0.83 [CI, 0.76-0.91]; P<0.0001), and ischemic stroke was 18% lower (HR, 0.82 [CI, 0.74-0.91]; P<0.0001). For docosahexaenoic acid, comparing Q5 with Q1, there was a 12% lower incidence of total stroke (HR, 0.88 [CI, 0.81-0.96]; P=0.0001) and a 14% lower incidence of ischemic stroke (HR, 0.86 [CI, 0.78-0.95]; P=0.0001). Neither eicosapentaenoic acid nor docosahexaenoic acid was associated with a risk for hemorrhagic stroke. These associations were not modified by either baseline history of AF or prevalent CVD.

Higher omega-3 PUFA levels are associated with lower risks of total and ischemic stroke but have no association with hemorrhagic stroke.

We investigated changes in serum phospholipid fatty acid compositions with intake of the Japan Diet (JD) (higher consumption of fish, soybeans, vegetables, seaweed/mushrooms/konjak, and unrefined cereals with reduced consumption of animal fat, meat and poultry with fat, sweets and alcoholic drinks) recommended by the Japan Atherosclerosis Society.

A randomized parallel controlled clinical trial on JD intake was conducted on Japanese patients with dyslipidemia. Nutrition education, based on the JD or partial JD (PJD) at baseline and at 3 months, was provided and the participants were followed up for 6 months. Fatty acids comprising serum phospholipids were measured in the JD (n=44) and PJD (n=44) groups.

Fatty acid intakes of C20:4, C20:5 and C22:6 increased in the JD group as compared with the PJD group. The percentages of serum phospholipid, C22:1 and C20:5 increased, while those of C18:1, C20:3(n-6) and C20:4(n-6) decreased in the JD as compared with the PJD group at 3 months. Changes in the phospholipid concentrations of C20:5, C22:5 and C22:6 reflected those intake volumes. Serum phospholipid C20:5 and C22:6 showed inverse correlations with C18:1, C18:2, and C20:3(n-6) at baseline and the changes at 3 and 6 months. In contrast, no correlation was observed between C20:4(n-6) and those n-3 fatty acids. The ratios of fatty acid concentrations, C16:1/C16:0 and C18:1/C18:0, decreased, but the ratio of C20:4(n-6)/C20:3(n-6) increased in the JD group.

Nutrition education on the JD changed serum phospholipid fatty acid profiles in favor to prevent against cardiovascular risk factors in patients with dyslipidemia.

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.

Lifestyle modifications that include adherence to healthy dietary patterns that are low in saturated fat have been associated with reduced risk for cardiovascular disease, the leading cause of death globally. Whole-milk dairy foods, including milk, cheese, and yogurt, are leading sources of saturated fat in the diet. Dietary guidelines around the world recommend the consumption of low-fat and fat-free dairy foods to obtain overall healthy dietary patterns that help meet nutrient recommendations while keeping within recommended calorie and saturated fat limitations. A body of observational and clinical evidence indicates, however, that whole-milk dairy food consumption, despite saturated fat content, does not increase the risk for cardiovascular disease. This review describes the proposed biological mechanisms underlying inverse associations between whole-milk dairy food consumption and risk markers for cardiometabolic health, such as altered lipid digestion, absorption, and metabolism; influence on the gut microflora; and regulation of oxidative stress and inflammatory responses. The dairy food matrix, a term used to describe how the macronutrients and micronutrients and other bioactive components of dairy foods are differentially packaged and compartmentalized among fluid milk, cheese, and yogurt, may dictate how each affects cardiovascular risk. Current evidence indicates consideration of dairy foods as complex food matrices, rather than delivery systems for isolated nutrients, such as saturated fatty acids, is warranted.

Pentadecanoic acid (C15:0) is an essential odd-chain saturated fatty acid with broad activities relevant to protecting cardiometabolic, immune, and liver health. C15:0 activates AMPK and inhibits mTOR, both of which are core components of the human longevity pathway. To assess the potential for C15:0 to enhance processes associated with longevity and healthspan, we used human cell-based molecular phenotyping assays to compare C15:0 with three longevity-enhancing candidates: acarbose, metformin, and rapamycin. C15:0 (n = 36 activities in 10 of 12 cell systems) and rapamycin (n = 32 activities in 12 of 12 systems) had the most clinically relevant, dose-dependent activities. At their optimal doses, C15:0 (17 µM) and rapamycin (9 µM) shared 24 activities across 10 cell systems, including anti-inflammatory (e.g., lowered MCP-1, TNFα, IL-10, IL-17A/F), antifibrotic, and anticancer activities, which are further supported by previously published in vitro and in vivo studies. Paired with prior demonstrated abilities for C15:0 to target longevity pathways, hallmarks of aging, aging rate biomarkers, and core components of type 2 diabetes, heart disease, cancer, and nonalcoholic fatty liver disease, our results support C15:0 as an essential nutrient with activities equivalent to, or surpassing, leading longevity-enhancing candidate compounds.

Lipid signaling is involved in longevity regulation, but which specific lipid molecular species affect human biological aging remains largely unknown. We investigated the relation between complex lipids and DNA methylation-based metrics of biological aging among 4181 participants (mean age 55.1 years (range 30.0-95.0)) from the Rhineland Study, an ongoing population-based cohort study in Bonn, Germany. The absolute concentration of 14 lipid classes, covering 964 molecular species and 267 fatty acid composites, was measured by Metabolon Complex Lipid Panel. DNA methylation-based metrics of biological aging (AgeAccelPheno and AgeAccelGrim) were calculated based on published algorithms. Epigenome-wide association analyses (EWAS) of biological aging-associated lipids and pathway analysis were performed to gain biological insights into the mechanisms underlying the effects of lipidomics on biological aging. We found that higher levels of molecular species belonging to neutral lipids, phosphatidylethanolamines, phosphatidylinositols, and dihydroceramides were associated with faster biological aging, whereas higher levels of lysophosphatidylcholine, hexosylceramide, and lactosylceramide species were associated with slower biological aging. Ceramide, phosphatidylcholine, and lysophosphatidylethanolamine species with odd-numbered fatty acid tail lengths were associated with slower biological aging, whereas those with even-numbered chain lengths were associated with faster biological aging. EWAS combined with functional pathway analysis revealed several complex lipids associated with biological aging as important regulators of known longevity and aging-related pathways.

Several studies have associated dietary saturated fatty acids (SFAs) with cardiovascular risk but there are still many controversies. Most of these studies have focused on the effects of palmitic acid on circulating lipids. Stearic acid usually shows a neutral effect on blood lipids, however, there is a lack of clinical studies assessing the link with inflammatory and endothelial dysfunction markers.

To evaluate the association of red blood cell (RBC) SFA (palmitic and stearic acids) with circulating inflammatory and endothelial dysfunction biomarkers.

Cross-sectional study of 79 adults of both sexes with at least one cardiovascular risk factor but without previous events (acute myocardial infarction or stroke). Plasma biomarkers - lipids, glucometabolic markers, high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), interleukin-10 (IL-10), monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor-α (TNF-α) - and RBC palmitic and stearic fatty acids were analyzed. The associations were assessed by correlation and multiple linear regression analyses, with statistical significance set at p < 0.05.

Palmitic acid showed no significant associations with traditional cardiovascular risk factors or inflammatory markers. Stearic acid, on the other hand, was inversely correlated with blood cholesterol and triglycerides, but independently associated with hs-CRP, IL-6, and TNF-α.

Stearic acid is associated with inflammatory and endothelial dysfunction biomarkers in individuals with at least one cardiovascular risk factor.

We aimed to review the association of dietary fats and risk of coronary events in adults. We searched PubMed, Embase, CENTRAL, Scopus, and Web of Sciences to April 2022 for prospective cohorts and randomized trials investigating the association of dietary intake and biomarkers of fats and fatty acid interventions and the risk of coronary events. We performed random-effects meta-analyses to estimate relative risk (RR) for the top versus bottom tertiles of exposures. One-hundered sixty-five prospective cohorts and randomized trials were included. Dietary intake and biomarkers of total fat and saturated, monounsaturated, and polyunsaturated fatty acids were not associated with the risk of coronary events. Dietary intake of trans fatty acids, palmitic acid, stearic acid, and saturated fatty acids from meat and unprocessed meat was modestly associated with a higher risk and, in contrast, intake of alpha-linolenic acid, long-chain omega-3 fatty acids, and linoleic acid was modestly associated with a lower risk. Supplementation with long-chain omega-3 fatty acids and increasing the consumption of alpha-linolenic and linoleic acids in place of saturated fats reduced the risk of coronary events. Existing evidence, in its totality, provides a modest support in favor of current recommendations suggesting replacement of saturated fats with polyunsaturated fats.

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.

Odd chain fatty acids (OCFAs) present in very low level at nearly 1% of total fatty acids in human plasma and thus their functions were usually ignored. Recent epidemiological studies have shown that OCFAs are inversely associated with a variety of disease risks. However, the contribution of OCFAs incorporated into complex lipids remains elusive. Here, we developed a targeted odd chain fatty acyl containing lipidomics method based on equivalent carbon number and retention time prediction. The method displayed good reproducibility and robustness as shown by peak width at half height within 0.7 min and coefficient of variation (CV) under 20%. A total number of 776 lipid species with odd chain fatty acyl residues could be detected in the electrospray ionization (ESI) mode of reverse phase liquid chromatography-mass spectrometry, of which 309 lipids were further validated using multiple MRM transitiions. Using this method, we quantified odd chain fatty acyl containing lipidome in tissues from 12 colon cancer patients, revealing the remodeling of triacylglycerol (TAG). The dynamics of odd chain fatty acyl lipids were further consolidated by the association with genomic and proteomic feature of altered catabolism of branched chain amino acids and TAG endogenous synthesis in colon cancer. This lipidomics approach will be applicable for screening of dysregulated odd chain fatty acyl lipids, which enriches and improves the methods for diagnosis and prognosis evaluation of cancer using lipidomics.

The herb A. squarrosum is reputed to possess medicinal properties for humans, and has the potential to be a feed resource for livestock. We hypothesized that this herb would improve the meat quality of lambs. To test this hypothesis, 24 Tan ewe-lambs (27.7 ± 0.45 kg) were offered diets containing 0 (CON), 100 (AS₁₀₀), 200 (AS₂₀₀) and 300 (AS₃₀₀) g A. squarrosum/kg DM, and average daily gain, carcass traits, blood metabolites, meat quality and fatty acid profiles were determined. Drip loss % and cooking loss % decreased with the AS₁₀₀ and AS₂₀₀ diets (P < 0.05). Dietary A. squarrosum reduced muscle fiber area and diameter and increased density of the meat (P < 0.05), which indicated that the meat was more tender. The concentrations of C10:0 and C18:1n-9 t were 1ower and of C17:0 and C18:3n-3 were greater in the AS₂₀₀ and AS₃₀₀ treatments than CON (P < 0.05). Our results suggest that feeding lambs up to 200 g/kg DM of A. squarrosum can increase the water-holding capacity and L* value of meat without compromising growth. Further research is needed to determine the optimal level.