Dietary Stearic Acid Research Articles

The effect of increasing canola oil and soybean oil addition to beef cattle rations based on corn silage and barley grain on the in vitro ruminal gas production and rumen fermentation

AbstractThe purpose of the current experiment was to determine the effects of ruminal fermentation parameters of the additions of canola or soybean oils at different rates (4, 8 and 12%) to beef cattle total mix rations (TMR), based on corn silage and barley grain. The addition of 4% soybean oil to TMR positively affected in vitro gas production, net energy lactation (NEL), metabolic energy (ME), and organic matter digestion (OMd). The additions of 8% and 12% of soybean oil to TMR linearly decreased ME, NEL and OMd (p < 0.05). The additions of 4, 8 and 12% canola oil to the TMR linearly decreased the in vitro gas production and estimated fermentation values (ME, NEL and OMd) (p < 0.05). All doses of soybean or canola oils in TMR reduced the molarities of total short‐chain fatty acids (tSFCA), acetic (AA), butyric (BA), propionic (PA), valeric (VA), iso‐valeric (IVA) and iso‐butyric acids (IBA) for in vitro fermentation fluid (p < 0.05). There was a negative correlation between the increasing dietary stearic, oleic and linoleic acid and the end‐products of in vitro rumen fermentation. However, increasing dietary α‐linolenic acids had no adverse effect on in vitro ruminal fermentation end‐products. As a result, 4% addition of the soybean oil, which included a higher rate of α‐linolenic acid and saturated fatty acids and a lower rate of oleic, linoleic acids according to those of canola oil, to the TMR positively affected in vitro ruminal fermentation. In addition, the ≥8% addition of canola or soybean oil adversely affected the in vitro fermentation values.

Metabolomic Investigation of Brain and Liver in Rats Fed Docosahexaenoic Acid in Regio- and Enantiopure Triacylglycerols.

N-3 polyunsaturated fatty acids (n-3 PUFAs) play important roles in cognitive functions. However, there is a lack of knowledge on the metabolic impact of regio- and stereo-specific positioning of n-3 PUFAs in dietary triacylglycerols. Rats in a state of mild n-3 PUFA deficiency are fed daily with 360mg triacylglycerols containing DHA (docosahexaenoic acid) at sn (stereospecific numbering)-1, 2, or 3 positions and 18:0 at remaining positions, or an equal amount of tristearin for 5 days. Groups fed with n-3 deficient diet and normal n-3 adequate diet are included as controls. The metabolic profiles of the brain and liver are studied using NMR (nuclear magnetic resonance)-based metabolomics. Several metabolites of significance in membrane integrity and neurotransmission, and glutamate, in particular, are significantly lower in the brain of the groups fed with sn-1 and sn-3 DHA compared to the sn-2 DHA group. Further, the tristearin and DHA groups show a lower lactate level compared to the groups fed on normal or n-3 deficient diet, suggesting a prominent role of C18:0 in regulating energy metabolism. This study sheds light on the impact of stereospecific positioning of DHA in triacylglycerols and the role of dietary stearic acid on metabolism in the brain and liver.

73 Effects of Fatty Acids Sources and Lysophospholipids on Nutrient Digestibility in Lactating Cows

Abstract Fatty acids (FA) are a common supplement for lactating cows to increase energy supply, potentially improving feed efficiency and milk and milk fat yields. However, different FA can cause varying responses probably because of different FA digestibility and interactions with other nutrients (e.g., fibers). Lysophospholipids (LPL) are natural emulsifiers and LPL as a feed additive have shown increases in FA digestibility and nutrient absorption in non-ruminant animals. This study aimed to investigate the effects of FA sources with LPL supplementation on nutrient digestibility in lactating cows. Mid-lactation cows (n = 48) were allocated into 12 blocks, and cows in each block were randomly assigned to the following dietary treatments:1) a diet with a FA supplement [1.8% of dietary dry matter (DM)] mainly containing palmitic acid (PA); 2) the PA diet with LPL (0.003% of dietary DM); 3) a diet with a FA supplement (1.8% of dietary DM) mainly containing stearic acid (SA); and 4) the SA diet with LPL (0.003% of DM). The experiment was conducted for 6 weeks, and spot samples of feces and urine were collected over 3 days (every 3 hours within a 24-hour cycle) during the last week of the experiment to determine nutrient digestibility and utilization. Data were analyzed using the mixed model with FA source, LPL, and their interaction as fixed effects and block as a random effect. The digestibility of DM, organic matter, and crude protein were not affected by the FA source and no interaction between FA and LPL was observed. However, PA had greater neutral detergent fiber (NDF) digestibility (41.4 vs. 38.8%; P = 0.04) than SA with no interaction between the FA source and LPL. In addition, as expected, PA decreased (P < 0.01) the digestibility of 16-carbon FA compared with SA due to the greater C16:0 supply, and SA decreased (P < 0.01) that of 18-carbon FA compared with PA due to the greater C18:0 supply. Supplementation of LPL did not affect digestibility of DM, OM, CP, and NDF, but increased total FA digestibility (64.7 vs. 60.5%; P = 0.02) compared with no LPL. In addition, LPL increased 18-carbon FA digestibility (68.2 vs. 74.1%; P < 0.01) compared with no LPL. An interaction between LPL and FA was observed for 16-carbon digestibility because LPL increased 16-carbon digestibility with SA but not with PA. In conclusion, PA supplementation improved fiber digestibility compared with SA, which could be a factor for increased productivity (e.g., milk fat). Supplementation of LPL was effective in increasing FA digestibility and may have potential to increase dietary energy supply or provide a similar energy supply with less dietary fat content in practice. However, more studies are needed to understand different interactions of LPL with FA sources.

Abstract P425: Diets Enriched in Stearate, Palmitate, and Oleate Differentially Modulate Gut Microbiome Composition in Post-Menopausal Women

Objective: Dietary stearic acid (18:0), a major saturated fatty acid (SFA) in Western diets, does not raise plasma LDL-C concentrations relative to other shorter chain SFAs (palmitic [16:0], myristic [14:0] and lauric [12:0]), and is associated with lower CVD risk. We investigated whether the cardioprotective effects of 18:0 and its metabolic product oleic acid (18:1, a monounsaturated fatty acid) relative to 16:0 is mediated via alterations in the gut microbiome. Methods: Twenty mildly hypercholesterolemic (LDL-C>100mg/dL) post-menopausal women (50-85 years; BMI 25-35kg/m 2 ) consumed each of 3 isocaloric diets for 5 weeks according to a randomized controlled cross-over design. Diets provided 55%E carbohydrate, 15%E protein and 30%E fat with half of the fat provided by 16:0, 18:0 or 18:1, respectively. Fecal samples were collected at the end of each diet phase and shotgun metagenomic sequencing was performed. Alpha diversity (Shannon index, Simpson index and observed counts) was compared between diet groups using two-sample non-parametric tests. Beta-diversity was assessed using Bray-Curtis dissimilarity with PERMANOVA test. Differences in metagenomic features by diet group were evaluated using Partial Least Squares-Discriminant Analysis (PLS-DA) models of pairwise diet differences developed using the R package ‘mixOmics’. Results: No significant differences were observed in alpha and beta diversity between diet groups. However, the variability in microbial relative abundance was greater after participants consumed the 18:0 and 18:1 diets compared to the 16:0 diet. Specifically, mean relative abundance of Bacterioides dorei , Bacteroides vulgatus , and Ruminococcus were highest after participants consumed the 18:0 relative to the 16:0 diet and intermediate after the 18:1 diet. The relative abundance of Coprococcus , Parabacteroides distasonis , Coprobacillus and Blautia were higher after participants consumed the 18:1 relative to the 16:0 diet. These microbial species have been associated with several anti-inflammatory pathways and decreased bacterial lipopolysaccharide production. Conclusion: These data document modest but distinctive effects of dietary SFAs on gut microbiome composition and functionality, suggesting that the favorable effects of 18:0 and 18:1 relative to 16:0 on CVD risk factors could be mediated, in part, by the gut microbiome.

Dietary butyrate, lauric acid and stearic acid improve gut morphology and epithelial cell turnover in weaned piglets.

This study was to evaluate the effects of the supplementation of saturated fatty acids with different chain lengths on growth performance, intestinal morphology, epithelial cell proliferation, differentiation and apoptosis in weaned piglets. Thirty-two weaned piglets (Duroc × Landrace × Yorkshire, BW = 7.81 ± 0.26 kg) were weaned at 21 d and randomly assigned to 1 of 4 experimental treatments: (1) a basal diet (control); (2) control + 0.3% butyrate (BT); (3) control + 0.3% lauric acid (LA); (4) control + 0.3% stearic acid (SA). All piglets were then slaughtered for tissue sampling after having been fed experimental diets for 28 d after weaning. Supplementation of BT increased the gain-to-feed ratio (G:F) (P < 0.05) compared to piglets fed the control diet from 14 to 28 d. In addition, the villus height (VH) to crypt depth (CD) ratio (VH:CD ratio) of the ileum were higher in the BT and LA diets than that of the control diet (P < 0.05). The SA-supplemented diet increased ileal VH (P < 0.05), whereas the BT-supplemented diet increased jejunal CD (P < 0.05). Compared to the control, diets supplemented with BT, LA, or SA all tended to increase jejunal proliferation (Ki67/crypt positive cells) (P = 0.190); diets supplemented with BT or SA significantly increased the number of ki67-positive cells in the ileal crypt (P < 0.05). Furthermore, in the jejunum, the protein expression of activated caspase 3 and villin were increased in piglets fed BT, LA, or SA diets compared to those on the control diet (P < 0.05). In the ileum, compared with the control diet, the BT diet tended to increase the protein level of mammalian phosphorylation target of rapamycin (p-mTOR, P < 0.10); LA or SA diets significantly increased p-mTOR protein expression (P < 0.05). These results show that dietary supplementation of BT, LA, or SA promotes jejunal cell renewal in weaned piglets. At the same time, increased proliferation of ileal crypt cells by promoting p-mTOR expression has beneficial effects on ileal morphology in weaned piglets.

Transcriptome Analysis of the Marine Nematode Litoditis marina in a Chemically Defined Food Environment with Stearic Acid Supplementation

Stearic acid represents one of the most abundant fatty acids in the Western diet and profoundly regulates health and diseases of animals and human beings. We previously showed that stearic acid supplementation promoted development of the terrestrial model nematode Caenorhabditis elegans in chemically defined CeMM food environment. However, whether stearic acid regulates development of other nematodes remains unknown. Here, we found that dietary supplementation with stearic acid could promote the development of the marine nematode Litoditis marina, belonging to the same family as C. elegans, indicating the conserved roles of stearic acid in developmental regulation. We further employed transcriptome analysis to analyze genome-wide transcriptional signatures of L. marina with dietary stearic acid supplementation. We found that stearic acid might promote development of L. marina via upregulation of the expression of genes involved in aminoacyl-tRNA biosynthesis, translation initiation and elongation, ribosome biogenesis, and transmembrane transport. In addition, we observed that the expression of neuronal signaling-related genes was decreased. This study provided important insights into how a single fatty acid stearic acid regulates development of marine nematode, and further studies with CRISPR genome editing will facilitate demonstrating the molecular mechanisms underlying how a single metabolite regulates animal development and health.

Comparative analysis of circRNA expression profile and circRNA-miRNA-mRNA regulatory network between palmitic and stearic acid-induced lipotoxicity to pancreatic β cells

ABSTRACT Chronic exposure to high concentrations of circulating palmitic acid and stearic acid leads to impaired β cell function, which accelerates the development of type 2 diabetes. However, differences in the mechanisms underlying this process between these two saturated fatty acids remain largely unknown. In this study, we screened for potential circular RNAs (circRNAs) and their associated regulatory pathways in palmitic acid- and stearic acid-induced mouse β-TC6 cell dysfunction. CircRNA high-throughput sequencing, gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes analysis were performed and co-expression and competing endogenous RNAs (ceRNA) networks were constructed. We identified that four circRNAs that were differentially expressed specifically in β cells exposed to palmitic acid, whereas four circRNAs were differentially expressed specifically in β cells exposed to stearic acid. Seven circRNAs were differentially co-expressed in palmitic acid- and stearic acid-treated β cells. In pathway exploration, we identified the core protein Solute carrier family 2 member 2 (SLc2a2), which is mainly involved in insulin resistance, maturity onset diabetes of the young and type 2 diabetes. The expressions of key circRNAs in β-TC6 cells were validated by Real time quantitative PCR, with a consistent result in high-throughput sequencing. The findings aid our understanding of the mechanisms governing the difference between palmitic acid- and stearic acid-induced β cell dysfunction and provide potential therapeutic targets for developing treatments against long-term high fat diet-induced β cell injury. Abbreviations: Acvr1c: Activin A receptor, type 1C; CeRNA, Competing endogenous RNAs; circRNA, circular RNA; DEcircRNA: Differentially Expressed circular RNA; DEmiRNA: Differentially Expressed microRNA; DEmRNA: Differentially Expressed mRNA; GO: Gene Ontology; HPDHigh Palmitic acid Diet; HSD: High Stearic acid Diet; KEGG: Kyoto Encyclopedia of Genes and Genomes; miRNA: microRNA; ncRNAs: non-coding RNAs; qPCR: Real time quantitative PCRS; FAs: Saturated Fatty Acids; SLc2a2: Solute carrier family 2 member 2; T2D: Type 2 Diabetes

Dietary stearic acid and palmitic acid do not differently affect ABCA1-mediated cholesterol efflux capacity in healthy men and postmenopausal women: A randomized controlled trial

The saturated fatty acid stearic acid (C18:0) lowers HDL cholesterol compared with palmitic acid (C16:0). However, the ability of HDL particles to promote cholesterol efflux from macrophages (cholesterol efflux capacity; CEC) may better predict coronary heart disease (CHD) risk than HDL cholesterol concentrations. We examined effects of exchanging dietary palmitic acid for stearic acid on ATP-binding cassette transporter A1 (ABCA1)-mediated CEC, and other conventional and emerging cardiometabolic risk makers. In a double-blind, randomized, crossover study with two 4-week isocaloric intervention periods, 34 healthy men and postmenopausal women (61.5±5.7 years, BMI: 25.4±2.5kg/m2) followed diets rich in palmitic acids or stearic acids. Difference in intakes was 6% of daily energy. ABCA1-mediated CEC was measured from J774 macrophages to apolipoprotein (apo)B-depleted serum. Compared with the palmitic-acid diet, the stearic-acid diet lowered serum LDL cholesterol (-0.14mmol/L; p=0.010), HDL cholesterol (-0.09mmol/L; p=<0.001), and apoA1 (-0.05g/L; p<0.001). ABCA1-mediated CEC did not differ between diets (p=0.280). Cholesteryl ester transfer protein (CETP) mass was higher on stearic acid (0.11mg/L; p=0.003), but CETP activity was comparable. ApoB100 did not differ, but triacylglycerol concentrations tended to be higher on stearic acid (p=0.100). Glucose concentrations were comparable. Effects on insulin and C-peptide were sex-dependent. In women, the stearic-acid diet increased insulin concentrations (1.57 μU/mL; p=0.002), while in men, C-peptide concentrations were lower (-0.15ng/mL; p=0.037). Interleukin 6 (0.15pg/mL; p=0.039) and tumor necrosis factor alpha (0.18pg/mL; p=0.005), but not high-sensitivity C-reactive protein, were higher on stearic acid. Soluble intracellular adhesion molecule (9ng/mL; p=0.033), but not soluble vascular cell adhesion molecule and endothelial-selectin concentrations decreased after stearic-acid consumption. As expected, stearic-acid intake lowered LDL cholesterol, HDL cholesterol, and apoA1. Insulin sensitivity in women and low-grade inflammation might be unfavorably affected by stearic-acid intake. However, palmitic-acid and stearic-acid intakes did not differently affect ABCA1-mediated CEC. This trial was registered at clinicaltrials.gov as NCT02835651.

Comparison of diets enriched in stearic, oleic, and palmitic acids on inflammation, immune response, cardiometabolic risk factors, and fecal bile acid concentrations in mildly hypercholesterolemic postmenopausal women—randomized crossover trial

Direct comparisons between SFAs varying in chain length, specifically palmitic acid (16:0) and stearic acid (18:0), relative to the latter's metabolic product, oleic acid (18:1), on cardiometabolic risk factors are limited. The aim of this study was to determine the relative comparability of diets enriched in palmitic acid, stearic acid, and oleic acid on inflammation and coagulation markers, T lymphocyte proliferation/ex-vivo cytokine secretion, plasma cardiometabolic risk factors, and fecal bile acid concentrations. Hypercholesterolemic postmenopausal women (n=20, mean±SD age 64±7 y, BMI 26.4±3.4 kg/m2, LDL cholesterol≥2.8 mmol/L) were provided with each of 3 diets [55% energy (%E) carbohydrate, 15%E protein, 30%E fat, with ∼50% fat contributed by palmitic acid, stearic acid, or oleic acid in each diet; 5 wk/diet phase] using a randomized crossover design with 2-wk washouts between phases. Outcome measures were assessed at the end of each phase. Fasting LDL-cholesterol and non-HDL-cholesterol concentrations were lower after the stearic acid and oleic acid diets than the palmitic acid diet (all P<0.01). Fasting HDL-cholesterol concentrations were lower after the stearic acid diet than the palmitic acid and oleic acid diets (P<0.01). The stearic acid diet resulted in lower lithocholic acid (P=0.01) and total secondary bile acid (SBA) concentrations (P=0.04) than the oleic acid diet. All other outcome measures were similar between diets. Lithocholic acid concentrations were positively correlated with fasting LDL-cholesterol concentrations (r=0.33; P=0.011). Total SBA, lithocholic acid, and deoxycholic acid concentrations were negatively correlated with fasting HDL cholesterol (r=-0.51 to -0.44; P<0.01) concentrations and positively correlated with LDL cholesterol:HDL cholesterol (r =0.37-0.54; P<0.01) ratios. Dietary stearic acid and oleic acid had similar effects on fasting LDL-cholesterol and non-HDL-cholesterol concentrations and more favorable ones than palmitic acid. Unlike oleic acid, the hypocholesterolemic effect of stearic acid may be mediated by inhibition of intestinal hydrophobic SBA synthesis. These findings add to the data suggesting there should be a reassessment of current SFA dietary guidance and Nutrient Facts panel labeling.This trial was registered at clinicaltrials.gov as NCT02145936.

High Stearic Acid diet aggravates aGVHD by promoting Th17 cells through Akkermansia muciniphila

Abstract T-cell metabolism is a promising target for controlling aGVHD. By using GC-MS technique, we previously identified that serum stearic acid/palmitic acid ratio on day 7 was an excellent biomarker to predict aGVHD after allo-HSCT, suggesting an important role of saturated fatty acid intake in the pathogenesis of aGVHD. However, the mechanism remains unknown. By using mouse aGVHD model, here we found that high stearic acid diet (HSAD), but not palmitic acid diet, significantly aggravated aGVHD, and its promoting role was mediated by gut microbiota. 16S rRNA sequencing identified Akkermansia muciniphila (Akk) was obviously increased in HSAD recipient. Add back Akk in WT mice ameliorated aGVHD-related mortality. Furthermore, depleting CD4 T cells significantly rescued HSAD induced aGVHD mortality, whereas depleting CD8 T cells could not. In addition, HSAD recipients of RORgt−/− allografts had improved survival compared with recipients of WT allografts, indicating that Th17 cells were involved in HSAD induced aGVHD. Meanwhile, we found that Th17 cells were significantly increased in aGVHD target tissues in HSAD recipients. Functional studies showed that stearic acid could promote Akk growth in vitro, and extracts from Akk significantly promoted Th17 cells differentiation in vitro, suggesting that Akk increased the proportion of Th17 cells, thereby exacerbating aGVHD.

Abstract P287: Hypocholesterolemic Effect of Dietary Stearic Acid May Be Partly Mediated via Alterations in Fecal Bile Acid Metabolism

Introduction: Dietary fat quality has a significant impact on CVD risk. Among the saturated fatty acids (FA), we and others have documented that stearic (18:0) is unique because, unlike shorter chain FA (12:0, 14:0, 16:0), it does not raise plasma LDL-C levels, relative to monounsaturated FA, such as oleic acid (18:1). The mechanism(s) responsible for this effect are not fully elucidated. Hypothesis: We tested the hypothesis that the hypocholesterolemic effect of dietary 18:0 and 18:1 relative to 16:0 is mediated by alterations in fecal bile acid metabolism. Methods: Primary (cholic, chenodeoxycholic) and secondary bile acids (SBA: lithocholic [LA], deoxycholic [DCA]) were quantified in stool samples from a randomized controlled cross-over trial examining the effect of dietary FA on CVD risk factors. Subjects (N=20 postmenopausal women, 50-85 years, BMI 25-35kg/m 2 , LDL-C &gt;100mg/dL) consumed each diet for 35 days separated by a 2 week washout period. Diets provided 55%E carbohydrate, 15%E protein and 30%E fat with half of the fat provided by 16:0, 18:0 or 18:1, respectively. CVD risk factors (lipids, glucose, insulin, inflammatory markers) were measured using standard methodology. For fecal bile acids analysis, freeze dried samples were spiked with the corresponding deuterated internal standards, followed by an overnight extraction, purification and analysis using reversed-phase liquid chromatography coupled with electrospray ionization quadrupole time of flight mass spectrometry. Quantification was by isotopic dilution. Spearman correlation coefficients were calculated between bile acids and CVD risk factors. Results: Fecal total SBA levels were significantly lower after subjects consumed the 18:0 (4.5±3.9 umol/g) compared to the 18:1 (6.8±5.7 umol/g) diet, with intermediate levels after the 16:0 diet (5.2±3.6 umol/g). This was predominantly due to significantly lower LA, and to a lesser extent DCA levels. No detectable differences were observed in primary bile acids levels. Total, LA and DCA levels were positively correlated with insulin (r=0.38 to 0.45; p&lt;0.05), hsCRP (r=0.31 to 0.37, p&lt;0.02), TG (r=0.46 to 0.60; p&lt;0.001), VLDL-C (r=0.47 to 0.63; p&lt;0.001), TC/LDL-C (r=0.42 to 0.63; p&lt;0.001) and LDL-C/HDL-C (0.37 to 0.57; p&lt;0.001) ratios, and negatively with HDL-C (r= -0.51 to -0.44; p&lt;0.001) levels. LA levels were also positively correlated with LDL-C levels (r=0.33; p=0.011). Conclusion: These data suggest that the hypocholesterolemic effect of dietary 18:0 was not mediated by increased bile acid excretion as was observed with dietary 18:1. Instead, dietary 18:0 appears to have an inhibitory effect on hydrophobic SBA synthesis in the intestine, which in turn could reduce the efficiency of cholesterol solubilization and thus cholesterol absorption. Further studies on the effects of dietary 18:0 on gut microbiome populations involved in SBA synthesis are warranted.

Dietary stearic acid regulates mitochondria in vivo in humans

Since modern foods are unnaturally enriched in single metabolites, it is important to understand which metabolites are sensed by the human body and which are not. We previously showed that the fatty acid stearic acid (C18:0) signals via a dedicated pathway to regulate mitofusin activity and thereby mitochondrial morphology and function in cell culture. Whether this pathway is poised to sense changes in dietary intake of C18:0 in humans is not known. We show here that C18:0 ingestion rapidly and robustly causes mitochondrial fusion in people within 3 h after ingestion. C18:0 intake also causes a drop in circulating long-chain acylcarnitines, suggesting increased fatty acid beta-oxidation in vivo. This work thereby identifies C18:0 as a dietary metabolite that is sensed by our bodies to control our mitochondria. This could explain part of the epidemiological differences between C16:0 and C18:0, whereby C16:0 increases cardiovascular and cancer risk whereas C18:0 decreases both.

Effects of dietary saturated fatty acid consumption on cartilage health and trauma-induced osteoarthritis in rats

Purpose: Experimental studies show that administering diets rich in lipids (high fat diets) leads to osteoarthritis (OA). Thus, it appears from the available literature that the source, or type of dietary fat and its level of saturation may be a critical factor in the development of an underlying inflammatory condition in the body that may lead to OA development. There are different types of saturated fatty acids. Western diet predominantly consist of fats rich in stearic acid, palmitic acid, myristic acid and lauric acid. However, so far no studies have investigated what type of saturated fatty acid in particular lead to cartilage damage. Therefore the goal of this present study is to evaluate the effects of administering different types of saturated diets on the morphology of the cartilage, subchondral bone and pain related behavior. Methods: The current study evaluates the chronic impact of high saturated fat feeding on joint cartilage health using a rat model. Male wistar rats weighing 330–340g received either corn starch diet or a diet rich in simple sugars including fructose together with either lauric acid (C12), myristic acid (C14), palmitic acid (C16), stearic acid (C18) or beef tallow (mainly stearic and trans fatty acids). After 16 weeks, knee OA was assessed by cartilage and synovium histology in addition to bone morphology. Serum cytokine concentrations were determined with multiplex assay. We further monitored lipid profile, glucose levels, and body weight and food consumption throughout the study period. Furthermore, the influence of different saturated fatty acid (SFA) types on the progression of OA was evaluated in menisectomy OA model by monitoring pain-related behavior, the changes in glial activity in the spinal cord (SC) and the dorsal root ganglions (DRG) of rats fed with the different saturated fat diets. Results: Our results indicate that the rats on a high-carbohydrate diet, stearic acid rich and plamitic acid diet showed cartilage degenerative changes that are similar to OA cartilage. Surprisingly, the rats that were fed with lauric acid and myristic acid saturated fats showed similar cartilage structure to control rats that were fed with corn starch diet, indicating marked differences in OA risk depending on the type of dietary fatty acids. As cartilage changes progress, we found that supplementation with stearic acid and palmitic acid markedly increased glucose intolerance, abdominal obesity, hypertension and fatty liver. However such effects were decreased in the rats that are fed with lauric and myristic acid fats. Furthermore, the rats on palmitic (PA) and stearic acid (SA) diets increased the progression of OA in menisectomy rats, which was characterized by increased knee cartilage degeneration and decreased bone volume density (BMD). In addition, these diet groups also exhibited decreased hind paw withdrawal thresholds, grip strength, and increased joint hypersensitivity compared to the other saturated fat groups. Furthermore, significant spinal astrogliosis and microgliosis were also observed in these diet groups. On the contrary, lauric acid (LA) diet group rats exhibited decreased degeneration of the cartilage, increased hind paw withdrawal thresholds, grip strength and decreased joint hypersensitivity. In addition, lower number of spinal GFAP and IBA-1 positive cells were observed signifying decreased astrogliosis and microgliosis respectively. Conclusions: In conclusion, our study indicates that effect of saturated fats on OA risk and pain depends on the kind of fatty acids present in the blood. Thus, reducing or modulating certain types of saturated fatty acids in the diet may help in preventing or slowing the progression of OA.

Stearic Acid Supplementation in High Protein to Carbohydrate (P:C) Ratio Diet Improves Physiological and Mitochondrial Functions of Drosophila melanogaster parkin Null Mutants.

Optimizing dietary macronutrients benefits the prevention and management of many human diseases but there is conflicting dietary advice for Parkinson's disease (PD), and no single strategy is universally recommended. Recently, it was shown that dietary stearic acid (C18:0) improves survival and mitochondrial functions in the parkin null Drosophila model of PD. Here, we incorporate stearic acid into high protein and high carbohydrate diets and study survival, climbing ability, mitochondrial membrane potential, respiration, basal reactive oxygen species, and conduct lipidomics assays. We observed that parkin null flies showed improvement in all assays tested when stearic acid was added to the high protein diet but not to the high carbohydrate diet. When lipid proportion was examined, we observed higher levels in flies fed the high protein diet with stearic acid diet and the high carbohydrate diet. Unexpectedly, free levels of fatty acids exhibited opposite trend. Combined, these data suggest that dietary Protein: Carbohydrate ratio and stearic acid influences levels of bound fatty acids. The mechanisms that influence free and bound fatty-acid levels remain to be explored, but one possible explanation is that breakdown products can bind to membranes and improve the mitochondrial functions of parkin null flies.

Saturated or unsaturated fat supplemented maternal diets influence omental adipose tissue proteome of suckling goat-kids

The aim of the present study was to investigate how maternal diet can influence the adipose tissue of goat kids. Omental adipose tissue proteomes of goat-kids from mothers fed with diet enriched with stearic acid (ST-kids), fish oil (FO-kids) and standard diets (CTRL) were determined by quantitative iTRAQ 2D-LC-MS/MS analysis. Twenty proteins were found to be differentially expressed in suckling kids' omental adipose tissue. Stearic acid induces changes in a higher number of proteins when compared to fish oil. Eleven proteins, namely AARS, ECl1, PMSC2, CP, HSPA8, GPD1, RPL7, OGDH, RPL24, FGA and RPL5 were decreased in ST-kids only. Four proteins, namely DLST, EEF1G, BCAP31 and RALA were decreased in FO-kids only, and one, NUCKS1, was increased. Four proteins, namely PMSC1, PPIB, TUB5×2 and EIF5A1, were be less abundant in both ST- and FO- kids. Most of the protein whose abundance was decreased in ST kids (10 out of 15) are involved in protein metabolism and catabolism pathways. Qualitative gene expression analysis confirmed that all the proteins identified by mass spectrometry, with the exception of FGA, were produced by adipose tissue. Quantitative gene expression analysis demonstrated that two proteins, namely CP, a minor acute phase protein, and ECl1, involved in fatty acid beta oxidation, were downregulated at mRNA level as well. ECl1 gene expression was downregulated in ST-kids AT as compared to Ctrl-kids and CP was downregulated in both ST- and FO-kids. The present results demonstrate that it is possible to influence adipose goat-kid proteome by modifying the maternal diet.

Stearic acid suppresses mammary gland development by inhibiting PI3K/Akt signaling pathway through GPR120 in pubertal mice

It has been demonstrated that dietary high fat diet negatively affects the pubertal mammary gland development. The aim of the present study was to investigate the effects of stearic acid (SA), an 18-carbon chain saturated fatty acid, on mammary gland development in pubertal mice and to explore the underlying mechanism. Our results demonstrated that dietary supplementation of 2% SA suppressed mammary duct development, with significant reduction of terminal end bud (TEB) number and ductal branch. In accord, the expression of proliferative marker Cyclin D1 was markedly decreased by dietary SA. Furthermore, dietary SA led to increase of G protein-coupled receptor 120 (GPR120) expression and inhibition of PI3K/Akt signaling pathway in mammary gland of pubertal mice. In good agreement with the in vivo findings, the in vitro results showed that 40 μM SA significantly suppressed proliferation of mouse mammary epithelial cell HC11 by regulating mRNA and/or protein expression of proliferative markers such as Cyclin D1/3, p21, and PCNA. Meanwhile, SA activated GPR120 and inhibited PI3K/Akt signaling pathway in a GPR120-dependent manner. In addition, SA-induced inhibition of PI3K/Akt signaling pathway, suppression of HC11 proliferation, and alteration of proliferative markers expression were abolished by knockdown of GPR120 with siRNA. Collectively, these findings showed that SA suppressed mammary gland development of pubertal mice, which was coincident with the SA-inhibited HC11 proliferation, and was associated with inhibition of PI3K/Akt signaling pathway through activation of GPR120. These data provided new insights into the regulation of mammary gland development by dietary fatty acids.

Improvement of Liver Cell Therapy in Rats by Dietary Stearic Acid.

Background:Stearic acid is known as a potent anti-inflammatory lipid. This fatty acid has profound and diverse effects on liver metabolism. The aim of this study was to investigate the effect of stearic acid on markers of hepatocyte transplantation in rats with acetaminophen (APAP)-induced liver damage.Methods:Wistar rats were randomly assigned to 10-day treatment. Stearic acid was administered to the rats with APAP-induced liver damage. The isolated liver cells were infused intraperitoneally into rats. Blood samples were obtained to evaluate the changes in the serum liver enzymes, including activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) and the level of serum albumin. To assess the engraftment of infused hepatocytes, rats were euthanized, and the liver DNA was used for PCR using sex-determining region Y (SRY) primers.Results:The levels of AST, ALT and ALP in the serum of rats with APAP-induced liver injury were significantly increased and returned to the levels in control group by day six. The APAP-induced decrease in albumin was significantly improved in rats through cell therapy, when compared with that in the APAP-alone treated rats. SRY PCR analysis showed the presence of the transplanted cells in the liver of transplanted rats.Conclusion:Stearic acid-rich diet in combination with cell therapy accelerates the recovering of hepatic dysfunction in a rat model of liver injury.

Milk production responses to dietary stearic acid vary by production level in dairy cattle

Effects of stearic acid supplementation on feed intake and metabolic and production responses of dairy cows with a wide range of milk production (32.2 to 64.4kg/d) were evaluated in a crossover design experiment with a covariate period. Thirty-two multiparous Holstein cows (142±55 d in milk) were assigned randomly within level of milk yield to treatment sequence. Treatments were diets supplemented (2% of diet dry matter) with stearic acid (SA; 98% C18:0) or control (soyhulls). The diets were based on corn silage and alfalfa and contained 24.5% forage neutral detergent fiber, 25.1% starch, and 17.3% crude protein. Treatment periods were 21 d with the final 4 d used for data and sample collection. Compared with the control, SA increased dry matter intake (DMI; 26.1 vs. 25.2kg/d) and milk yield (40.2 vs. 38.5kg/d). Stearic acid had no effect on the concentration of milk components but increased yields of fat (1.42 vs. 1.35kg/d), protein (1.19 vs. 1.14kg/d), and lactose (1.96 vs. 1.87kg/d). The SA treatment increased 3.5% fat-corrected milk (3.5% FCM; 40.5 vs. 38.6kg/d) but did not affect feed efficiency (3.5% FCM/DMI, 1.55 vs. 1.53), body weight, or body condition score compared with the control. Linear interactions between treatment and level of milk yield during the covariate period were detected for DMI and yields of milk, fat, protein, lactose, and 3.5% FCM; responses to SA were positively related to milk yield of cows. The SA treatment increased crude protein digestibility (67.4 vs. 65.5%), tended to increase neutral detergent fiber digestibility (43.6 vs. 42.3%), decreased fatty acid (FA) digestibility (56.6 vs. 76.1%), and did not affect organic matter digestibility. Fatty acid yield response, calculated as the additional FA yield secreted in milk per unit of additional FA intake, was only 13.3% for total FA and 8.2% for C18:0 plus cis-9 C18:1. Low estimated digestibility of the SA supplement was at least partly responsible for the low FA yield response. Treatment did not affect plasma insulin, glucagon, glucose, and nonesterified FA concentrations. Results show that stearic acid has the potential to increase DMI and yields of milk and milk components, without affecting conversion of feed to milk, body condition score, or body weight. Moreover, effects on DMI and yields of milk and milk components were more pronounced for higher-yielding cows than for lower-yielding cows.

Dietary stearic acid leads to a reduction of visceral adipose tissue in athymic nude mice.

Stearic acid (C18:0) is a long chain dietary saturated fatty acid that has been shown to reduce metastatic tumor burden. Based on preliminary observations and the growing evidence that visceral fat is related to metastasis and decreased survival, we hypothesized that dietary stearic acid may reduce visceral fat. Athymic nude mice, which are used in models of human breast cancer metastasis, were fed a stearic acid, linoleic acid (safflower oil), or oleic acid (corn oil) enriched diet or a low fat diet ad libitum. Total body weight did not differ significantly between dietary groups over the course of the experiment. However visceral fat was reduced by ∼70% in the stearic acid fed group compared to other diets. In contrast total body fat was only slightly reduced in the stearic acid diet fed mice when measured by dual-energy x-ray absorptiometry and quantitative magnetic resonance. Lean body mass was increased in the stearic acid fed group compared to all other groups by dual-energy x-ray absorptiometry. Dietary stearic acid significantly reduced serum glucose compared to all other diets and increased monocyte chemotactic protein-1 (MCP-1) compared to the low fat control. The low fat control diet had increased serum leptin compared to all other diets. To investigate possible mechanisms whereby stearic acid reduced visceral fat we used 3T3L1 fibroblasts/preadipocytes. Stearic acid had no direct effects on the process of differentiation or on the viability of mature adipocytes. However, unlike oleic acid and linoleic acid, stearic acid caused increased apoptosis (programmed cell death) and cytotoxicity in preadipocytes. The apoptosis was, at least in part, due to increased caspase-3 activity and was associated with decreased cellular inhibitor of apoptosis protein-2 (cIAP2) and increased Bax gene expression. In conclusion, dietary stearic acid leads to dramatically reduced visceral fat likely by causing the apoptosis of preadipocytes.

Cardiovascular disease risk of dietary stearic acid compared with trans, other saturated, and unsaturated fatty acids: a systematic review

High stearic acid (STA) soybean oil is a trans-free, oxidatively stable, non-LDL-cholesterol-raising oil that can be used to replace trans fatty acids (TFAs) in solid fat applications. The objective was to assess the cardiovascular health effects of dietary STA compared with those of trans, other saturated, and unsaturated fatty acids. We reviewed epidemiologic and clinical studies that evaluated the relation between STA and cardiovascular disease (CVD) risk factors, including plasma lipids and lipoproteins, hemostatic variables, and inflammatory markers. In comparison with other saturated fatty acids, STA lowered LDL cholesterol, was neutral with respect to HDL cholesterol, and directionally lowered the ratio of total to HDL cholesterol. STA tended to raise LDL cholesterol, lower HDL cholesterol, and increase the ratio of total to HDL cholesterol in comparison with unsaturated fatty acids. In 2 of 4 studies, high-STA diets increased lipoprotein(a) in comparison with diets high in saturated fatty acids. Three studies showed increased plasma fibrinogen when dietary STA exceeded 9% of energy (the current 90th percentile of intake is 3.5%). Replacing industrial TFAs with STA might increase STA intake from 3.0% (current) to approximately 4% of energy and from 4% to 5% of energy at the 90th percentile. One-to-one substitution of STA for TFAs showed a decrease or no effect on LDL cholesterol, an increase or no effect on HDL cholesterol, and a decrease in the ratio of total to HDL cholesterol. TFA intake should be reduced as much as possible because of its adverse effects on lipids and lipoproteins. The replacement of TFA with STA compared with other saturated fatty acids in foods that require solid fats beneficially affects LDL cholesterol, the primary target for CVD risk reduction; unsaturated fats are preferred for liquid fat applications. Research is needed to evaluate the effects of STA on emerging CVD risk markers such as fibrinogen and to understand the responses in different populations.