stearoyl-CoA Desaturase Activity Research Articles

Silibinin modulates lipid homeostasis and inhibits nuclear factor kappa B activation in experimental nonalcoholic steatohepatitis

Nonalcoholic steatohepatitis (NASH) is associated with increased liver-related mortality. Disturbances in hepatic lipid homeostasis trigger oxidative stress and inflammation (ie, lipotoxicity), leading to the progression of NASH. This study aimed at identifying whether silibinin may influence the molecular events of lipotoxicity in a mouse model of NASH. Eight-week-old db/db mice were fed a methionine-choline deficient (MCD) diet for 4 weeks and treated daily with silibinin (20 mg/kg intraperitoneally) or vehicle. Liver expression and enzyme activity of stearoyl-CoA desaturase-1 and acyl-CoA oxidase, and expression of liver fatty acid-binding protein were assessed. Hepatic levels of reactive oxygen species, thiobarbituric acid-reactive substances (TBARS), 3-nitrotyrosine (3-NT), inducible nitric oxide synthase (iNOS), and nuclear factor kappa B (NFkB) activities were also determined. Silibinin administration decreased serum alanine aminotransferase and improved liver steatosis, hepatocyte ballooning, and lobular inflammation in db/db mice fed an MCD diet. Gene expression and activity of stearoyl-CoA desaturase-1 were reduced in db/db mice fed an MCD diet compared with lean controls and were increased by silibinin; moreover, silibinin treatment induced the expression and activity of acyl-CoA oxidase and the expression of liver fatty acid-binding protein. Vehicle-treated animals displayed increased hepatic levels of reactive oxygen species and TBARS, 3-NT staining, and iNOS expression; silibinin treatment markedly decreased reactive oxygen species and TBARS and restored 3-NT and iNOS to the levels of control mice. db/db mice fed an MCD diet consistently had increased NFkB p65 and p50 binding activity; silibinin administration significantly decreased the activity of both subunits. Silibinin treatment counteracts the progression of liver injury by modulating lipid homeostasis and suppressing oxidative stress-mediated lipotoxicity and NFkB activation in experimental NASH.

Olive and Corn Oil Enriched Diets Changed the Phospholipid Fatty Acid Composition in Mice Liver after One-Thirds Hepatectomy

We examined the effect of dietary fats on the kinetics of liver regeneration after one-third partial hepatectomy (PH) in male Balb/c mice. Corn and olive supplemented diets were chosen as a model of n-6 and n-9 diets. Phospholipid fatty acids were determined by gas chromatography (GC) after previous fractionation by solid-phase extraction using aminopropyl (NH2) column, and data were analysed by nonparametric Kruskal-Wallis test. Diet enriched with corn and olive oil did not affect the balance of lipid disorders during liver regeneration after 1/3 PH. Desaturases activity direction has changed depending on the used diet. The key role in the alteration of the polar fatty acids profile at all stages of liver regeneration and examined dietary fats is played by activity of stearoyl-CoA desaturase (SCD).

Characterization of Fatty Acid Profile in the Liver of SHR/NDmcr-cp (cp/cp) Rats, a Model of the Metabolic Syndrome

The fatty acid profile of hepatic lipid in spontaneously hypertensive rats (SHR)/NDmcr-cp (cp/cp) rats (SHR/NDcp), which offer an animal model of the metabolic syndrome, was characterized by comparing those in Wistar Kyoto rats (WKY), SHR, stroke-prone spontaneously hypertensive rats (SHRSP) and SHR/NDmcr-cp (+/+) rats (SHR/ND+) . Hierarchical clustering analysis revealed that SHR/NDcp and the other four strains and/or substrains of rats were clearly disparate in fatty acid profile of hepatic lipid and that the disparity observed was due to the drastic increases in the mass of monounsaturated fatty acids, especially palmitoleic acid and oleic acid, in the liver of SHR/NDcp. Activities of stearoyl-CoA desaturase (SCD) and palmitoyl-CoA chain elongase in hepatic microsomes of SHR/NDcp were markedly higher than those of WKY, SHR, SHRSP and SHR/ND+. Activities of palmitoleoyl-CoA chain elongase in the liver of SHR/NDcp were also higher, but to a lesser extent. mRNA levels of SCD1 and elongation of very long-chain fatty acids (Elovl6), but not Elovl5, in the liver of SHR/NDcp were remarkably higher than those of the other four groups of rats. These results suggest that the enhanced expressions of SCD1 and Elovl6 induced abnormalities in fatty acid profile in the liver of SHR/NDcp.

Effect of dietary polyunsaturated fatty acids on Stearoyl CoA-Desaturase gene expression in intramuscular lipids of lamb

The effect of replacement of dietary sunflower oil (SO) with linseed oil (LO) on Stearoyl CoA desaturase (SCD) gene expression was investigated. Thirty-six lambs were randomly assigned to four groups and fed with one of the experimental diets, consisting of lucerne pellets with oil (60 g/Kg). The diets varied in the percentage of the oil supplemented and were: 100% SO; 66.6% SO plus 33.3% LO; 33.3% SO plus 66.6% LO and 100% LO. The trial period was of 7 weeks. Longissimus dorsi was removed from each carcass and stored at −80°C until the analysis. Total fatty acids composition was determined by gas-chromatograph, while SCD gene expression was assessed by Real-Time Reverse-Transcription PCR. Replacement of SO with LO decreases significantly the SCD mRNA content with a concomitant increment of polyunsatured fatty acids (PUFA) n-3. These results are related to the higher level of PUFA n-3 present in linseed than sunflower. Although, there were differences on mRNA level, there was not a simultaneously changes on SCD activity. In conclusion, PUFA n-3 act on the regulation of mRNA SCD level without affecting the activity of the relative enzyme.

Subcutaneous adipose tissue fatty acid desaturation in adults with and without rare adipose disorders

BackgroundElevated stearoyl-CoA desaturase activity has been described in obese states, with an increased desaturation index (DI) suggesting enhanced lipogenesis. Differences in the DI among various phenotypes of abnormal adiposity have not been studied. Abnormal accumulation of subcutaneous adipose tissue occurs in rare adipose disorders (RADs) including Dercum's disease (DD), multiple symmetric lipomatosis (MSL), and familial multiple lipomatosis (FML). Examining the DI in subcutaneous fat of people with DD, MSL and FML may provide information on adipose tissue fatty acid metabolism in these disorders. The aims of this pilot study were: 1) to determine if differences in adipose tissue DIs are present among RADs, and 2) to determine if the DIs correlate to clinical or biochemical parameters.MethodsSubcutaneous adipose tissue was obtained from human participants with DD (n = 6), MSL (n = 5), FML (n = 8) and obese Controls (n = 6). Fatty acid composition was determined by gas chromatography/mass spectrometry. The DIs (palmitoleic/palmitic, oleic/stearic, vaccenic/stearic ratios) were calculated from the gas chromatogram peak intensities. SCD1 gene expression was determined. Spearman's correlations between the DIs and available clinical or biochemical data were performed.ResultsIn DD subjects, the vaccenic/stearic index was lower (p < 0.05) in comparison to Controls. Percent of total of the saturated fatty acid myristic acid was higher in DD compared with Controls and FML. Percent of monounsaturated vaccenic acid in DD trended lower when compared with Controls, and was decreased in comparison to FML. In MSL, total percent of the polyunsaturated fatty acids was significantly lower than in the Control group (p < 0.05). In the total cohort of subjects, the palmitoleic/palmitic and oleic/stearic DIs positively correlated with age, BMI, and percent body fat.ConclusionsThe positive associations between the DIs and measures of adiposity (BMI and percent body fat) support increased desaturase activity in obesity. The lower vaccenic/stearic DI in DD SAT compared with Controls suggests presence of other factors involved in fat accumulation in addition to lifestyle. Other mechanisms driving fat accumulation in DD such as inflammation or lymphatic dysfunction should be investigated.

Animal factors affecting fatty acid composition of cow milk fat: A review

The review summarizes literature dealing with the effects of animal factors (breed, cow individuality, parity and stage of lactation) on fatty acid (FA) composition of milk fat. Genetic parameters affecting the composition of the FAs in milk are reviewed and the possibilities for altering milk fat composition are discussed. Cow individuality and the stage of lactation appear to be the main animal factors affecting milk fat composition. Breed and parity affect the variability in FA composition to a limited extent. Some of these factors can be used effectively to alter milk fat composition. Polymorphism of the enzymes, stearoyl-CoA desaturase (SCD) and acyl-CoA-diacylglycerol acyltransferase (DGAT) can explain to some extent the variability among cows. The great individual differences, probably given by varying SCD activities, may be used in breeding programmes, supported by the heritability estimates determined for individual FAs. Effective results can also be achieved through the combined effect of several factors. For instance, the level of conjugated linoleic acid could be increased not only by feed factors, but also through thorough knowledge of rumen biohydrogenation or by cow selection using information on SCD and DGAT polymorphism. The animal factors that are discussed are closely related to milk yield, particularly fat content. Both parameters can change FA composition. Thus, it is necessary in breeding programmes to take these relationships into consideration, along with known genetic correlations.

Enzymatic activity and genetic variation in SCD1 modulate the relationship between fatty acids and inflammation

Fatty acids (FA) represent a diverse class of molecules known to regulate inflammatory pathways. Therefore enzymes that regulate FA metabolism are attractive candidates to better understand the relationship between FA and inflammation. Stearoyl-CoA desaturase 1 (SCD1) is rate limiting for the conversion of saturated FA (SFA) to monounsaturated FA (MUFA). Evidence suggests that SCD1 activity may be positively associated with inflammation. Moreover, genetic variation in SCD1 may alter enzyme activity; however, it is unknown whether this affects inflammatory status. The goal of this study was to examine the relationships between plasma FA, SCD1 activity, and SCD1 polymorphisms with C-reactive protein (CRP) levels in young adults. SFA, MUFA, and CRP were measured in fasted plasma samples from European (n=279, 198 female and 81 male) and Asian (n=249, 179 female and 70 male) subjects, 20–29years old. Circulating levels of palmitic (16:0), palmitoleic (16:1), stearic (18:0), and oleic acids (18:1) were measured by gas chromatography and SCD1 activity was estimated by the ratio of product to precursor (16:1/16:0; 18:1/18:0). Positive associations were identified between CRP levels and 16:0 (p<2.0×10−4), 16:1 (p<0.05), and the SCD1 index (18:1/18:0; p<6.0×10−3) in European and Asian females, while 18:0 was inversely associated with CRP (p<2.0×10−4) in both groups. Ten single nucleotide polymorphisms (SNPs) in SCD1 were genotyped in all subjects. One SNP (rs2060792) was associated (p<0.05) with 16:0 and 18:0 levels in females of European descent. This same SNP was also associated with CRP levels in both groups of females (p<0.05). Overall, SCD1 activity and genetic variation have an important role in modulating the relationship between FA and inflammation in young adults.

Effects of diet and behavioral enrichment on free fatty acids in the aged canine brain

Despite several recent studies suggesting that dysregulation of brain lipid metabolism might contribute to the mechanisms of aging and Alzheimer's disease (AD), lipid metabolism has not been evaluated extensively in the aging brain. Here, we use a lipidomic approach to demonstrate that antioxidants plus mitochondrial cofactors treatment, either alone or in combination with behavioral enrichment, attenuates lipid abnormalities in the frontal cortices of aged canine in a manner correlated with cognitive scores. Our analyses revealed that the levels of free palmitoleic acid and nervonic acid were decreased in frontal cortices of aged dogs (n=5–6/group) treated with antioxidant compared with the control group. The monounsaturated/saturated fatty acid ratio, also known as “desaturation index”—an ex-vivo indicator of stearoyl-CoA desaturase activity, was also reduced in the frontal cortex of dogs treated with antioxidants compared with control groups. Increased palmitoleic acid levels and desaturation index were positively correlated with increased reversal learning errors and decreased cognitive performance. In conclusion, our study indicates that the addition of antioxidants and mitochondrial cofactors to the regular diet alters the composition of free fatty acids in the aged brain. Together with data showing increased palmitoleic acid levels in AD patients, our data suggest that reducing palmitoleic acid levels and desaturation index in the brain may be associated with improved cognitive performance.

Discovery of potent and liver-targeted stearoyl-CoA desaturase (SCD) inhibitors in a bispyrrolidine series

Inhibition of stearoyl-CoA desaturase (SCD) activity represents a potential novel mechanism for the treatment of metabolic disorders including obesity and type II diabetes. To circumvent skin and eye adverse events observed in rodents with systemically-distributed SCD inhibitors, our research efforts have been focused on the search for new and structurally diverse liver-targeted SCD inhibitors. This work has led to the discovery of novel, potent and structurally diverse liver-targeted bispyrrolidine SCD inhibitors. These compounds possess suitable cellular activity and pharmacokinetic properties to inhibit liver SCD activity in a mouse pharmacodynamic model.

Daily Intake of Cod or Salmon for 2 Weeks Decreases the 18:1n‐9/18:0 Ratio and Serum Triacylglycerols in Healthy Subjects

Intake of fish and omega-3 (n-3) fatty acids is associated with a reduced concentration of plasma triacylglycerols (TAG) but the mechanisms are not fully clarified. Stearoyl-CoA desaturase-1 (SCD1) activity, governing TAG synthesis, is affected by n-3 fatty acids. Peripheral blood mononuclear cells (PBMC) display expression of genes involved in lipid metabolism. The aim of the present study was to estimate whether intake of lean and fatty fish would influence n-3 fatty acids composition in plasma phospholipids (PL), serum TAG, 18:1n-9/18:0 ratio in plasma PL, as well as PBMC gene expression of SCD1 and fatty acid synthase (FAS). Healthy males and females (n=30), aged 20-40, consumed either 150g of cod, salmon, or potato (control) daily for 15days. During intervention docosahexaenoic acid (DHA, 22:6n-3) increased in the cod group (P<0.05), while TAG concentration decreased (P<0.05). In the salmon group both eicosapentaenoic acid (EPA, 20:5n-3) and DHA increased (P<0.05) whereas TAG concentration and the 18:1n-9/18:0 ratio decreased (P<0.05). Reduction of the 18:1n-9/18:0 ratio was associated with a corresponding lowering of TAG (P<0.05) and an increase in EPA and DHA (P<0.05). The mRNA levels of SCD1 and FAS in PBMC were not significantly altered after intake of cod or salmon when compared with the control group. In conclusion, both lean and fatty fish may lower TAG, possibly by reducing the 18:1n-9/18:0 ratio related to allosteric inhibition of SCD1 activity, rather than by influencing the synthesis of enzyme protein.

Dietary CLA Combined with Palm Oil or Ovine Fat Differentially Influences Fatty Acid Deposition in Tissues of Obese Zucker Rats

The effect of dietary conjugated linoleic acid (CLA) supplementation in combination with fat from vegetable versus animal origin on the fatty acid deposition, including that of individual 18:1 and 18:2 (conjugated and non-conjugated) isomers, in the liver and muscle of obese rats was investigated. For this purpose, 32 male Zucker rats were randomly assigned to one of four diets containing palm oil or ovine fat, supplemented or not with 1% of 1:1 cis(c)9,trans(t)11 and t10,c12 CLA isomers mixture. Total fatty acid content decreased in the liver and muscle of CLA-fed rats. In the liver, CLA increased saturated fatty acids (SFA) in 11.9% and decreased monounsaturated fatty acids (MUFA) in 6.5%. n-3 Polyunsaturated fatty acids (PUFA) relative proportions were increased in 30.6% by CLA when supplemented to the ovine fat diet. In the muscle, CLA did not affect SFA but decreased MUFA and PUFA percentages. The estimation of Δ9-indices 16 and 18 suggested that CLA inhibited the stearoyl-CoA desaturase activity in the liver (a decrease of 13-38%), in particular when supplemented to the ovine fat diet. Concerning CLA supplementation, the t10,c12 isomer percentage was 60-80% higher in the muscle than in the liver. It is of relevance that rats fed ovine fat, containing bio-formed CLA, had more c9,t11 CLA isomer deposited in both tissues than rats fed palm oil plus synthetic CLA. These results highlight the importance to further clarify the biological effects of consuming foods naturally enriched in CLA, alternatively to CLA dietary supplementation.

Omega-3 fatty acid deficiency increases stearoyl-CoA desaturase expression and activity indices in rat liver: Positive association with non-fasting plasma triglyceride levels

Although omega-3 ( n−3) fatty acids negatively regulate triglyceride biosynthesis, the mechanisms mediating this effect are poorly understood, and emerging evidence suggests that stearoyl-CoA desaturase (Scd1) is required for de novo triglyceride biosynthesis. To investigate this mechanism, we determined the effects of perinatal n−3 deficiency and postnatal repletion on rat liver Scd1 mRNA expression and activity indices (liver 16:1/16:0 and 18:1/18:0 ratios), and determined relationships with postprandial (non-fasting) plasma triglyceride levels. Rats were fed conventional diets with or without the n−3 fatty acid precursor α-linolenic acid (ALA, 18:3 n−3) during perinatal development (E0-P100), and a subset of rats fed the ALA− diet were switched to the ALA+ diet post-weaning (P21-P100, repletion). Compared with controls, rats fed the ALA− diet exhibited significantly lower liver long-chain n−3 fatty acid compositions and elevations in monounsaturated fatty acid composition, both of which were normalized in repleted rats. Liver Scd1 mRNA expression and activity indices (16:1/16:0 and 18:1/18:0 ratios) were significantly greater in n−3 deficient rats compared with controls and repleted rats. Among all rats, liver Scd1 mRNA expression was positively correlated with liver 18:1/18:0 and 16:1/16:0 ratios. Plasma triglyceride levels, but not glucose or insulin levels, were significantly greater in n−3 deficient rats compared with controls and repleted rats. Liver Scd1 mRNA expression and activity indices were positively correlated with plasma triglyceride levels. These preclinical findings demonstrate that n−3 fatty acid status is an important determinant of liver Scd1 mRNA expression and activity, and suggest that down-regulation of Scd1 is a mechanism by which n−3 fatty acids repress constitutive triglyceride biosynthesis.

Discovery of potent and liver-selective stearoyl-CoA desaturase (SCD) inhibitors in an acyclic linker series

Elevated levels of stearoyl-CoA desaturase (SCD) activity have been implicated in metabolic disorders such as obesity and type II diabetes. To circumvent skin and eye adverse events observed in rodents with systemically-distributed inhibitors, our research efforts have been focused on the search for new liver-targeting compounds. This work has led to the discovery of novel, potent and liver-selective acyclic linker SCD inhibitors. These compounds possess suitable cellular activity and pharmacokinetic properties to inhibit liver SCD activity in a mouse pharmacodynamic model.

Inhibition of stearoyl-CoA desaturase1 activates AMPK and exhibits beneficial lipid metabolic effects in vitro

Stearoyl-CoA desaturase1 (SCD1) whole body deficiency protects mice from diet-induced obesity. However the specific mechanism of how SCD1 deficiency protects mice from obesity is not clear yet. To understand the tissue-specific role of SCD1 in energy homeostasis, we investigated the responses of adipocytes, hepatocytes and myotubes to SCD1 inhibition. 3T3-L1 adipocytes treated with a SCD1 inhibitor had decreased expression of lipogenic genes including fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), and sterol-regulatory element binding protein 1c (SREBP1c) while the expression of fatty acid oxidative genes including carnitine palmitoyltransferase 1 (CPT1), uncoupling protein 2 (UCP2), and peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC1-α) remained unaltered. In mouse primary hepatocytes, treatment with the inhibitor reduced the expression of FAS, ACC, and SREBP1c but increased the expression of fatty acid oxidative genes including acyl-CoA oxidase (AOX), CPT1, and PGC1-α. In addition, inhibitor-treated C2C12 myotubes showed decrease in ACC and FAS expression and increase in expression of CPT1, AOX and PGC1-α. AMP-activated protein kinase (AMPK) is known to regulate cellular metabolism in response to available energy and AMPK activation is associated with enhancement of fatty acid oxidation and suppression of lipogenesis. In all tested cell models, AMPK phosphorylation was increased significantly when SCD1 was inhibited. Taken together, our results indicate that inhibition of SCD1 activity has beneficial lipid metabolic effects of decreased lipogenesis and/or increased fatty acid oxidation, which is at least in part due to an increase of AMPK activation.

The effect of excess cobalt on milk fatty acid profiles and transcriptional regulation of SCD, FASN, DGAT1 and DGAT2 in the mammary gland of lactating dairy cows

The main objective of this study was to investigate the effect of excess cobalt (Co) on gene expression of stearoyl-CoA desaturase (SCD), fatty acid synthase (FASN), diacylglycerol acyltransferase 1 (DGAT1) and diacylglycerol acyltransferase 2 (DGAT2) of lactating dairy cows in relation to milk fatty acid profile. Seven multiparous cows of the Norwegian Red cattle breed (NRF) had their basal diet supplemented with 1.4 g Co as a 24 g/l solution of Co-acetate per os twice daily for 7 days followed by a 9-day depuration period. Udder biopsies were performed prior to the treatment period, after 1 week of treatment and immediately after the depuration period. Excess Co reduced the proportion of all cis-9 monounsaturated fatty acids and increased the proportion of 18:0 in milk. However, gene expression levels of SCD, DGAT1, DGAT2 and FASN were not significantly altered. Our results indicate that the effect of Co on milk fatty acid profile is mediated at the post-transcriptional level by reduced activity of SCD in the mammary gland. Potential mechanisms explaining how Co might reduce stearoyl-CoA desaturation are discussed.

Stearoyl-CoA Desaturase: A Vital Checkpoint in the Development and Progression of Obesity

Stearoyl-CoA desaturase 1 (SCD-1) is the rate-limiting enzyme that catalyses the conversion of saturated to monounsaturated fatty acids. Increased SCD-1 expression and activity has been implicated in cancer, cardiovascular diseases, insulin resistance and obesity. Studies with humans, wild-type rodents, knock-out mice and cells in culture show that SCD-1 inhibition decreases lipogenesis and increases GLUT4-mediated glucose uptake in skeletal muscle. In this review, we will evaluate the role of SCD-1 as a homeostatic check-point between glucose and fatty acid metabolism in the development and progression of obesity. In addition to the role of SCD-1 in glucose and fatty acid metabolism, we will also discuss the expression and regulation of SCD-1, its specific interactions with inflammatory responses and PPARs, the role of SCD-1 derived MUFAs in obesity and the relevance of SCD desaturation index as a predictor of obesity and metabolic syndrome. Additionally, we will explore the prospects of SCD-1 as a potential drug target for the management of obesity and related disorders.

Isolation and Anti-Fatty Liver Activity of a Novel Cerebroside from the Sea CucumberAcaudina molpadioides

Cerebrosides are a kind of important bioactive substance in sea cucumber. A novel cerebroside, AMC-2, was purified from the less-polar lipid fraction of the sea cucumber Acaudina molpadioides by repeated column chromatography. The major structure of AMC-2 was analyzed by gas chromatography-mass spectra. The amide-linked fatty acid unit was confirmed to be four saturated and monounsaturated α-hydroxy fatty acids, the long-chain base was dihydroxy sphingoid base with one double bond, and the glycosyl group was glucose. We also investigated the anti-fatty liver activity of AMC-2 in rats with fatty liver induced by orotic acid. AMC-2 significantly reduced hepatic triglyceride (TG) and total cholesterol (TC) levels at a diet supplement of 0.03% and 0.006%. The indexes of stearoyl-CoA desaturase (SCD) activity and mRNA expression were significantly decreased by AMC-2. This indicates that AMC-2 ameliorated nonalcoholic fatty liver disease (NAFLD) through suppression of SCD activity and impaired the biosynthesis of monounsaturated fatty acids in the livers of the rats.

Atypical antipsychotic medications increase postprandial triglyceride and glucose levels in male rats: Relationship with stearoyl-CoA desaturase activity

Recent preclinical and clinical evidence suggests that the stearoyl-CoA desaturase-1 ( Scd1) enzyme plays a key role in the regulation of triglyceride (TG) biosynthesis and insulin sensitivity, and in vitro studies have found that antipsychotic medications up-regulate Scd1 mRNA expression. To investigate these effects in vivo, rats were treated with risperidone (1.5, 3, and 6 mg/kg/d), paliperidone (1.5, 3, and 6 mg/kg/d), olanzapine (2.5, 5, and 10 mg/kg/d), quetiapine (5, 10, and 20 mg/kg/d), haloperidol (1, and 3 mg/kg/d) or vehicle through their drinking water for 40 days. Effects on liver Scd1 mRNA expression and an index of Scd1 activity (the plasma 18:1/18:0 ratio, ‘desaturation index’) were determined, as were postprandial plasma triglyceride (TG), glucose, insulin, and polyunsaturated fatty acid (PUFA) levels. All atypical antipsychotics increased the plasma 18:1/18:0 ratio, but not liver Scd1 mRNA expression, at doses found to also increase plasma TG levels. Among all rats (n = 122), the plasma 18:1/18:0 ratio accounted for 56% of the variance in TG concentrations. The plasma 18:1/18:0 ratio was also positively associated with erythrocyte and heart membrane phospholipid 18:1 n-9 composition. All antipsychotics except risperidone increased glucose levels at specific doses, and none of the antipsychotics significantly altered insulin levels. The plasma 18:1/18:0 ratio accounted for 20% of the variance in glucose levels. Plasma omega-3 and omega-6 PUFA levels were inversely correlated with the plasma 18:1/18:0 ratio and TG and glucose levels. These in vivo data demonstrate that different atypical antipsychotic medications increase the plasma 18:1/18:0 ratio in association with elevations in postprandial TG and glucose levels, and that concomitant elevations in PUFA biosynthesis oppose these effects.

Subcutaneous and intramuscular adipose tissue stearoyl-coenzyme A desaturase gene expression and fatty acid composition in calf- and yearling-fed Angus steers1

We proposed that stearoyl-CoA desaturase (SCD) activity dictates fatty acid composition of adipose tissue and muscle in beef cattle, regardless of ruminal or hepatic fatty acid hydrogenation or desaturation. Twelve Angus steers were assigned to a calf-fed (CF) group and slaughtered at weaning (8 mo of age; n=4), 12 mo of age (n=4), or 16 mo of age (n=4). Twelve steers were assigned to a yearling-fed (YF) group and slaughtered at 12 mo of age (n=4), 16 mo of age (n=4), and 17.5 mo of age (n=4; 525 kg, market weight). Data were analyzed based on time on the corn-based finishing diet, with terminal age as a covariate, and orthogonal polynomial contrasts were tested on the main effects of treatment group and time on the finishing diet. Fatty acids from duodenal digesta, plasma, liver, LM, and subcutaneous and intramuscular adipose tissue were measured, and SCD gene expression was measured in intramuscular and subcutaneous adipose tissues. In duodenal digesta, palmitic and linoleic acids increased by 100% over the sampling period, α-linolenic acid decreased over the sampling period, and trans-vaccenic acid was greater in YF than in CF steers (all P < 0.01). The proportion of α-linolenic acid decreased over time in all tissues, including liver. The SCD index (ratio of SCD fatty acid products to SCD fatty acid substrates) increased over time in LM and in intramuscular and subcutaneous adipose tissues. The SCD:glyceraldehyde 3-phosphate dehydrogenase mRNA ratio was virtually undetectable at the initial sampling periods in subcutaneous adipose tissue of YF and CF steers, and it increased over time (P < 0.01). The SCD index and SCD:glyceraldehyde 3-phosphate dehydrogenase ratio were greater in intramuscular adipose tissue of CF steers than in that of YF steers. The SCD index did not change over time in liver and decreased over time in duodenal digesta. We conclude that, unlike essential fatty acids, the SFA and MUFA composition of adipose tissue is regulated by adipose tissue fatty acid desaturation, with little contribution from hepatic or duodenal fatty acids.

The fatty acid desaturation index of blood lipids, as a biomarker of hepatic stearoyl-CoA desaturase expression, is a predictive factor of breast cancer risk

This review summarizes epidemiological data linking the fatty acid desaturation index measured in blood lipids, as a biomarker of hepatic stearoyl-CoA desaturase activity, the key enzyme involved in the synthesis of monounsaturated fatty acids from saturated fatty acids, to breast cancer risk. The biological plausibility of this association is discussed. Epidemiological cohort studies reported an association between a high saturated to monounsaturated fatty acid ratio measured in blood lipids, indicating low stearoyl-CoA desaturase-1 activity, and decreased breast cancer risk. The suppression of stearoyl-CoA desaturase expression reduces cancer cell proliferation and in-vitro invasiveness, and dramatically impairs tumor formation and growth. These effects could not be overcome by supplying exogenous monounsaturated fatty acids. Epidemiological findings, in accordance with experimental data, suggested that decreased hepatic stearoyl-CoA desaturase expression/activity may be related to decreased risk of breast cancer.