stearoyl-CoA Desaturase Gene Expression Research Articles

Abstract B039: Adipocyte regulation of ER stress and mTOR signaling in bone-metastatic PCa: The role of stearoyl-CoA desaturase

Abstract Bone metastatic disease is correlated with increased morbidity and mortality in prostate cancer (PCa) patients. Current treatments for bone-metastatic PCa are palliative, and new targets for therapy are desperately needed for this presently incurable disease. Various studies have determined that the supportive nature of the bone marrow (BM) niche and crosstalk between the bone-resident cells and the tumor lead to increased tumor cell survival and escape from therapy. Specifically, studies from our lab highlighted the critical role of bone marrow adipose tissue and its expansion due to obesity or age in PCa progression and chemoresistance in bone. Bone marrow adipocytes are metabolically active cells that, through secretion of lipids and adipokines, have the potential to affect the neighboring cells, including the tumor cells that have disseminated into the BM niche. We have shown previously that interaction with marrow adipocytes promotes lipid uptake by PCa cells, modulates their metabolic phenotype, and activates pro-survival signaling and ER/oxidative stress pathways; however, the molecular mechanisms behind the tumor-promoting effects of adipocytes are not understood. The main objective of this study was to investigate the molecular mechanisms underlying lipid-induced stress during tumor cell-adipocyte crosstalk and its functional relationship to tumor growth and progression in bone. Our preliminary data showed that adipocyte-tumor cell crosstalk increases lipid peroxidation in PCa cells, which coincides with augmented expression of ER stress markers and activation of mTOR signaling. We also observed that PCa cells under adipocyte exposure had augmented gene expression of stearoyl-CoA desaturase (SCD), an ER-resident enzyme responsible for the conversion of saturated fatty acids (SFA) to monounsaturated fatty acids (MUFA). We, therefore, hypothesized that SCD is a metabolic regulator that protects metastatic PCa cells against lipid-induced toxicity and ER stress and promotes tumor survival via activation of mTOR signaling. Here, we show that the inhibition of mTORC1 by Everolimus (EVO) decreases the gene expression of ER stress markers in PCa cells exposed to adipocytes. We also demonstrate that adipocyte-mediated induction of ER stress coincides with an increase in active mTOR signaling in PCa cells, indicating possible bidirectional crosstalk between ER stress and mTOR pathways. Notably, inhibition of SCD in PCa cells grown in Transwell co-culture with adipocytes by either siRNA or the small molecule inhibitor CAY10566 leads to reduced mTOR signaling and an increase in lipid peroxidation in PCa cells. SCD inhibition also increases the gene and protein expression of ER stress markers, specifically XBP1 (S) and ATF4, suggesting apoptosis induction. Collectively, our results place SCD as a mediator of ER stress-mTOR crosstalk and a promoter of tumor survival and suggest that targeting SCD activity might be a viable approach to rewire tumor metabolism, and inhibit metastatic progression in bone and sensitize PCa tumors to therapy. Citation Format: Alexis Wilson, Mackenzie Herroon, Shane Mecca, Laimar Garmo, Izabela Podgorski. Adipocyte regulation of ER stress and mTOR signaling in bone-metastatic PCa: The role of stearoyl-CoA desaturase [abstract]. In: Proceedings of the AACR Special Conference: Cancer Metastasis; 2022 Nov 14-17; Portland, OR. Philadelphia (PA): AACR; Cancer Res 2022;83(2 Suppl_2):Abstract nr B039.

Interplay Between Fatty Acids, Stearoyl-Co-A Desaturase, Mechanistic Target of Rapamycin, and Yes-Associated Protein/Transcriptional Coactivator With PDZ-Binding Motif in Promoting Hepatocellular Carcinoma

Interplay Between Fatty Acids, Stearoyl-Co-A Desaturase, Mechanistic Target of Rapamycin, and Yes-Associated Protein/Transcriptional Coactivator With PDZ-Binding Motif in Promoting Hepatocellular Carcinoma

Stearoyl-CoA Desaturase Activity and Gene Expression in the Adipose Tissue of Buffalo Bulls Was Unaffected by Diets with Different Fat Content and Fatty Acid Profile

Research on diet effects on buffalo meat quality may be critical to assess its possible consumption benefits in human nutrition. This study investigated, in growing buffalo bulls, the effects of two diets differing in total fat content and fatty acid profile on the activity and gene expression of Stearoyl-CoA Desaturase (SCD) in the adipose tissue and on meat quality. Twenty buffalo bulls, 6 months old, were randomly assigned to the two dietary treatments until slaughtering (about 400 kg body weight). No significant difference between the groups was observed for chemical composition, fatty acid profile and CLAs content of Longissimus thoracis as well as for the SCD gene expression. Such results seem to be in contrast with similar studies performed on other ruminant species, but confirm that important differences occur between buffalo and bovine species, such as the lower content in fat of buffalo meat. Our results also confirm that specific studies should be performed on buffalo, also in terms of the metabolic pathways activated by different diets.

Effects of single‐species microalgae diet on accumulation of lipid and carotenoid and expression of lipid‐related genes in Nan'ao Golden ScallopChlamys nobilis

Nan'ao Golden Scallop, Chlamys nobilis, is an important scallop species in aquaculture and is rich in lipids and carotenoid. Previous studies have shown that microalgae diet has a significant effect on the accumulation of total lipid content (TLC) and total carotenoid content (TCC) in bivalves. However, the effects of single-species microalgae diet on accumulation of TLC and TCC at molecular level are unclear. In this study, we used C. nobilis as a bivalve animal model to assess the effects of single-species microalgae diet (Tetraselmis subcordiformis, Dicrateria zhanjiangensis and Chaetoceros mulleri) on the accumulation of lipids and carotenoids, and the expression of stearoyl-CoA desaturase (SCD) and scavenger receptor class B-like-3 (SRB-like-3) genes in C. nobilis. The results of this study indicated that high lipid microalgae diet promoted the accumulation of TCC in C. nobilis tissues. The expression of SCD and SRB-like-3 genes was highly affected by the lipid composition of diet, in which high expression of SCD and SRB-like-3 genes was correlated with low C16:1n-9 and/or C18:1n-9t and/or C16:1/C16:0 and/or C18:1/C18:0. In intestine and adductor muscle, the expression of SCD gene was positively correlated with accumulation of TCC, TLC and fatty acid content, suggesting that SCD gene may indirectly promote the accumulation of TCC (lipid soluble) by promoting lipid accumulation. For SRB-like-3 gene, the high expression of SRB-like-3 was only correlated to the high TCC in intestine, suggesting that SRB-like-3 may be a candidate gene for carotenoid absorption in C. nobilis and has nothing to do with the transport or accumulation of carotenoid. The findings of this study are of great significance for further understanding how microalgae diet affects the accumulation of TCC and TLC, and the expression of lipid-related genes in bivalves.

Inhibition of Stearoyl-CoA Desaturase by Sterculic Oil Reduces Proliferation and Induces Apoptosis in Prostate Cancer Cell Lines

Prostate cancer (PCa) is a common type of cancer affecting male population. PCa treatments have side effects and are temporarily effective, so new therapeutic options are being investigated. Due to the high demand of energy for cell proliferation, an increase in the expression and activity of lipogenic enzymes such as the stearoyl-CoA desaturase (SCD) have been observed in PCa. Sterculic acid, contained in the seed’s oil of Malvales, is a natural inhibitor of SCD. The objective of our investigation was to evaluate the effects of sterculic oil (SO) from Sterculia apetala seeds on proliferation, cell cycle and apoptosis in prostate cancer cells. SO was administered to PC3 and LNCaP cells, and to prostate normal cells; cell viability, cell cycle, apoptosis, SCD gene and protein expression and enzymatic activity were analyzed. SO administration (4 mM sterculic acid) diminished cell viability in LNCaP and PC3 cells, arrested cell cycle in G2 and promoted apoptosis. SO diminished SCD enzymatic activity with no effects on gene nor protein expression. Our results suggest that SO might offer benefits as an adjuvant in hormonal and chemotherapy prostate cancer treatments. This is the first study to analyze the effect of SO on cancer cells.

Fatty acid biosynthesis and transcriptional regulation of Stearoyl-CoA Desaturase 1 (SCD1) in buffalo milk

BackgroundBuffalo milk is considered as a highly nutritious food owing to its higher contents of fatty acids (FA) and rich nutrient profile. Higher fat contents of buffalo milk make it suitable for processing to develop various healthy and nutritious products. Moreover, buffalo milk contains more unsaturated FAs (UFA) such as oleic and linolenic acid, which are important from the human health point of view owing to their desirable physiological effects. However, inadequate information is available about the chemical composition and mechanism of FA synthesis in buffalo milk. In this study, we hypothesized that expression of SCD1 gene could alter the biosynthesis of FA in epithelial cells of mammary gland and subsequently affect the FA contents in buffalo milk. We investigated the transcriptional and biological role of Stearoyl-CoA Desaturase 1 (SCD1) in the buffalo mammary epithelial cells (BMECs) during FA and triacylglycerol (TAG) synthesis.ResultsResults revealed that unsaturated fatty acid contents were much higher in concentration in buffalo milk as compared to Holstein cow. Significant increase in the expression level of FAS, ACACA, SREBP1, PPARG, GPAT, and AGPAT genes was observed in response to altered expression of SCD1 in buffalo milk. Moreover, change in SCD1 gene in BMECs also mediated the expression of genes related to FA biosynthesis subsequently leading to alter the FA composition. Overexpression of SCD1 significantly increased the expression of genes associated with FA and TAG synthesis leading to enhance FA and unsaturated FA contents in BMECs. However, down-regulation of SCD1 exhibited opposite consequences.ConclusionOur study provides mechanistic insights on transcriptional regulation of SCD1 to alter FA and TAG synthesis through directly or indirectly mediating biosynthesis and metabolic pathways in BMECs. We provide preliminary findings regarding engineering of FA contents in buffalo milk through SCD1 signaling.

Dietary supplementation with L-arginine and combinations of different oil sources beneficially regulates body fat deposition, lipogenic gene expression, growth performance and carcass yield in broiler chickens

Context Broiler meat with excessive of fat and saturated fatty acids content has serious health implication for consumers. The accumulation of abdominal fats in broiler chickens constitutes a loss of dietary energy and also reduces carcass yield. Oil rich in unsaturated fatty acids and l-arginine are effective for reducing fat deposition and improve meat quality. Aims The aim of this study was to examine the effects of supplementation of l-arginine (l-Arg) with four combinations of palm oil (PO) and sunflower oil (SO) on growth performance, carcass yield, fat deposition, lipogenic gene expression and blood lipid profile in broiler chickens. Methods A total of 180 1-day-old chicks (Cobb 500) were randomly assigned to five dietary treatments as: T1, 6% PO (control); T2, 6% PO + 0.25% l-Arg; T3, 4% PO + 2% SO + 0.25% l-Arg; T4, 2% PO + 4% SO + 0.25% l-Arg; and T5, 6% SO + 0.25% l-Arg. Key results Birds fed l-Arg and combinations of PO and SO had higher weight gain at starter and finisher period compared with the control. The carcass yield increased, and relative abdominal fat reduced in broiler fed with combinations of l-Arg and increased level of SO in the diet. The concentration of oleic, palmitoleic and total monounsaturated fatty acids in liver tissue decreased by addition of l-Arg in broiler diet. The palmitic and total saturated fatty acid decreased, and total unsaturated fatty acid and polyunsaturated fatty acids increased in liver tissue when PO replaced progressively by SO supplemented with l-Arg in the diet. The acetyl-CoA carboxylase , stearoyl-CoA desaturase and fatty acid synthetase gene expression tended to decrease by supplementation of l-Arg with an increased level of SO compared with control. Conclusion Supplementation with l-Arg and combination of PO and SO at the ratio of 4:2 could inhibit lipogenesis and subsequent lower abdominal fat deposition and enhance growth performance and carcass yield in broiler chickens. Implications Ratio of PO and SO, 4:2 with l-Arg supplementation in the dietary of broiler chickens can contribute to a better growth performance, lesser fat deposition and greater carcass yield.

Effect of energy intake and L-carnitine on fattening performance, carcass traits, meat quality, blood metabolites, and gene expression of lamb

• LPL and FASN were increased in adipose tissues with energy intake increasing, while LIPE and SCD were decreased. • L-carnitine supplementation did not improve growth performance and mutton quality. • L-carnitine could be used as a potential feed additive to inhibit fat accumulation in sheep. A 70-day feeding experiment was conducted on Tan sheep ( Ovis ) to study the effects of energy intake (low, medium, or high) and/or L -carnitine supplementation (0 or 200 ppm) on fattening performance, carcass traits, meat quality, and expression of lipid metabolism associated genes. A 2 × 3 factorial arrangement was designed, 144 lambs (14.21 ± 0.30 kg) were randomly divided into six groups of four replicates (six lambs per replicate). At the end of feeding experiment, 24 lambs were slaughtered and sampled to analyze indexes. The results showed that live body weight (LBW), average daily gains (ADG), tail fat weight, GR values, and carcass weight increased with increasing energy intake. Increased energy intake significantly increased cooked meat percentage, shear force, and the content of crude protein (CP), ash, and crude fat (EE) in muscle. L -carnitine supplementation significantly reduced tail fat weight, GR values, and the content of CP and EE in muscle, while cooked meat percentage and water loss rate significantly increased. However, L -carnitine supplementation did not affect the LBW and ADG indexes. The effects of L -carnitine or energy intake did not significantly affect amino acid compositions of the longissimus dorsi (LD) muscle. High-energy intake resulted in higher blood urea nitrogen concentrations; in contrast, no significant effects of energy intake were observed on total cholesterol (TC), triglyceride (TG), and glucose (GLU) concentrations. In addition, L -carnitine supplementation in the high-energy group reduced GLU serum concentrations, but did not affect the concentrations of TC and TG. The investigation of gene expression showed that lipoprotein lipase and fatty acid synthase were significantly increased in the liver, tail fat, and subcutaneous fat with energy intake, while lipase E (hormone sensitive type) and stearoyl-CoA desaturase gene expression were significantly decreased. Furthermore, the effects of L -carnitine supplementation on gene expression were opposite to those of energy intake. Significant interaction was found between energy intake and L -carnitine supplementation for EE content in muscle, blood biochemical index, and amino acid compositions in the LD muscle. In conclusion, high-energy diets promote animal growth and production performance, while accelerating fat deposition. L -carnitine supplementation had slightly effect on the improvement of performance and lamb quality, while effectively counteracting the negative influence of high-energy intake, particularly inhibiting fat accumulation.

Levels of Fecal Procyanidins and Changes in Microbiota and Metabolism in Mice Fed a High-Fat Diet Supplemented with Apple Peel.

The potential for apple peels to mitigate the deleterious effects of a high-fat diet in mice was investigated here. Mice were fed a high-fat diet supplemented with apple powders from three apple varieties or a commercial apple polyphenol. Polyphenols were characterized using colorimetric assays and high-performance liquid chromatography. Mice were tested for standard metabolic parameters. There was a dose response to dietary apple peels, with the higher intake leading to reduced weight gain and adipose tissue mass relative to the lower intake, but none of the treatments were statistically different from the control. The gene expression of liver enzyme stearoyl-CoA desaturase (Scd-1) was correlated with adipose weight, and liver enzyme cytochrome P51 (Cyp51) was downregulated by the apple diets. The feces from a subset of mice were analyzed for polyphenols and for bacteria taxa by next-generation sequencing. The results revealed that the makeup of the fecal microbiota was related to the metabolism of dietary polyphenols.

Inhibition of Stearoyl-CoA Desaturase-1 Activity Suppressed SREBP Signaling in Colon Cancer Cells and Their Spheroid Growth

Unsaturated fatty acids are critical in promoting colon tumorigenesis and its stemness. Stearoyl-CoA desaturase-1 (SCD1) is a rate-limiting lipid desaturase associated with colon cancer cell proliferation and metastasis control. This study aims to evaluate the effects of SCD1 inhibition on colon cancer spheroid growth in a three-dimensional cell culture system. An analysis of clinical data showed that increased SCD1 gene expression in colon tumors was negatively correlated with the prognosis. A chemical inhibitor of SCD1, CAY10566, inhibited the growth of colon cancer cells in both monolayer and sphere cultures. In addition, oleic acid administration—a monounsaturated fatty acid generated by the action of SCD1—prevented the suppression of sphere formation by CAY10566. RNA-sequencing data from 382 colon tumor patient samples obtained from the Cancer Genome Atlas database showed that 806 genes were SCD1-associated genes in human colon cancer. Correlation analysis identified the master regulator of lipid homeostasis sterol regulatory element-binding protein 2 (SREBP2) as a prominent transcription factor, whose expression was positively correlated with SCD1 in human colon cancer. SCD1 knockdown using siRNA in colon cancer samples, suppressed SREBP2 gene expression, providing direct evidence that SREBP signaling is under the control of SCD1 in these cells. Pathway analysis in the Ingenuity Pathways Analysis platform showed that SCD1 expression positively correlated with genes involved in multiple pathways, including lipid synthesis and incorporation, cell proliferation, and tissue tumorigenesis. Further network analysis revealed a central role for Myc in the network hierarchy of the SCD1-correlated genes. These findings suggested that SCD1 inhibition would be an effective strategy for suppressing colon cancer spheroid growth, partly through downregulating SREBP-mediated lipid and cholesterol metabolism and Myc signaling.

Inhibition of stearoyl CoA desaturase-1 activity suppresses tumour progression and improves prognosis in human bladder cancer.

Urinary bladder neoplasm is one of the most common cancers worldwide. Cancer stem cells (CSCs) have been proven to be an important cause of cancer progression and poor prognosis. In the present study, we established bladder CSCs and identified the crucial differentially expressed genes (DEGs) between these cells and parental bladder cancer cells. Analyses of bioinformatics data and clinical samples from local hospitals showed that stearoyl CoA desaturase‐1 (SCD) was the key factor among the DEGs. A significant correlation between SCD gene expression and poor prognosis among patients with bladder cancer was observed in our data. Loss‐of‐function experiments further revealed that the SCD inhibitor A939572 and SCD gene interference reduced cell proliferation and invasion. The above data suggest that SCD may serve as a novel marker for the prediction of tumour progression and poor prognosis in patients with bladder cancer.

A functional variant in the stearoyl-CoA desaturase (SCD) gene promoter affects gene expression in ovine muscle

The nutritional quality of lambs may be improved with increased stearoyl-CoA desaturase (SCD) gene expression, which increases the desaturation of stearic acid to oleic acid. The aim of this study was to evaluate the effect of the rs412429481 (FJ513370: g.31C > A) SNP located at the SCD gene on the functionality of the gene in lambs reared under different production systems. The effect of the rs412429481 SNP on gene expression in Rasa Aragonesa male lambs slaughtered at 22–24 kg was studied in two experiments. In Experiment 1 (n = 44), the semitendinosus muscle of lambs grazing alfalfa (ALF) or fed concentrates indoors (IND) was analysed; in Experiment 2 (n = 48), the semitendinosus and longissimus thoracis muscles of lambs that received supplementation with dl-α-tocopheryl acetate for different finishing periods were used. In Experiment 1, the effect of the rs412429481 SNP on the expression of the SCD gene in the semitendinosus muscle depended on the feeding group (P < 0.001), as it had no effect in ALF lambs, but CA lambs had greater SCD expression than CC lambs under the IND conditions. Moreover, ALF lambs showed lower levels of SCD gene expression than IND lambs (P < 0.05). In Experiment 2, gene expression was affected by the rs412429481 SNP in both muscles. Animals carrying the C- allele showed a lower expression rate than animals carrying the A- allele. These different expression levels were not associated with changes in the DNA methylation pattern or by the binding of specific nuclear proteins. Finally, we confirmed these results by luciferase assays, demonstrating that the SCD promoter containing the A variant had a 23.9% higher activity than the promoter containing the C variant.

Reduced expression of stearoyl-CoA desaturase-1, but not free fatty acid receptor 2 or 4 in subcutaneous adipose tissue of patients with newly diagnosed type 2 diabetes mellitus

BackgroundIn subcutaneous adipose tissue (SAT), higher stearoyl-CoA desaturase-1 (SCD1) expression has been related to improved insulin sensitivity in thiazolidinedione-treated type 2 diabetes mellitus patients. In animal models, deficiency of the free fatty acid receptor (FFAR) 2 associated with higher and FFAR4-deficiency with lower insulin sensitivity. We hypothesized that increased FFAR2 expression and reductions in FFAR4 and SCD1 expression in SAT of type 2 diabetes mellitus patients associate positively with insulin resistance and impaired beta cell function.MethodsTwenty-five type 2 diabetes mellitus patients and 25 glucose-tolerant humans (CON) matched for sex, age, and BMI underwent mixed-meal tests to assess insulin sensitivity (OGIS) and beta cell function (ΔAUC(C-peptide)0–180 min/ΔAUC(glucose)0–180 min) in a cross-sectional study. Gene and protein expression of SCD1 and FFAR2/4 were quantified in SAT biopsies.ResultsInsulin sensitivity was 14% and beta cell function 71% (both p < 0.001) lower in type 2 diabetes mellitus patients. In type 2 diabetes mellitus, SCD1 mRNA was fivefold (p < 0.001) and protein expression twofold (p < 0.01) lower. While FFAR2/4 mRNA and protein expression did not differ between groups, FFAR2 protein levels correlated negatively with beta cell function only in CON (r = −0.74, p < 0.01). However, neither SCD1 nor FFAR2/4 protein expression correlated with insulin sensitivity in both groups.ConclusionsType 2 diabetes patients have lower SCD1, which does not associate with insulin resistance. Only in non-diabetic humans, FFAR2 associated with impaired beta cell function.

Lower Stearoyl-CoA Desaturase and Hormone Sensitive Lipase Gene Expression in Superficial Subcutaneous Adipose Tissue of Male, but Not Female, Patients with Type 2 Diabetes

Mitochondrial gene expression in visceral (VAT) and lipogenesis in abdominal subcutaneous adipose tissue (SAT) are lower in insulin resistance (IR). Humans with hormone sensitive lipase (HSL) gene mutations are prone to type 2 diabetes (T2D). SAT is divided into deep (DSAT) and superficial SAT (SSAT). SSAT was speculated to be protective in T2D, but gender specificity is unknown. We hypothesized lower mitochondrial efficiency as well as lower markers of lipogenesis and lipolysis in SSAT only in male T2D patients vs. glucose-tolerant humans (CON), which may characterize dysfunctional SSAT. In 20 T2D and 20 CON matched for sex, BMI and age (female/male: 6/14 per group; 32±1 vs. 31±1 kg/m2, 52±2 vs. 54±2 years), we assessed M-values by euglycemic-hyperinsulinemic clamps, liver fat content (HCL) and VAT by MRS. In biopsies of SSAT, mitochondrial oxidative capacity was measured by respirometry, lipogenesis assessed from stearoyl-CoA desaturase (SCD) mRNA, lipolysis from adipocyte triglyceride lipase (ATGL) and HSL mRNA by RTqPCR. The insulin resistant T2D had 63% and 22% higher HCL (p&amp;lt;0.01) and VAT (p&amp;lt;0.05) than CON. In SSAT, T2D featured 20%, 50%, 70%, 49% reductions in oxidative capacity, SCD, ATGL and HSL mRNA (all p&amp;lt;0.05). Gender segregated analyzes showed higher oxidative capacity only in females, whereas only ATGL was also lower in female T2D vs. CON. In T2D, VAT was 22% lower (p&amp;lt;0.01) and HSL mRNA 70% higher (both p&amp;lt;0.001) in female than in male participants. In conclusion, lower lipogenesis and lipolysis in SSAT of male T2D patients may lead to inadequate lipid storage in SSAT, thereby promoting ectopic fat storage as HCL and VAT. Disclosure K. Bódis: None. J. Lundbom: None. T. Jelenik: None. D.F. Markgraf: None. A. Strom: None. O.P. Zaharia: None. Y. Karusheva: None. V. Burkart: None. K. Müssig: None. Y. Kupriyanova: None. M. Ouni: None. J. Hwang: None. D. Ziegler: None. A. Schuermann: None. M. Roden: Speaker's Bureau; Self; Boehringer Ingelheim GmbH. Research Support; Self; Boehringer Ingelheim GmbH. Consultant; Self; Poxel SA. Research Support; Self; Danone Nutricia Early Life Nutrition, GlaxoSmithKline plc., Nutricia Advanced Medical Nutrition, Sanofi. J. Szendroedi: None.

Adipogenic/lipogenic gene expression and fatty acid composition in chuck, loin, and round muscles in response to grain feeding of Yanbian Yellow cattle.

We hypothesized that gene expression and fatty acid composition would differ among different muscle depots and over time on a grain-based finishing diet. Additionally, we hypothesized that the concentration of SFA would decrease and the concentration of MUFA would increase proportionately with increases in percent intramuscular lipid (%IML). Ten Yanbian Yellow cattle steers (approximately 8 mo of age) were fed a corn-based diet in which the proportion of corn in the ration was increased at 4-mo intervals. Muscle samples were taken by biopsy from the chuck (trapezius), loin (longissimus dorsi), and round (biceps femoris) muscles at 12, 16, 20, 24, and 28 mo of age. The %IML increased from 12 to 28 mo of age, especially between 24 and 28 mo of age, with loin > round > chuck (age × muscle interaction P < 0.001). The percentage (g/100 g total fatty acids) of oleic acid (18:1n-9), linoleic acid (18:2n-6), and α-linolenic acid (18:3n-3), and the MUFA:SFA ratio increased with age, whereas palmitic (16:0) and stearic acid (18:0) decreased with age in all muscles (age effect P < 0.001). The expression of sterol regulatory element binding protein (SREBP1), adipose tissue fatty acid- binding protein (FABP4), stearoyl-CoA desaturase (SCD), acetyl-CoA carboxylase (ACC1), and lipoprotein lipase (LPL) increased, whereas the expression of peroxisome proliferator-activated receptor gamma (PPARγ) and fatty acid synthase (FASN) decreased with age. Expression of PPARγ, FABP4, SREBP1, SCD, FASN, ACC1, and LPL was greater in the loin than in the chuck or round (age × muscle interaction P < 0.001), although the MUFA:SFA ratio was greater in the chuck than in the loin or round (muscle effect P < 0.001). In conclusion, adipogenic gene expression was greater in the loin than in the chuck or round muscles, consistent with the greater %IML of the loin. However, the greater SCD gene expression in the loin did not result in a greater amount of MUFA in the loin, relative to the chuck and round.

UCP1 deficiency increases adipose tissue monounsaturated fatty acid synthesis and trafficking to the liver

Uncoupling protein-1 (UCP1) facilitates thermogenesis in brown and beige adipocytes and can promote energy expenditure by decreasing mitochondrial respiratory efficiency. Defects in UCP1 and brown adipose tissue thermogenesis subject animals to chronic cold stress and elicit compensatory responses to generate heat. How UCP1 regulates white adipose tissue (WAT) lipid biology and tissue crosstalk is not completely understood. Here, we probed the effect of UCP1 deficiency on FA metabolism in inguinal and epididymal WAT and investigated how these metabolic perturbations influence hepatic lipid homeostasis. We report that at standard housing temperature (21°C), loss of UCP1 induces inguinal WAT de novo lipogenesis through transcriptional activation of the lipogenic gene program and elevated GLUT4. Inguinal adipocyte hyperplasia and depot expansion accompany the increase in lipid synthesis. We also found that UCP1 deficiency elevates adipose stearoyl-CoA desaturase gene expression, and increased inguinal WAT lipolysis supports the transport of adipose-derived palmitoleate (16:1n7) to the liver and hepatic triglyceride accumulation. The observed WAT and liver phenotypes were resolved by housing animals at thermoneutral housing (30°C). These data illustrate depot-specific responses to impaired BAT thermogenesis and communication between WAT and liver in UCP1-/- mice.

Expression and Association of SCD Gene Polymorphisms and Fatty Acid Compositions in Chicken Cross

Stearoyl-CoA desaturase (SCD) is an integral membrane protein of endoplasmic reticulum (ER) that catalyzes the rate limiting step in the monounsaturated fatty acids from saturated fatty acids. Selection for fatty acids traits based on molecular marker assisted selection is needed to increase a value of chicken meat. This study was designed to analyze expression and associations of SCD gene polymorphisms with fatty acid traits in F2 kampung-broiler chicken cross. A total of 62 F2 kampung-broiler chicken cross (29 males and 33 females) were used in this study. Fatty acid traits were measured at 26 weeks of age. Samples were divided into two groups based on fatty acid traits (the highest and the lowest). Primers in exon 2 region were designed from the genomic chicken sequence. The SNP g.37284A>G was detected and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was then used to genotype. The expression of SCD gene was analyzed using quantitative real time PCR (qRT-PCR). The result showed that there were three genotypes (AA, AG, and GG) found in this study. The SCD|AciI polymorphism was significantly associated with palmitoleic acid (C16:1), fatty acids total and saturated fatty acid in 26 weeks old of F2 kampung-broiler chicken cross (P<0.05). The SCD gene was expressed for polyunsaturated fatty acids in liver tissue in two groups of chickens. In conclusion, the SCD gene could be a candidate gene that affects fatty acids traits in F2 kampung-broiler chicken cross.

Validating porcine SCD haplotype effects on fatty acid desaturation and fat deposition in different genetic backgrounds

Abstract Fatty acid composition and fat desaturation+ have profound effects on meat quality. One of the major enzymes participating in fatty acid metabolism is the stearoyl-CoA desaturase (SCD), which is the key enzyme involved in the fatty acid desaturation, in particular in the synthesis of C18:1 from C18:0 and C16:1 from C16:0. Previous studies have reported a likely causal SCD haplotype (g.2108C>T, g.2228T>C, g.2281A>G) determining desaturation potential in Duroc-based populations. In the current study we have evaluated the effects of SCD polymorphisms on fatty acid desaturation and SCD gene expression in muscle and subcutaneous fat in three experimental backcrosses and validated these effects in a Chinese-European hybrid pigs. In addition, we have evaluated the joint effects of SCD polymorphisms and major mutations (LEPR c.1987C>T, RYR1c.1843C>T, MC4Rc.1426A>G) previously reported to be involved in porcine fat deposition and fatty acids metabolism, in order to clarify SCD polymorphisms’ actual effects. The obtained results from association and gene expression analyses support the SCD haplotype effects on fatty acid desaturation, and moreover on fat atherogenic and thrombogenic indexes. It also reveals potential effects on intramuscular fat content, not previously reported, likely conditional on breed fatness status. Moreover, a new polymorphism, g.2520G>A, that could impact splicing and SCD translation and which appears in complete linkage disequilibrium with the causal SCD haplotype, has been here identified. In addition, the conducted joint analyses of SCD with LEPR, RYR1 and MC4R genetic variants show complex gene relations that could hamper the discrimination of specific gene effects and the success of selection strategies.

Linoleic acid, α-linolenic acid and enterolactone affect lipid oxidation and expression of lipid metabolism and antioxidant-related genes in hepatic tissue of dairy cows.

Although beneficial effects have been attributed to PUFA supplementation in high-yielding dairy cows, diets rich in PUFA may also increase oxidative stress in tissues such as the liver. To fully exploit the health benefits of PUFA, we believe that the addition of natural antioxidants could help in preventing oxidative damage. Using an in vitro precision-cut liver slices (PCLS) tissue culture system, we investigated the effects of different linoleic acid (LA, n-6):α-linolenic acid (ALA, n-3) ratios (LA:ALA ratio of 4, LA:ALA ratio of 15 and LA:ALA ratio of 25) in the presence or absence of the antioxidant enterolactone (ENL) on (1) the mRNA abundance of genes with key roles in hepatic lipid metabolism, oxidative stress response and inflammatory processes, (2) oxidative damages to lipids and proteins and (3) superoxide dismutase activity in early-lactating dairy cows. The addition of LA and ALA to PCLS culture media increased oxidative damage to lipids as suggested by higher concentrations of thiobarbituric acid reactive substances and increased the expression of nuclear factor erythroid 2-related factor 2 target genes. The addition of ENL was effective in preventing lipid peroxidation caused by LA and ALA. Transcript abundance of sterol regulatory element-binding transcription factor 1 and its lipogenic target genes acetyl-CoA carboxylase α, fatty acid synthase (FASN) and stearoyl-CoA desaturase (SCD) was decreased with LA and ALA, whereas ENL decreased FASN and SCD gene expression. Our results show that addition of LA and ALA to PCLS culture media lowers hepatic lipogenic gene expression and increases oxidative damages to lipids. On the other hand, addition of ENL prevents oxidative damages provoked by these PUFA.

Carcass and Meat Characteristics and Gene Expression in Intramuscular Adipose Tissue of Korean Native Cattle Fed Finishing Diets Supplemented with 5% Palm Oil.

We hypothesized that supplementing finishing diets with palm oil would promote adipogenic gene expression but depress stearoyl-CoA desaturase (SCD) gene expression in intramuscular (i.m.) adipose tissues of Hanwoo steers during fattening period (from 16 to 32 mon of age). Fourteen Hanwoo steers were allotted randomly to 2 groups of 7 steers based on initial BW and fed either a basal diet (control) or the basal diet supplemented with 5% palm oil (BDSP). At slaughter, i.m. adipose tissue was harvested for analysis of adipogenic gene expression and fatty acid composition. There were no differences in BW or average daily gain between treatment groups. Supplemental palm oil had no effect on carcass quality traits (carcass weight, backfat thickness, loin muscle area, or marbling scores) or meat color values. Palm oil increased (p<0.05) expression of AMP-activated protein kinase-α and peroxisome proliferator-activated receptor-γ, but decreased (p<0.05) CAAT/enhancer binding protein-β gene expression and tended to decrease stearoyl-CoA desaturase gene expression in i.m. adipose tissue. Palm oil increased total i.m. polyunsaturated fatty acids (p<0.05) compared to the control i.m. adipose tissue, but had no effect on saturated or monounsaturated fatty acids. Although there were significant effects of supplemental palm oil on i.m. adipose tissue gene expression, the absence of negative effects on carcass and meat characteristics indicates that palm oil could be a suitable dietary supplement for the production of Hanwoo beef cattle.