TNF-alpha induces hepatic steatosis in mice by enhancing gene expression of sterol regulatory element binding protein-1c (SREBP-1c)

We investigated the effect of tumor necrosis factor-alpha (TNF-alpha), a member of the proinflammatory cytokine family, on steatosis of the mouse liver by analyzing morphological changes and hepatic triglyceride content in response to TNF-alpha. We also examined expression of the sterol regulatory element binding protein-1c gene. Intraperitoneal injection of TNF-alpha acutely and dramatically accelerated the accumulation of fat in the liver, as evidenced by histological analysis and hepatic triglyceride content. This treatment increased liver weight, increased serum levels of free fatty acids, and increased fatty acid synthase and sterol regulatory element binding protein-1c mRNA expression. Furthermore, intraperitoneal injection of lipopolysaccaride (LPS) to induce TNF-alpha expression also accelerated hepatic fat accumulation. Pretreatment with anti-TNF-alpha antibody attenuated the development of LPS-induced fatty change in the liver. Antibody pretreatment not only decreased sterol regulatory element binding protein-1c expression in LPS-treated mice but also attenuated the expression of suppressors of cytokine signaling-3 mRNA. This study suggests that TNF-alpha, acting downstream of LPS, increases intrahepatic fat deposition by affecting hepatic lipogenetic metabolism involving sterol regulatory element binding protein-1c.     

A novel splicing isoform of mouse sterol regulatory element-binding protein-1 (SREBP-1)

We cloned a cDNA encoding the NH2-terminal portion of mouse SREBP-1. The deduced amino acid sequence was 76% and 90% identical to human and hamster SREBP-1, respectively. We found out a novel splicing isoform of mouse SREBP-1 that lacks 42 amino acid residues composing a PEST sequence observed in unstable proteins. It has been reported that SREBP-1 is rapidly turned over in the nucleus. Although this isoform was not a dominant isoform, it might be possible that the produced protein functions differently from other isoforms including a complete PEST sequence.     

Genetic parameters for fatty acid composition and feed efficiency traits in Japanese Black cattle

We estimated the genetic parameters related to feed intake (FI), feed efficiency traits (including feed conversion ratio (FCR) and residual feed intake (RFI) of digestible crude protein (DCP) and total digestible nutrients (TDN)), beef marbling score (BMS), melting point of fat (MP) and fatty acid composition. Fat and meat (Musculus trapezius) samples were taken from the carcasses of 863 Japanese Black steers derived from 65 sires, for determination of the MP and fatty acid composition of the total lipid in intramuscular adipose tissue. Genetic parameters were estimated using uni- and bivariate animal models. In addition, pedigree information for 4841 animals was used. Heritability estimates for BMS, MP, individual fatty acids, monounsaturated fatty acids (MUFA), the ratio of saturated fatty acids to MUFA (MUS) and the ratio of elongation (ELONG) were generally high. The FI values of TDN and DCP were also high, but FCRs and RFIs of those were low (0.09 to 0.22). Genetic correlation of BMS with MP was -0.34 (favorable) and with C18:1, MUFA, MUS and ELONG values were 0.40, 0.28, 0.29 and 0.37, respectively (favorable). Genetic correlations of MP with C18:1, MUFA, MUS and ELONG were negative (also favorable) and high (-0.85, -0.98, -1.00 (-0.996) and -0.66, respectively). The correlation estimates for feed efficiency traits of DCP were quite similar to those of TDN. Genetic correlations of BMS with FCRs and RFIs of TDN and DCP were all positive (unfavorable; 0.21 to 0.51), and in particular, the correlations with RFIs of those were high. The correlations of C18:1, MUFA, MUS and ELONG with RFIs of TDN and DCP were positive (unfavorable) but low (0.06 to 0.17), whereas the corresponding correlations with FCRs of those were all negative (favorable; -0.38 to -0.10). These results suggest that the quantity and quality of beef fat can be simultaneously improved and that the quality of beef fat (fatty acid composition) can be improved directly or indirectly with MP. Furthermore, selecting MP or fatty acid traits does not significantly affect feed efficiency.     

Whole‐genome prediction of fatty acid composition in meat of Japanese Black cattle

Because fatty acid composition influences the flavor and texture of meat, controlling it is particularly important for cattle breeds such as the Japanese Black, characterized by high meat quality. We evaluated the predictive ability of single‐step genomic best linear unbiased prediction (ssGBLUP) in fatty acid composition of Japanese Black cattle by assessing the composition of seven fatty acids in 3088 cattle, of which 952 had genome‐wide marker genotypes. All sires of the genotyped animals were genotyped, but their dams were not. Cross‐validation was conducted for the 952 animals. The prediction accuracy was higher with ssGBLUP than with best linear unbiased prediction (BLUP) for all traits, and in an empirical investigation, the gain in accuracy of using ssGBLUP over BLUP increased as the deviations in phenotypic values of the animals increased. In addition, the superior accuracy of ssGBLUP tended to be more evident in animals whose maternal grandsire was genotyped than in other animals, although the effect was small.     

Whole‐genome association study for fatty acid composition of oleic acid in Japanese Black cattle

Fatty acid composition, especially oleic acid (C18:1), plays an important role in the eating quality of meat in Japanese Black cattle. Therefore, the objective of this study was to identify loci associated with C18:1 in the intramuscular fat of the trapezius muscles in Japanese Black cattle using the Illumina BovineSNP50 BeadChip whole genome single nucleotide polymorphism (SNP) assay. We also evaluated the relationship between C18:1 and three fatty acid synthesis genes, fatty acid synthase (FASN), stearoyl‐CoA desaturase and sterol regulatory element‐binding protein‐1. In this experiment, we applied a mixed model and Genomic Control approach using selective genotyping to perform a genome‐wide association study. A total of 160 animals (80 animals with higher values and 80 animals with lower values), selected from 3356 animals based on corrected phenotype, were genotyped using the Illumina BovineSNP50 BeadChip and three fatty acid synthesis genes, and the quality of these SNPs was assessed. In this study, a total of 38 955 SNPs, which included SNPs in the three fatty acid synthesis genes, were used, and the estimated inflation factor was 1.06. In the studied population, a total of 32 SNPs, including the FASN gene, had significant effects, and in particular 30 SNPs of all significant SNPs were located between 49 and 55 Mbp on chromosome 19. This study is one of the first genome‐wide association studies for fatty acid composition in a cattle population using the recently released Illumina BovineSNP50 BeadChip.     

DNA polymorphisms in bovine fatty acid synthase are associated with beef fatty acid composition

The objective of this study was to identify single nucleotide polymorphisms (SNPs) in the thioesterase (TE) domain of the bovine fatty acid synthase (FASN) gene and to evaluate the extent to which they were associated with beef fatty acid composition. The four exons in FASN that encode for the TE domain were sequenced, and three SNPs, AF285607:g.17924A>G, g.18663T>C and g.18727C>T, were identified. Purebred Angus bulls (n = 331) were classified into three genotype groups, g.17924AA (n = 121), g.17924AG (n = 168) and g.17924GG (n = 42). The g.17924A>G genotype was significantly associated with fatty acid composition of longissimus dorsi muscle of Angus bulls. Cattle with the g.17924GG genotype had lower myristic acid (C14:0; P < 0.0001), palmitic acid (C16:0, P < 0.05) and total saturated fatty acid contents (P < 0.01), greater health index (P < 0.001), oleic acid content (C18:1; P < 0.001) and total monounsaturated fatty acid concentration (P < 0.01) in the total lipids and triacylglycerols fraction than did those with the g.17924AA genotype. Because of the linkage disequilibrium between SNPs g.17924A>G and g.18663T>C, similar significant associations of fatty acid contents with the g.18663T>C genotypes were observed. In conclusion, the SNPs g.17924A>G and g.18663T>C may be used as DNA markers to select breeding stock that have a healthier fatty acid composition.