Project description:Dietary supplementation with ω-3 polyunsaturated fatty acids (ω-3 PUFAs), specifically the fatty acids docosahexaenoic acid (DHA; 22:6 ω-3) and eicosapentaenoic acid (EPA; 20:5 ω-3), is known to have beneficial health effects including improvements in glucose and lipid homeostasis and modulation of inflammation. To evaluate the efficacy of two different sources of ω-3 PUFAs, we performed gene expression profiling in the liver of mice fed diets supplemented with either fish oil or krill oil. We found that ω-3 PUFA supplements derived from a phospholipid krill fraction (krill oil) downregulated the activity of pathways involved in hepatic glucose production as well as lipid and cholesterol synthesis. The data also suggested that krill oil-supplementation increases the activity of the mitochondrial respiratory chain. Surprisingly, an equimolar dose of EPA and DHA derived from fish oil modulated fewer pathways than a krill oil-supplemented diet and did not modulate key metabolic pathways regulated by krill oil, including glucose metabolism, lipid metabolism and the mitochondrial respiratory chain. Moreover, fish oil upregulated the cholesterol synthesis pathway, which was the opposite effect of krill supplementation. Neither diet elicited changes in plasma levels of lipids, glucose or insulin, probably because the mice used in this study were young and were fed a low fat diet. Further studies of krill oil supplementation using animal models of metabolic disorders and/or diets with a higher level of fat may be required to observe these effects. Twenty-one microarrays: three diets (CO, FO, KO) x seven mice per diet x one microarray per mouse
Project description:Dynamin-related protein 1 (Drp1) plays a critical role in mitochondrial fission and liver function. The interactions between mitochondria, endoplasmic reticulum (ER), and lipid droplets (LDs) are essential for lipid metabolism. In this study, liver-specific Drp1 knockout (Drp1LiKO) mice were utilized to investigate the impact of disrupted organelle interactions. Analysis revealed increased interactions between mitochondria and LDs, as well as among ER, mitochondria, and LDs in Drp1LiKO mice. As a result, impaired fatty acid metabolism was observed, leading to liver inflammation. In vitro studies using primary hepatocytes from Drp1LiKO mice further confirmed disrupted lipid metabolism and increased inflammation. These findings underscore the significance of Drp1 in maintaining organelle interactions for proper lipid metabolism and liver health. Targeting Drp1-mediated interactions may present a promising approach for the treatment of liver diseases associated with lipid metabolism dysregulation.
Project description:Dynamin-related protein 1 (Drp1) plays a critical role in mitochondrial fission and liver function. The interactions between mitochondria, endoplasmic reticulum (ER), and lipid droplets (LDs) are essential for lipid metabolism. In this study, liver-specific Drp1 knockout (Drp1LiKO) mice were utilized to investigate the impact of disrupted organelle interactions. Analysis revealed increased interactions between mitochondria and LDs, as well as among ER, mitochondria, and LDs in Drp1LiKO mice. As a result, impaired fatty acid metabolism was observed, leading to liver inflammation. In vitro studies using primary hepatocytes from Drp1LiKO mice further confirmed disrupted lipid metabolism and increased inflammation. These findings underscore the significance of Drp1 in maintaining organelle interactions for proper lipid metabolism and liver health. Tar-geting Drp1-mediated interactions may present a promising approach for the treatment of liver diseases associated with lipid metabolism dysregulation.
Project description:This trial studies how fiber and fish oil supplements affect the metabolism and activities of colon cells in healthy individuals. Diet is an important risk factor for colorectal cancer, and several dietary components important in colorectal cancer prevention are modified by gut microbial metabolism. Giving fiber and fish oil supplements may inhibit the growth of gut cells and ultimately reduce risk of colorectal cancer.
| 2325667 | ecrin-mdr-crc
Project description:Transcriptomics studies the effects of microplastics exposure on lipid metabolism in mouse liver
Project description:Domestication has produced faster-growing strains of animals for use in agriculture, but selection has been applied with little knowledge of the underlying genetic changes that arose throughout the process. Mammals and birds have been domesticated for thousands of years whereas fish have been domesticated only recently; therefore, wild progenitor strains remain for comparison. Rainbow trout (Oncorhynchus mykiss) have undergone intensive selection and domesticated strains grow more rapidly than extant wild strains. To assess physiological pathways altered by domestication, whole-genome mRNA expression was measured in brain, muscle and liver of size-matched domestic and wild trout using a 16K (cGRASP) salmonid microarray. A large number of genes differed between strains, ranging from 3% of genes in brain to 9% in muscle. Domestic fish had more down-regulated genes in the brain relative to wild fish, whereas more genes were up-regulated in domestic liver and muscle. Relative to wild fish, there was a down-regulation of cell division and an up-regulation of structural genes in the brain of domestic fish. In liver from domestic fish, there was an up-regulation of genes related to transport with a down-regulation of lipid binding. Analysis of the functional categories for muscle indicated that most pathways, including pathways related to metabolism and catabolism, were up-regulated in domestic fish. Comparison of these results to other genomic studies on transgenic, domestic and wild salmonids suggests that similar physiological pathways are altered systemically to support faster rates of growth, regardless of the underlying genetic alteration that has caused the altered growth. Microarray analyses were performed on six individual fish per group of wild type and domestic rainbow trout hybridized (one slide per individual) against a common wild-type RNA pool.
Project description:Domestication has produced faster-growing strains of animals for use in agriculture, but selection has been applied with little knowledge of the underlying genetic changes that arose throughout the process. Mammals and birds have been domesticated for thousands of years whereas fish have been domesticated only recently; therefore, wild progenitor strains remain for comparison. Rainbow trout (Oncorhynchus mykiss) have undergone intensive selection and domesticated strains grow more rapidly than extant wild strains. To assess physiological pathways altered by domestication, whole-genome mRNA expression was measured in brain, muscle and liver of size-matched domestic and wild trout using a 16K (cGRASP) salmonid microarray. A large number of genes differed between strains, ranging from 3% of genes in brain to 9% in muscle. Domestic fish had more down-regulated genes in the brain relative to wild fish, whereas more genes were up-regulated in domestic liver and muscle. Relative to wild fish, there was a down-regulation of cell division and an up-regulation of structural genes in the brain of domestic fish. In liver from domestic fish, there was an up-regulation of genes related to transport with a down-regulation of lipid binding. Analysis of the functional categories for muscle indicated that most pathways, including pathways related to metabolism and catabolism, were up-regulated in domestic fish. Comparison of these results to other genomic studies on transgenic, domestic and wild salmonids suggests that similar physiological pathways are altered systemically to support faster rates of growth, regardless of the underlying genetic alteration that has caused the altered growth. Microarray analyses were performed on nine individual fish per group of wild type and domestic rainbow trout hybridized (one slide per individual) against a common wild-type RNA pool.
Project description:Domestication has produced faster-growing strains of animals for use in agriculture, but selection has been applied with little knowledge of the underlying genetic changes that arose throughout the process. Mammals and birds have been domesticated for thousands of years whereas fish have been domesticated only recently; therefore, wild progenitor strains remain for comparison. Rainbow trout (Oncorhynchus mykiss) have undergone intensive selection and domesticated strains grow more rapidly than extant wild strains. To assess physiological pathways altered by domestication, whole-genome mRNA expression was measured in brain, muscle and liver of size-matched domestic and wild trout using a 16K (cGRASP) salmonid microarray. A large number of genes differed between strains, ranging from 3% of genes in brain to 9% in muscle. Domestic fish had more down-regulated genes in the brain relative to wild fish, whereas more genes were up-regulated in domestic liver and muscle. Relative to wild fish, there was a down-regulation of cell division and an up-regulation of structural genes in the brain of domestic fish. In liver from domestic fish, there was an up-regulation of genes related to transport with a down-regulation of lipid binding. Analysis of the functional categories for muscle indicated that most pathways, including pathways related to metabolism and catabolism, were up-regulated in domestic fish. Comparison of these results to other genomic studies on transgenic, domestic and wild salmonids suggests that similar physiological pathways are altered systemically to support faster rates of growth, regardless of the underlying genetic alteration that has caused the altered growth. Microarray analyses were performed on seven individual fish per group of wild type and domestic rainbow trout hybridized (one slide per individual) against a common wild-type RNA pool.
Project description:Atlantic salmon individuals were grown, from fresh water to salt water in tanks on diets with low fish meal (10%) and 1-1.25% total n-3 LC-PUFA levels. Dietary n-3 LC-PUFAs were supplemented by 1) fish oil (FO), 2) Schyzochytrium limacinum biomass (AA). Further, the fish from all treatments were mixed and redistributed in sea cages reared to slaughter (ca. 3kg body weight) on either FO or AA. Transcriptomics analyses in liver and intestinal tissues revealed significant dietary effects on the expression of immune modulating, as well as ion, lipid, protein and xenobiotic metabolism genes.