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.
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:Omega - 3 fatty acids of marine origin exert beneficial effects on lipid metabolism and can protect against insulin resistance in high fat diet (HFD)-fed animals. Simultaneously, recent studies showed that different lipid forms could have numerous consequences regarding the regulation of energy balance, nutrient absorption, and substrate metabolism. Indeed, when omega-3 was provided as triglycerides (TG, i.e. fish oil), it induced dose-dependently the expression of genes involved in lipid metabolism as well as fatty acid oxidation in small intestine of C57BL/6 mice fed various HFDs. As the underlying mechanism(s) explaining the differences in EPA/DHA bioavailability among various lipid forms of Omega-3 is not entirely clear, we performed a mouse study (n=8 per group) using purified HFDs with control HFD based on corn oil (cHF) and part of the lipids were replaced by omega-3 fish lipids in different forms: as either TG (cHF-F), marine phospholipids (PL; Krill oil, given at two different doses Krill-low (Krill-L) and Krill-high (Krill-H)), and as wax esters in the extract from the zooplankton Calanus finmarchicus (Calanus oil CAL-L representing same omega-3 levels as Krill-L diet). As a healthy control we fed a subset of mice standard chow (STD). All mice were fed their diet for 8 weeks and after sacrifice, whole small intestine was isolated, frozen and used for RNA isolation and microarray gene expression analysis using 8x60K Agilent arrays. Results showed that PL-H versus control cHFc induced specifically metabolic lipid pathways, while TG and PL-L mainly affected cytoskeleton regulation.
Project description:Krill oil is a dietary supplement derived from Antarctic krill; a small crustacean found in the ocean. Krill oil is a rich source of omega-3 fatty acids, specifically eicosapentaenoic acid and docosahexaenoic acid, as well as the antioxidant astaxanthin. The aim of this study was to investigate the effects of krill oil supplementation, compared to placebo oil (high oleic sunflower oil added astaxanthin), in vivo on energy metabolism and substrate turnover in skeletal muscle cells. Skeletal muscle cells (myotubes) were obtained before and after a 7-week krill oil or placebo oil intervention, and glucose and oleic acid metabolism and leucine accumulation, as well as effects of different stimuli in vitro, were studied in the myotubes. In vivo intervention with krill oil increased oleic acid oxidation and leucine accumulation in skeletal muscle cells, however no effects were observed on glucose metabolism. The krill oil-intervention-induced increase in oleic acid oxidation correlated negatively with changes in serum low-density lipoprotein (LDL) concentration. In addition, myotubes were also exposed to krill oil in vitro. The in vitro study revealed that 24 h of krill oil treatment increased both glucose and oleic acid metabolism, enhancing energy substrate utilization. Transcriptomic analysis comparing myotubes obtained before and after krill oil-supplementation identified differentially expressed genes associated with e.g. glycolysis/gluconeogenesis, metabolic pathways and calcium signaling pathway, while proteomic analysis demonstrated upregulation of e.g. LDL-receptor in myotubes obtained after krill oil intervention. These findings suggest that krill oil intervention promotes increased fuel metabolism and protein synthesis in human skeletal muscle cells, with potential implications for metabolic health.
Project description:Krill oil is a dietary supplement derived from Antarctic krill; a small crustacean found in the ocean. Krill oil is a rich source of omega-3 fatty acids, specifically eicosapentaenoic acid and docosahexaenoic acid, as well as the antioxidant astaxanthin. The aim of this study was to investigate the effects of krill oil supplementation, compared to placebo oil (high oleic sunflower oil added astaxanthin), in vivo on energy metabolism and substrate turnover in skeletal muscle cells. Skeletal muscle cells (myotubes) were obtained before and after a 7-week krill oil or placebo oil intervention, and glucose and oleic acid metabolism and leucine accumulation, as well as effects of different stimuli in vitro, were studied in the myotubes. In addition, myotubes were also exposed to krill oil in vitro. The in vitro study revealed that 24 h of krill oil treatment increased both glucose and oleic acid metabolism, enhancing energy substrate utilization. In vivo intervention with krill oil increased oleic acid oxidation and leucine accumulation in skeletal muscle cells, however no effects were observed on glucose metabolism. The krill oil-intervention-induced increase in oleic acid oxidation correlated negatively with changes in serum low-density lipoprotein (LDL) concentration. Transcriptomic analysis comparing myotubes obtained before and after krill oil-supplementation identified differentially expressed genes associated with e.g. glycolysis/gluconeogenesis, metabolic pathways and calcium signaling pathway, while proteomic analysis demonstrated upregulation of e.g. LDL-receptor. These findings suggest that krill oil intervention promotes increased fuel metabolism and protein synthesis in human skeletal muscle cells, with potential implications for metabolic health.
Project description:Purpose: Supplementation with krill oil has shown effects on whole-body lipid and glucose metabolism, as well as on skeletal muscle strength and function. We previously showed that krill oil intervention in vivo promoted fatty acid metabolism and protein synthesis in cultured human myotubes in a two-dimensional (2D) model. The aim of this study was to explore the effects of krill oil supplementation in vivo in a 3D myosphere model and to compare the 3D and 2D models. Methods: Myospheres were formed from myoblasts obtained before and after 7 weeks of in vivo krill oil intervention. Glucose and oleic acid metabolism were assessed, and transcriptomic and proteomic analyses were performed. Results: In vivo intervention with krill oil increased glucose metabolism in myospheres, while no effect was observed on fatty acid metabolism. Transcriptomic analyses of myospheres after krill oil intervention showed increased expression of genes involved in pathways like motor proteins and hypertrophy, as well as in calcium signaling, of which motor proteins and hypertrophy pathways have not been described in 2D myotube cultures. Proteomic analyses after krill oil intervention showed increased expression of proteins in glycolysis/gluconeogenesis and fatty acid degradation. Comparison of proteins expressed in the 3D myosphere model and a 2D myotube model at the basal level showed that in myospheres, mitochondrial gene expression and translation dominated, while in 2D cultures, mitochondrial organization and response to oxidative stress were more important. Conclusion: These findings suggest that in vivo krill oil intervention induces different metabolic effects when comparing 3D and 2D cultures. In contrast to the 2D model, data obtained with the 3D model showed gene expression changes that are more compatible with previously observed results in vivo concerning skeletal muscle motoric function. Hence, the 3D model might better reflect krill oil-induced modifications in skeletal muscle performance in vivo than the 2D model.
2025-07-30 | GSE291925 | GEO
Project description:Effects and mechanisms of fish oil replacement by krill oil
Project description:There is accumulating evidence that interfering with the basic aging mechanisms can enhance healthy longevity. Many cellular processes contribute to aging and are referred to as “hallmarks of aging”; by presumption, interventional/therapeutic strategies targeting on multiple ageing hallmarks could be more effective to delay ageing than targeting on one hallmark. While the health-promoting qualities of marine oils have been extensively studied, the underlying molecular mechanisms are not fully understood. Lipid extracts from Antarctic krill are rich in long-chain omega-3 fatty acids (eicosapentaenoic acid/EPA and docosahexaenoic acid/DHA), choline, and astaxanthin. Here, we investigated whether krill oil promotes healthy aging in the small roundworm C. elegans. We show that krill oil rewires distinct gene expression programs that contribute to attenuate several aging hallmarks, including oxidative stress, proteotoxic stress, senescence, genomic instability, and mitochondrial dysfunction. In a C. elegans model of Parkinson´s disease, krill oil protects dopaminergic neurons from aging-related degeneration, decreases alpha synuclein aggregation, and improves dopamine-dependent behavior and cognition. Mechanistically, krill oil increases neuronal resilience through temporal transcriptome rewiring to promote anti-oxidative stress and inflammation via healthspan regulating transcription factors such as SNK-1. However, also krill oil promotes DA neuron survival through regulation of synaptic transmission and neuronal functions via PBO-2 and RIM-1. Collectively, krill oil rewires global gene expression programs and promotes healthy aging via abrogating multiple ageing hallmarks, shedding light on further pre-clinical and clinical explorations.