Oleaginous yeast Rhodotorula toruloides biomass effect on the metabolism of Arctic char (Salvelinus alpinus)

Sustainability issues arise when using fish oil and vegetable oils in fish feed production for aquaculture purposes. Microbial production of single cell oil is a potential alternative as a lipid ingredient in the production of fish feed. In this study, we replaced the vegetable oils with the oleaginous yeast R. toruloides biomass in the diet of Arctic char (S. alpinus) and investigated the effects on health and composition. Measurement of fish growth parameters showed a higher liver weight and hepatosomatic index in the experimental group of fish fed partly with yeast biomass compared to a control group fed a diet with vegetable oils. No significant differences in the lipid content of muscle and liver tissues were found. The fatty acid profiles in the muscle of both fish groups were similar while the experimental fish group had a higher amount of monounsaturated fatty acids in the liver. Histology of livers showed no significant difference in the number of lipid droplets. The size of hepatic lipid droplets seemed to be related to liver fat content. Quantification of metabolites in the liver revealed no differences between the fish groups while plasma metabolites involved in energy pathways such as alanine, 3-hydroxybutyrate, creatinine, serine, betaine, and choline were significantly higher in the experimental fish group

Oleaginous yeast Rhodotorula toruloides biomass effect on the metabolism of Arctic char (Salvelinus alpinus)

Sustainability issues arise when using fish oil and vegetable oils in fish feed production for aquaculture purposes. Microbial production of single cell oil is a potential alternative as a lipid ingredient in the production of fish feed. In this study, we replaced the vegetable oils with the oleaginous yeast R. toruloides biomass in the diet of Arctic char (S. alpinus) and investigated the effects on health and composition. Measurement of fish growth parameters showed a higher liver weight and hepatosomatic index in the experimental group of fish fed partly with yeast biomass compared to a control group fed a diet with vegetable oils. No significant differences in the lipid content of muscle and liver tissues were found. The fatty acid profiles in the muscle of both fish groups were similar while the experimental fish group had a higher amount of monounsaturated fatty acids in the liver. Histology of livers showed no significant difference in the number of lipid droplets. The size of hepatic lipid droplets seemed to be related to liver fat content. Quantification of metabolites in the liver revealed no differences between the fish groups while plasma metabolites involved in energy pathways such as alanine, 3-hydroxybutyrate, creatinine, serine, betaine, and choline were significantly higher in the experimental fish group

STAT3/LKB1 controls metastatic prostate cancer by regulating mTORC1/CREB pathway

Prostate cancer (PCa) is a common and fatal type of cancer in men. Metastatic PCa (mPCa) is a major factor contributing to its lethality, although the mechanisms remain poorly understood. PTEN is one of the most frequently deleted genes in mPCa. Here we show a frequent genomic co-deletion of PTEN and STAT3 in liquid biopsies of patients with mPCa. Loss of Stat3 in a Pten-null mouse prostate model leads to a reduction of LKB1/pAMPK with simultaneous activation of mTOR/CREB, resulting in metastatic disease. However, constitutive activation of Stat3 led to high LKB1/pAMPK levels and suppressed mTORC1/CREB pathway, preventing mPCa development. Metformin, one of the most widely prescribed therapeutics against type 2 diabetes, inhibits mTORC1 in liver and requires LKB1 to mediate glucose homeostasis. We find that metformin treatment of STAT3/AR-expressing PCa xenografts resulted in significantly reduced tumor growth accompanied by diminished mTORC1/CREB, AR and PSA levels. PCa xenografts with deletion of STAT3/AR nearly completely abrogated mTORC1/CREB inhibition mediated by metformin. Moreover, metformin treatment of PCa patients with high Gleason grade and type 2 diabetes resulted in undetectable mTORC1 levels and upregulated STAT3 expression. Furthermore, PCa patients with high CREB expression have worse clinical outcomes and a significantly increased risk of PCa relapse and metastatic recurrence. In summary, we have shown that STAT3 controls mPCa via LKB1/pAMPK/mTORC1/CREB signaling, which we have identified as a promising novel downstream target for the treatment of lethal mPCa

Impact of Reduced Dietary Levels of Eicosapentaenoic Acid and Docosahexaenoic Acid on the Composition of Skin Membrane Lipids in Atlantic Salmon (Salmo salar L.)

acceptedVersio

Identification of metabolites associated with prostate cancer risk : a nested case-control study with long follow-up in the Northern Sweden Health and Disease Study

Background: Prostate cancer is the second most frequently diagnosed cancer in men. Metabolomics can potentially provide new insights into the aetiology of prostate cancer by identifying new metabolic risk factors. This study investigated the prospective association between plasma metabolite concentrations and prostate cancer risk, both overall and by stratifying for disease aggressiveness and baseline age. Methods: In a case-control study nested in the Northern Sweden Health and Disease Study, pre-diagnostic concentrations of 148 plasma metabolites were determined using targeted mass spectrometry- and nuclear magnetic resonance-based metabolomics in 777 prostate cancer cases (follow-up >= 5 years) and 777 matched controls. Associations between prostate cancer risk and metabolite concentrations were investigated using conditional logistic regression conditioned on matching factors (body mass index, age and sample storage time). Corrections for multiple testing were performed using false discovery rate (20%) and Bonferroni. Metabolomics analyses generated new hypotheses, which were investigated by leveragingfood frequency questionnaires(FFQs) and oral glucose tolerance tests performed at baseline. Results: After correcting for multiple testing, two lysophosphatidylcholines (LPCs) were positively associated with risk of overall prostate cancer (all ages and in older subjects). The strongest association was for LPC C17:0 in older subjects (OR = 2.08; 95% CI 1.45-2.98;p < 0.0001, significant also after the Bonferroni correction). Observed associations with risk of overall prostate cancer in younger subjects were positive for glycine and inverse for pyruvate. For aggressive prostate cancer, there were positive associations with six glycerophospholipids (LPC C17:0, LPC C20:3, LPC C20:4, PC ae C38:3, PC ae C38:4 and PC ae C40:2), while there was an inverse association with acylcarnitine C18:2. Moreover, plasma LPC C17:0 concentrations positively correlated with estimated dietary intake of fatty acid C17:0 from the FFQs. The associations between glycerophospholipids and prostate cancer were stronger in case-controls with normal glucose tolerance. Conclusions: Several glycerophospholipids were positively associated with risk of overall and aggressive prostate cancer. The strongest association was observed for LPC C17:0. The associations between glycerophospholipids and prostate cancer risk were stronger in case-controls with normal glucose tolerance, suggesting a link between the glucose metabolism status and risk of prostate cancer

DataSheet1_Oleaginous yeast Rhodotorula toruloides biomass effect on the metabolism of Arctic char (Salvelinus alpinus).pdf

Sustainability issues arise when using fish oil and vegetable oils in fish feed production for aquaculture purposes. Microbial production of single cell oil is a potential alternative as a lipid ingredient in the production of fish feed. In this study, we replaced the vegetable oils with the oleaginous yeast R. toruloides biomass in the diet of Arctic char (S. alpinus) and investigated the effects on health and composition. Measurement of fish growth parameters showed a higher liver weight and hepatosomatic index in the experimental group of fish fed partly with yeast biomass compared to a control group fed a diet with vegetable oils. No significant differences in the lipid content of muscle and liver tissues were found. The fatty acid profiles in the muscle of both fish groups were similar while the experimental fish group had a higher amount of monounsaturated fatty acids in the liver. Histology of livers showed no significant difference in the number of lipid droplets. The size of hepatic lipid droplets seemed to be related to liver fat content. Quantification of metabolites in the liver revealed no differences between the fish groups while plasma metabolites involved in energy pathways such as alanine, 3-hydroxybutyrate, creatinine, serine, betaine, and choline were significantly higher in the experimental fish group.</p

Indication of metabolic inflexibility to food intake in spontaneously overweight Labrador Retriever dogs

Abstract Background Obesity in dogs is an increasing problem associated with morbidity, shortened life span and poor life quality. Overweight dogs exhibit postprandial hyperlipidaemia, highlighting the need to identify potential dysregulations in lipid metabolism. This study investigated metabolites related to lipid metabolism (i.e. acylcarnitines and taurine) and phospholipids in a feed-challenge test and aimed to identify metabolic variations in spontaneously overweight dogs. Twenty-eight healthy male Labrador Retriever dogs were included, 12 of which were classified as lean (body condition score (BCS) 4–5 on a 9-point scale) and 16 as overweight (BCS 6–8). After overnight fasting (14–17 h), fasting blood samples were collected and dogs were fed a high-fat meal followed by postprandial blood sample collection hourly for 4 h. Liquid chromatography-time of flight mass spectrometry (LC-TOFMS) was used to identify plasma metabolites and phospholipids. Multivariate models, mixed model repeated measures and linear regression analyses were used for data interpretation. Results In all dogs, propionylcarnitine, stearoylcarnitine and nine phospholipids increased in response to food intake, while vaccenylcarnitine decreased (P ≤ 0.005 for all). Overall, carnitine and acetylcarnitine signal areas in the feed-challenge test were lower in overweight dogs (P ≤ 0.004). Notably, fasting plasma acetylcarnitine was lower in overweight dogs than in lean dogs (P = 0.001) and it did not change in response to feeding. The latter finding was in contrast to the decreased acetylcarnitine signal area found in lean dogs at one hour postprandially (P  6) than in lean dogs (P < 0.05). Conclusions Plasma carnitine status was overall lower in spontaneously overweight dogs than in lean dogs in this cohort of healthy Labrador Retriever dogs, indicating a potential carnitine insufficiency in the overweight group. The acetylcarnitine response in overweight dogs indicated decreased fatty acid oxidation at fasting and metabolic inflexibility to food intake. Further studies on metabolic inflexibility and its potential role in the metabolism of overweight dogs are warranted

Serum metabolomics analysis reveals increased lipid catabolism in mildly hyperbilirubinemic Gilbert's syndrome individuals

Background: The protective role of mildly elevated bilirubin against CVD and diabetes mellitus type 2 (DMT2) is associated with a favorable lipid phenotype. As the mechanistic understanding of this protection in humans remains elusive, we aimed to assess the metabolomics profile of mildly hyperbilirubinemic (Gilbert's syndrome; GS) individuals especially targeting lipid catabolism. Methods and results: Using NMR serum metabolomics of 56 GS individuals and 56 age and gender-matched healthy controls, GS individuals demonstrated significantly greater concentrations of acetylcarnitine (+20%, p < 0.001) and the ketone bodies, 3-hydroxybutyric acid (+132%, p < 0.001), acetoacetic acid (+95%, p < 0.001) and acetone (+46%, p < 0.001). Metabolites associated with an increased mitochondrial lipid metabolism such as citrate (+15%, p < 0.001), anaplerotic amino acid intermediates and creatinine were significantly greater and creatine significantly reduced in GS individuals. Stimulators of lipid catabolism including AMPK (+59%, p < 0.001), pPPAR alpha (+24%, p < 0.001) and T3 (+9%, p = 0.009) supported the metabolomics data while concomitantly blood glucose and insulin (-33%, p = 0.002) levels were significantly reduced. We further showed that the increased lipid catabolism partially mediates the favorable lipid phenotype (lower triglycerides) of GS individuals. Increased trimethylamine (+35%, p < 0.001) indicated changes in trimethylamine metabolism, an emerging predictor of metabolic health. Conclusion: We showed an enhanced lipid catabolism in mildly hyperbilirubinemic individuals, novel evidence as to why these individuals are leaner and protected against chronic metabolic diseases emphasizing bilirubin to be a promising future target in obese and dyslipidemia patients. (c) 2021 Published by Elsevier Inc