Effect of L-carnitine administration on lipid and metabolite content in sheep infraspinatus muscle after tendon release
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ABSTRACT:
INSTRUMENT(S): Liquid Chromatography MS - positive - HILIC, Liquid Chromatography MS - negative - HILIC
SUBMITTER: Martin Flück
PROVIDER: MTBLS1490 | MetaboLights | 2020-07-20
REPOSITORIES: MetaboLights
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Project description:Aims/hypothesis: While lipid deposition in skeletal muscle is considered to be involved in obesity-associated insulin resistance, neutral intramyocellular lipid (IMCL) accumulation per se does not necessarily induce insulin resistance. We previously demonstrated that overexpression of the lipid droplet coat protein perilipin 2 augments intramyocellular lipid content while improving insulin sensitivity. Another member of the perilipin family, perilipin 5 (PLIN5), is predominantly expressed in oxidative tissues like skeletal muscle. Here we investigated the effects of PLIN5 overexpression M-bM-^@M-^S in comparison with effects of PLIN2 M-bM-^@M-^S on skeletal muscle lipid levels, gene expression profiles and insulin sensitivity. Methods: Gene electroporation was used to overexpress PLIN5 in tibialis anterior muscle of rats fed a high fat diet. Eight days after electroporation, insulin-mediated glucose uptake in skeletal muscle was measured by means of a hyperinsulinemic euglycemic clamp. Electron microscopy, fluorescence microscopy and lipid extractions were performed to investigate IMCL accumulation. Gene expression profiles were obtained using microarrays. Results: TAG storage and lipid droplet size increased upon PLIN5 overexpression. Despite the higher IMCL content, insulin sensitivity was not impaired and DAG and acylcarnitine levels were unaffected. In contrast to the effects of PLIN2 overexpression, microarray data analysis revealed a gene expression profile favoring FA oxidation and improved mitochondrial function. Conclusions/interpretation: Both PLIN2 and PLIN5 increase neutral IMCL content without impeding insulin-mediated glucose uptake. As opposed to the effects of PLIN2 overexpression, overexpression of PLIN5 in skeletal muscle promoted expression of a cluster of genes under control of PPARM-NM-1 and PGC1M-NM-1 involved in FA catabolism and mitochondrial oxidation. Rats received a high fat diet for 3 weeks; 2 weeks after start of the diet intervention Plin5 (OXPAT) or Plin2 (ADRP) were overexpressed in either the right or left tibialis anterior muscle. One week later pooled tibialis anterior muscle samples were analysed on microarrays.
2013-01-29 | E-GEOD-43832 | biostudies-arrayexpress
Project description:Transcripts were measured in infraspinatus muscle before (PRE) and after 16 weeks of tendon release (TR) and 6 weeks of subsequent repair (END) in the operated and contralateral (END-CC) muscle. A group of animals received intramuscular injections of nandrolone starting with the surgery (N22W). In another group injection of nandrolone was started at the time of tendon repair (N6W). The CONTROL group received no nandrolone.
2016-12-31 | GSE80374 | GEO
Project description:Muscle is a target of growth hormone (GH) action and a major contributor to whole body metabolism. Little is known about how GH regulates metabolic process in muscle or the extent to which muscle contributes to changes in whole body substrate metabolism during GH treatment. To identify GH-responsive genes that regulate substrate metabolism in muscle, we studied six hypopituitary men who underwent whole body metabolic measurement and muscle biopsies before and after two weeks of GH treatment (0.5mg/day). Transcript profiles of four subjects were analysed using Affymetrix GeneChips. Serum insulin-like growth factor I (IGF-I), procollagens I and III were measured by RIA. GH increased serum IGF-I, procollagens I and III, enhanced whole body lipid oxidation, reduced carbohydrate oxidation, and stimulated protein synthesis. It induced gene expression of IGF-I and collagens in muscle. GH reduced expression of several enzymes regulating lipid oxidation and energy production. It reduced calpain 3, increased ribosomal protein L38 expression, and displayed mixed effects on genes encoding myofibrillar proteins. It increased expression of circadian gene CLOCK, and reduced that of PERIOD. In summary, GH exerted concordant effects on muscle expression and blood levels of IGF-I and collagens. It induced changes in genes regulating protein metabolism in parallel with a whole body anabolic effect. The discordance between muscle gene expression profiles and metabolic responses suggests that muscle is unlikely to contribute to GH-induced stimulation of whole body energy and lipid metabolism. GH may regulate circadian function in muscle by modulating circadian gene expression with possible metabolic consequences.
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Project description:Urolithin A (UA) is a natural dietary, microflora derived, metabolite shown to stimulate mitophagy and improve muscle health in old animals and pre-clinical models of aging. UA was administered for 28-day in a first-in-human clinical trial to sedentary elderly subjects. Muscle biopsies were collected before the first dosing, and at the end of the 28-day period, under fasted conditions. Gene expression was measured by microarray. Gene-set enrichment analysis of the gene expression data showed that UA increased the transcription of mitochondrial related genesets. These observed effects on mitochondrial biomarkers show that UA induces a molecular signature of improved mitochondrial and cellular health following regular oral consumption in humans.
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Project description:Intramuscular fat (IMF) storage is a biological process with strong impact on nutritional and technological properties of meat, and also with relevant consequences on human health. The genetic architecture of IMF content and composition phenotypes has been thoroughly studied in pigs through the identification of quantitative trait loci (QTL) and the estimation of genetic parameters. A question that has not been elucidated yet is if the genetic determinants of IMF-related phenotypes are muscle specific or, conversely, they have broad effects on the whole skeletal muscle compartment. We have addressed this question by generating lipid QTL maps for two muscles with a high commercial value, gluteus medius (GM) and longissimus thoracis et lumborum (LTL), in a Duroc commercial population (N=350). As a complementary approach, we have analysed the mRNA expression pattern of both muscles at a whole genome scale. The lack of concordance between the GM and LTL QTL maps evidenced that the effects of polymorphisms influencing IMF, cholesterol and fatty acids contents are modulated to some extent by complex spatial factors related with muscle location, metabolism and function. This interpretation was supported by our finding that genes influencing cell differentiation, muscle development and function and lipid metabolism are differentially expressed between muscles. These results have important implications on the implementation of genomic selection schemes aimed to improve the lipid profile of swine meat. Moreover, they confirm pigs as a valuable model to dissect the genetic basis of muscle lipid phenotypes of clinical interest in human. Longissimus thoracis et lumborum muscle tissue from 10 high and 9 low fattening Duroc pigs were compared in this study.
2010-12-01 | E-GEOD-25708 | biostudies-arrayexpress
Project description:Aims/hypothesis: While lipid deposition in skeletal muscle is considered to be involved in obesity-associated insulin resistance, neutral intramyocellular lipid (IMCL) accumulation per se does not necessarily induce insulin resistance. We previously demonstrated that overexpression of the lipid droplet coat protein perilipin 2 augments intramyocellular lipid content while improving insulin sensitivity. Another member of the perilipin family, perilipin 5 (PLIN5), is predominantly expressed in oxidative tissues like skeletal muscle. Here we investigated the effects of PLIN5 overexpression – in comparison with effects of PLIN2 – on skeletal muscle lipid levels, gene expression profiles and insulin sensitivity. Methods: Gene electroporation was used to overexpress PLIN5 in tibialis anterior muscle of rats fed a high fat diet. Eight days after electroporation, insulin-mediated glucose uptake in skeletal muscle was measured by means of a hyperinsulinemic euglycemic clamp. Electron microscopy, fluorescence microscopy and lipid extractions were performed to investigate IMCL accumulation. Gene expression profiles were obtained using microarrays. Results: TAG storage and lipid droplet size increased upon PLIN5 overexpression. Despite the higher IMCL content, insulin sensitivity was not impaired and DAG and acylcarnitine levels were unaffected. In contrast to the effects of PLIN2 overexpression, microarray data analysis revealed a gene expression profile favoring FA oxidation and improved mitochondrial function. Conclusions/interpretation: Both PLIN2 and PLIN5 increase neutral IMCL content without impeding insulin-mediated glucose uptake. As opposed to the effects of PLIN2 overexpression, overexpression of PLIN5 in skeletal muscle promoted expression of a cluster of genes under control of PPARα and PGC1α involved in FA catabolism and mitochondrial oxidation.
2013-01-29 | GSE43832 | GEO
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Project description:To identify insulin responsive genes in humans, in the first protocol, skeletal muscle biopsies from six non-diabetic subjects were obtained before and after a two-hour of hyperinsulinaemic (infusion rate 40 mU/m2/min) euglycemic clamp. A variable infusion of glucose (180 g/l) enriched with tritiated glucose (100 μCi/500 ml) maintained euglycemia during insulin infusion, with monitoring of plasma glucose concentration every 5 to 10 min during the basal and clamp periods using an automated glucose oxidation method (Glucose Analyzer 2, Beckman Instruments, Fullerton, CA). In the second protocol, skeletal muscle biopsies from six non-diabetic subjects were obtained before and after a 3-hour hyperinsulinemic (infusion rate 40 mU/m2/min) euglycemic clamp in order to increase the effects of insulin on gene expression. A variable infusion of glucose (180 g/l) was used to maintain euglycemia during insulin infusion with monitoring of plasma glucose concentration every 5 to 10 min using an automated glucose oxidation method (Glucose Analyzer 2, Beckman Instruments, Fullerton, CA). Keywords: dose response The muscle biopsies were obtained from the vastus lateralis muscle under local anesthesia before and after hyperinsulinaemic (infusion rate 40 mU/m2/min) euglycemic clamp
2007-03-01 | E-GEOD-7146 | biostudies-arrayexpress
Project description:Intramuscular fat (IMF) storage is a biological process with strong impact on nutritional and technological properties of meat, and also with relevant consequences on human health. The genetic architecture of IMF content and composition phenotypes has been thoroughly studied in pigs through the identification of quantitative trait loci (QTL) and the estimation of genetic parameters. A question that has not been elucidated yet is if the genetic determinants of IMF-related phenotypes are muscle specific or, conversely, they have broad effects on the whole skeletal muscle compartment. We have addressed this question by generating lipid QTL maps for two muscles with a high commercial value, gluteus medius (GM) and longissimus thoracis et lumborum (LTL), in a Duroc commercial population (N=350). As a complementary approach, we have analysed the mRNA expression pattern of both muscles at a whole genome scale. The lack of concordance between the GM and LTL QTL maps evidenced that the effects of polymorphisms influencing IMF, cholesterol and fatty acids contents are modulated to some extent by complex spatial factors related with muscle location, metabolism and function. This interpretation was supported by our finding that genes influencing cell differentiation, muscle development and function and lipid metabolism are differentially expressed between muscles. These results have important implications on the implementation of genomic selection schemes aimed to improve the lipid profile of swine meat. Moreover, they confirm pigs as a valuable model to dissect the genetic basis of muscle lipid phenotypes of clinical interest in human.
2010-12-01 | GSE25708 | GEO
Project description:Despite this large body of evidence from clinical studies that an improvement of carnitine status has beneficial effects on metabolic health, serious safety concerns with carnitine supplementation have been raised based on the recent observation that longterm carnitine supplementation (from weaning to 5 mo of age) in a transgenic mouse model of atherosclerosis (Apoe-/- mice) promotes atherosclerosis through gut microbiota-dependent formation of trimethylamine (TMA) and subsequent hepatic conversion into proatherogenic TMA-N-oxide (TMAO) (Koeth et al., 2013). In addition, Lu et al. (2017) found that carnitine supplementation to normal mice for 3 mo induces oxidative stress, liver inflammation, liver lipid accumulation and even liver damage as well as hypercholesterinemia. However, it has to be mentioned that the carnitine dose administered to the mice in the abovementioned studies was extremely high. In order to address whether safety concerns are founded under conditions of longterm supplementation of a carnitine dose used in clinical trials, the present study aimed to investigate the effect of almost lifelong daily administration of a carnitine-supplemented diet (1 g/kg diet) to mice from weaning to 18 mo of age. Considering a body weight of 50 g for an adult mice and a daily feed intake of 5 g, the daily intake of this diet results in a daily carnitine dose of 100 mg/kg body weight which better reflects the dose used in clinical trials. In order to evaluate possible detrimental effects of carnitine supplementation, we investigated parameters of lipid metabolism and stress signaling pathways in the liver and performed a genome-wide transcriptome analysis of skeletal muscle in the mice at advanced age.
2018-09-19 | GSE120120 | GEO