Carnitine synthesis and uptake into cells are stimulated by fasting in pigs as a model of nonproliferating species

Ringseis, Robert; Wege, Nicole; Wen, Gaiping; Rauer, Christine; Hirche, Frank; Kluge, H.; Eder, Klaus

doi:10.1016/j.jnutbio.2008.07.012

Cited by 48 publications

(39 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Kidney, one of the sites where carnitine is synthesized and where reabsorption of carnitine takes place, is therefore known as a regulator of the whole body carnitine pool (19,21,33). Interestingly, the carnitine flux in kidney did not reflect clear production of carnitine from reabsorption.…”

Section: E260 Transorgan Acylcarnitine Fluxes In a Porcine Modelmentioning

confidence: 98%

“…It is well established that most carnitine is absorbed from the diet, which enters the circulation via the gut. Studies in pigs have shown that PPAR␣ and subsequent carnitine palmitoyl transferase-1 activity are upregulated upon fasting (21). This PPAR␣ activation can be necessary to orchestrate lipid oxidation pathways in the intestine itself in the fasted state but might facilitate carnitine uptake as well.…”

Section: E260 Transorgan Acylcarnitine Fluxes In a Porcine Modelmentioning

confidence: 99%

“…In general, most processes in lipid metabolism and FAO are orchestrated by peroxisome proliferator-activated receptor-␣ (PPAR␣) in pigs, rodents, and humans (4). Although gene expression does not necessarily reflect enzyme activities, fatty acid flux, or partitioning, the expression of PPAR␣ is comparable between pigs and humans but higher in rodents (13,21,22). As for humans, it has been demonstrated that fasting causes an upregulation of the PPAR␣ target genes involved in mitochondrial and peroxisomal ␤-oxidation as well as ketogenesis and gluconeogenesis in pig liver (4).…”

mentioning

confidence: 99%

“…Additionally, fasting increased carnitine levels in porcine liver and kidney along with a higher expression of butyrobetaine dioxygenase (BBD). The latter suggests higher rates of carnitine biosynthesis in these tissues, which might be regulated by fasting-induced PPAR␣ expression (21,22). We studied healthy, lean pigs to investigate acylcarnitine metabolism in a normal physiological setting to use as a starting point…”

mentioning

confidence: 99%

See 3 more Smart Citations

Transorgan fluxes in a porcine model reveal a central role for liver in acylcarnitine metabolism

Schooneman

Have

Vlies

et al. 2015

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

-Acylcarnitines are derived from mitochondrial acyl-CoA metabolism and have been associated with diet-induced insulin resistance. However, plasma acylcarnitine profiles have been shown to poorly reflect whole body acylcarnitine metabolism. We aimed to clarify the individual role of different organ compartments in whole body acylcarnitine metabolism in a fasted and postprandial state in a porcine transorgan arteriovenous model. Twelve cross-bred pigs underwent surgery where intravascular catheters were positioned before and after the liver, gut, hindquarter muscle compartment, and kidney. Before and after a mixed meal, we measured acylcarnitine profiles at several time points and calculated net transorgan acylcarnitine fluxes. Fasting plasma acylcarnitine concentrations correlated with net hepatic transorgan fluxes of free and C2-and C16-carnitine. Transorgan acylcarnitine fluxes were small, except for a pronounced net hepatic C2-carnitine production. The peak of the postprandial acylcarnitine fluxes was between 60 and 90 min. Acylcarnitine production or release was seen in the gut and liver and consisted mostly of C2-carnitine. Acylcarnitines were extracted by the kidney. No significant net muscle acylcarnitine flux was observed. We conclude that liver has a key role in acylcarnitine metabolism, with high net fluxes of C2-carnitine both in the fasted and fed state, whereas the contribution of skeletal muscle is minor. These results further clarify the role of different organ compartments in the metabolism of different acylcarnitine species.acylcarnitines; pigs; fatty acid oxidation; mixed-meal test ACYLCARNITINES ARE INTERMEDIATES of mitochondrial acyl-CoA metabolism, which have gained much attention as markers of inherited metabolic diseases (34) and more recently for their possible involvement in diet-induced insulin resistance and glucose intolerance (2,12,14,16, 18,24). Acylcarnitines are carboxylic acids of different chain lengths derived from different substrates (e.g., fatty acids, amino acids or acetyl-CoA) that are transesterified from CoA to L-carnitine, enabling them to enter or exit the mitochondrion (33). Exchange of acylcarnitines also occurs over the cell membrane. This leads to a specific acylcarnitine profile in plasma composed of acylcarnitines originating from and consumed by the different organs and compartments where the respective acyl-CoAs are metabolized (33). Historically, acylcarnitine profiles have been measured to detect mitochondrial fatty acid oxidation (FAO) disorders (34). More recently, studies have discussed alterations in the acylcarnitine profile, measured mostly in plasma, in relation to deranged FAO and glucose intolerance or insulin resistance (2,12,14). Because increased acylcarnitine levels correlated with markers of glucose intolerance in obesity, acylcarnitines were proposed to potentially induce insulin resistance (10,11,26).However, we have shown previously that the plasma acylcarnitine profile should be interpreted with caution, as it does not reflect the acylcarniti...

show abstract

Section: E260 Transorgan Acylcarnitine Fluxes In a Porcine Modelmentioning

confidence: 98%

Section: E260 Transorgan Acylcarnitine Fluxes In a Porcine Modelmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Transorgan fluxes in a porcine model reveal a central role for liver in acylcarnitine metabolism

Schooneman

Have

Vlies

et al. 2015

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

show abstract

“…Therefore, release of non-esterified fatty acids (NEFAs) from adipose tissue, the natural ligand of this isoform, activates PPARα expression resulting in the expression of genes involved in the activation and β-oxidation of FAs [12]. Ligand activation of PPARα occurring with energy deprivation, such as during fasting and caloric restriction, also stimulates carnitine biosynthesis and uptake mechanisms into tissues to facilitate FA oxidation [13-15]. Recently, we have reported similar changes with chronic exercise training where BBH expression increased the carnitine concentration in plasma of rat [16].…”

Section: Introductionmentioning

confidence: 99%

Acute Exercise Stimulates Carnitine Biosynthesis and OCTN2 Expression in Mouse Kidney

Cusimano¹,

Carlson²,

Tamura³

2017

Kidney Blood Press Res

View full text Add to dashboard Cite

Background/Aims: Carnitine is essential for the transport of long-chain FAs (FA) into the mitochondria for energy production. During acute exercise, the increased demand for FAs results in a state of free carnitine deficiency in plasma. The role of kidney in carnitine homeostasis after exercise is not known. Methods: Swiss Webster mice were sacrificed immediately after a 1-hour moderate intensity treadmill run, and at 4-hours and 8-hours into recovery. Non-exercising mice served as controls. Plasma was analyzed for carnitine using acetyltransferase and [¹⁴C] acetyl-CoA. Kidney was removed for gene and protein expression of butyrobetaine hydroxylase (γ-BBH), organic cation transporter (OCTN2), and peroxisome proliferator-activated receptor (PPARα), a regulator of fatty acid oxidation activated by FAs. Results: Acute exercise caused a decrease in plasma free carnitine levels. Rapid return of free carnitine to control levels during recovery was associated with increased γ-BBH expression. Both mRNA and protein levels of OCTN2 were detected in kidney after exercise and during recovery, suggesting renal transport mechanisms were stimulated. These changes were accompanied with a reciprocal increase in PPARα protein expression. Conclusions: Our results show that the decrease in free carnitine after exercise rapidly activates carnitine biosynthesis and renal transport mechanism in kidney to establish carnitine homeostasis.

show abstract

Monocarboxylate transporter 1 and CD147 are up‐regulated by natural and synthetic peroxisome proliferator‐activated receptor α agonists in livers of rodents and pigs

König

Fischer

Schlotte

et al. 2010

Molecular Nutrition Food Res

Self Cite

View full text Add to dashboard Cite

Monocarboxylate transporter (MCT)-1 mediates the transport of ketone bodies and other monocarboxylic acids across the plasma membrane. MCT1 is up-regulated by peroxisome proliferator-activated receptor (PPAR)-alpha, a transcription factor that mediates the adaptive response to fasting by up-regulation of genes involved in fatty acid oxidation and ketogenesis. Here, we show for the first time that MCT1 is up-regulated by dietary natural PPAR-alpha agonists. Both, an oxidized fat and conjugated linoleic acids increased MCT1 mRNA concentration in the liver of rats. Also, in the liver of pigs as non-proliferating species MCT1 was up-regulated upon PPAR-alpha activation by clofibrate, oxidized fat and fasting. Concomitant with up-regulation of MCT1, mRNA level of CD147 was increased in livers of rats and pigs. CD147 is a plasma membrane glycoprotein that is required for translocation and transport activity of MCT1. CD147 mRNA increase upon PPAR-alpha activation could not be observed in mice lacking PPAR-alpha, which also fail in up-regulation of MCT1 indicating a co-regulation of MCT1 and CD147. Analysis of the 5'-flanking region of mouse MCT1 gene by reporter gene assay revealed that promoter activity of mouse MCT1 was not induced by PPAR-alpha, indicating that the 5'-flanking region is not involved in MCT1 regulation by PPAR-alpha.

show abstract

Carnitine synthesis and uptake into cells are stimulated by fasting in pigs as a model of nonproliferating species

Cited by 48 publications

References 36 publications

Transorgan fluxes in a porcine model reveal a central role for liver in acylcarnitine metabolism

Transorgan fluxes in a porcine model reveal a central role for liver in acylcarnitine metabolism

Acute Exercise Stimulates Carnitine Biosynthesis and OCTN2 Expression in Mouse Kidney

Monocarboxylate transporter 1 and CD147 are up‐regulated by natural and synthetic peroxisome proliferator‐activated receptor α agonists in livers of rodents and pigs

Contact Info

Product

Resources

About