F.R. Van der Leij

Hogeschool Inholland · Research and Innovation Centre Agri, Food & Life Sciences

Background Physical weakness is a key component of frailty, and is highly prevalent in older adults. While females have a higher prevalence and earlier onset, sex differences in the development of frailty-related physical weakness are hardly studied. Therefore, we investigated the intramuscular changes that differentiate between fit and weak older...

Sex differences in muscle aging are poorly understood, but could be crucial for the optimization of sarcopenia-related interventions. To gain insight into potential sex differences in muscle aging, we recruited young (23 ± 2 years, 13 males and 13 females) and old (80 ± 3.5 years, 28 males and 26 females) participants. Males and females in both gro...

Understanding taste is key for optimizing the palatability of seaweeds and other non‐animal‐based foods rich in protein. The lingual papillae in the mouth hold taste buds with taste receptors for the five gustatory taste qualities. Each taste bud contains three distinct cell types, of which Type II cells carry various G protein‐coupled receptors th...

Protein transition trends may indicate different regional developments. With increasing economic levels, diets are globally shifting from plant-based to animal proteins. However, in many economically established regions the opposite occurs due to people's care for the environment and concern for health. This study investigated the relationships bet...

Carnitine: iedereen heeft het, maar bijna niemand weet het. Wat is carnitine eigenlijk? Wat doet het en wat gebeurt er als het in meerdere of mindere mate aanwezig is in het lichaam? Zes studenten van de opleiding Food Commerce & Technology van Hogeschool Inholland deden, onder supervisie van een docent- onderzoeker, een literatuuronderzoek. VOEDIN...

We developed inspiring learning materials to achieve awareness in secondary schools in the Netherlands. A Genomics Cookbook with food metaphors to explain biological principles is highly appreciated by both teachers and students. It is a way to increase influx into green colleges and universities, and thereby efflux to the agrifood sector.

This study tested the hypothesis that in human aging, a decreased intramuscular acylcarnitine status is associated with (pre‐)frailty, reduced physical performance, and altered mitochondrial function. We used a cross‐sectional study design with well‐matched fit and (pre‐)frail old males and females, using young males and females as healthy controls...

CPT2 and CPT1 are the most distantly related carnitine acyltransferases and the subcellular mitochondrial location of CPT2 and CPT1 switched during evolution. ChAT is closely related to CrAT but evolved further to become choline specific. Five extra CPT1-like genes exist in Caenorhabditis elegans. CPT1C resulted from positive and/or relaxed evol...

Carnitine/choline acyltransferases play diverse roles in energy metabolism and neuronal signalling. Our knowledge of their evolutionary relationships, important for functional understanding, is incomplete. Therefore, we aimed to determine the evolutionary relationships of these eukaryotic transferases. We performed extensive phylogenetic and intron...

Geriatric patients are often malnourished. Promising results have been obtained in the Medical Centre Leeuwarden, The Netherlands. Students of University of Applied Sciences Van Hall Larenstein collaborated with Royal Koopmans Meelfabrieken and Van der Zee Bakeries. A novel enriched bread was produced and a clinical trial was carried out to monitor...

Shrimp shells make up about two-thirds of the total shrimp supply and were often considered as waste, with applications as fish feed at best. Nowadays, human food applications are within reach. This paper describes two approaches that we chose to develop novel foods from shrimp shells. Broth cubes were succesfully developed to provide tasty bases f...

The carnitine palmitoyl transferase (CPT) system is a multiprotein complex with catalytic activity localized within a core represented by CPT1 and CPT2 in the outer and inner membrane of the mitochondria, respectively. Two proteins, the acyl-CoA synthase and a translocase also form part of this system. This system is crucial for the mitochondrial b...

Het onderwerp van deze inaugurele rede is overvoeding en ondervoeding. Daarnaast loopt er een rode draad door dit betoog: het grote belang van de verwevenheid van onderzoek met onderwijs.

In this study we review relevant pathways with regard to the production of poly(3-hydroxyalkanoates) (PHA) with medium chain length monomers in higher plants. On the basis of what is known of the genetics and the biochemistry of PHA formation in bacteria, and of fatty acid metabolism in various organisms, a number of possibilities for PHA productio...

Because L-carnitine (L-CAR) is a potential substitute for neonatal dexamethasone (DEX) with respect to the prevention of long-term side effects, rats were treated on d 1, 2, and 3 after birth with saline, DEX, L-CAR, half the dose of DEX, and L-CAR + half DEX. DEX led to growth retardation, increased mortality, and severe kidney damage at 50 wk of...

Insulin sensitizers like metformin generally act through pathways triggered by adenosine monophosphate-activated protein kinase. Carnitine palmitoyltransferase 1 (CPT1) controls mitochondrial beta-oxidation and is inhibited by malonyl-CoA, the product of acetyl-CoA carboxylase (ACC). The adenosine monophosphate-activated protein kinase-ACC-CPT1 axi...

Dexamethasone (Dex), for prevention of chronic lung disease in preterm infants, showed potential negative long-term effects. Studies regarding long-term cardiovascular effects are lacking. We investigated possible histopathological myocardial changes after neonatal Dex in the young and adult rat heart. Rats were treated with Dex on d 1, 2, and 3 (0...

Literature suggests that glucocorticoid (GC) exposure during early life may have long-term consequences into adult life. GCs are known to influence hepatic bile acid synthesis and their transport within the enterohepatic circulation. This study addresses effects of early postnatal exposure to GC on hepatic expression of key genes in bile acid metab...

Glucocorticoids (GCs) are widely used to prevent chronic lung disease in immature newborns. Emerging evidence indicates that GC exposure in early life may interfere with kidney function and is associated with hypertension in later life. In this study, we have investigated the effect of neonatal dexamethasone (DEX) administration on renal function i...

Inborn errors of mitochondrial beta-oxidation cause ectopic fat accumulation, particularly in the liver. Fatty liver is associated with insulin resistance and predisposes to hepatic fibrosis. The factors underlying the pathophysiological consequences of hepatic fat accumulation have remained poorly defined. Gene expression profiling in a model of a...

A key regulatory point in the control of fatty acid (FA) oxidation is thought to be transport of FAs across the mitochondrial membrane by carnitine palmitoyltransferase I (CPT I). To investigate the role of CPT I in FA metabolism, we used in vivo electrotransfer (IVE) to locally overexpress CPT I in muscle of rodents. A vector expressing the human...

Early exposure to glucocorticoids (GC) has been proposed to disturb hepatic and cardiac function in later life. In the present study, we evaluated early metabolic alterations upon GC treatment that may predispose to long-term abnormalities. Rats were injected with dexamethasone (DEX) at d 1, 2, and 3 after birth and controls received saline (SAL)....

Background: Glucocorticosteroids (mostly dexamethasone) are widely used to prevent chronic lung disease in premature infants. Neonatal rats treated with dexamethasone have been shown to have reduced cardiac mass and cardiomyocyte hypertrophy, suggesting a lower number of cardiomyocytes at adult age, and a severely reduced life expectancy. In the p...

Left ventricular (LV) pressure-volume relations provide relatively load-independent indexes of systolic and diastolic LV function, but few data are available on pressure-volume relations during growth and development in the normal adult heart. Furthermore, to quantify intrinsic ventricular function the indexes should be normalized for heart weight....

Glucocorticosteroid treatment is widely used to prevent chronic lung disease in premature infants. Recent studies in adult rats, treated with dexamethasone in the neonatal period, report negative long-term effects on the heart and severely reduced life expectancy. We treated neonatal rats with dexamethasone and studied cardiac function after 4 wk (...

Carnitine palmitoyltransferase I (CPT I) catalyzes the conversion of acyl-CoA to acylcarnitine at the outer mitochondrial membrane and is a key enzyme in the control of long-chain fatty acid (LC-FA) oxidation. Because myocardial LC-FA oxidation increases dramatically after birth, we determined the extent to which CPT I expression contributes to the...

Fatty acid and ketone body metabolism differ considerably between monogastric and ruminant species. The regulation of the key enzymes involved may differ accordingly. Carnitine palmitoyltransferase 1 (CPT 1) is the key locus for the control of long-chain fatty acid β-oxidation and liver ketogenesis. Previously we showed that CPT 1 kinetics in sheep...

Long-chain fatty acids (FA) coordinately induce the expression of a panel of genes involved in cellular FA metabolism in cardiac muscle cells, thereby promoting their own metabolism. These effects are likely to be mediated by peroxisome proliferator-activated receptors (PPARs). Whereas the significance of PPARalpha in FA-mediated expression has bee...

Glucocorticoid treatment in preterm babies to prevent chronic lung disease causes myocardial hypertrophy and increased myocardial protein content. Although these changes are thought to be transient, there is evidence that dexamethasone (DEX) induces permanent myocardial abnormalities as well. We investigated whether a therapeutic course of neonatal...

Malonyl-CoenzymeA acts as a fuel sensor, being both an intermediate of fatty acid synthesis and an inhibitor of the two known isoforms of carnitine palmitoyltransferase I (CPT I), which control mitochondrial fatty acid oxidation. We describe here a novel CPT1 family member whose mRNA is present predominantly in brain and testis. Chromosomal locatio...

Muscle-type carnitine palmitoyltransferase I (M-CPT I) is a key enzyme in the control of beta-oxidation of long-chain fatty acids in the heart and skeletal muscle. Because knowledge of the mammalian genes encoding M-CPT I may aid in studies of disturbed energy metabolism, we obtained new genomic and cDNA data for M-CPT I for the human, mouse, rat,...

Metabolic changes at around the time of birth are crucial for life. Here we review the energy utilization in the myocardium, emphasizing ketone body metabolism. Before birth, glucose and lactate are the major energy substrates for the myocardium. Long-chain fatty acids (LCFA) are normally not available as an energy substrate for the fetal heart; ho...

Carnitine (L-3-hydroxy-4-N-trimethylaminobutyric acid) forms esters with a wide range of acyl groups and functions to transport and excrete these groups. It is found in most cells at millimolar levels after uptake via the sodium-dependent carrier, OCTN2. The acylation state of the mobile carnitine pool is linked to that of the limited and compartme...

Five genes in the human genome are known to encode different active forms of related carnitine acyltransferases: CPT1A for liver-type carnitine palmitoyltransferase I, CPT1B for muscle-type carnitine palmitoyltransferase I, CPT2 for carnitine palmitoyltransferase II, CROT for carnitine octanoyltransferase, and CRAT for carnitine acetyltransferase....

Lactate accounts for a third of myocardial oxygen consumption before and in the first 2 weeks after birth. It is unknown how the remainder of myocardial oxygen is consumed. Glucose is thought to be important before birth, whereas long-chain fatty acids (LC-FA) are the prime substrate for the adult. However, the ability of the myocardium of the newb...

Carnitine palmitoyltransferase I (CPT I) is a key enzyme in the regulation of beta-oxidation. The topology of this enzyme has been difficult to elucidate by biochemical methods. We studied the topology of a fusion protein of muscle-type CPT I (M-CPT I) and green fluorescent protein (GFP) by microscopical means. To validate the use of the fusion pro...

Several severe congenital cardiomyopathies are known to be associated with deficiencies in long-chain fatty acid transport and oxidation. Our studies are focused on a key enzyme in the regulation of intracellular long-chain fatty acid transport: carnitine palmitoyltransferase 1. Of this enzyme, two isoforms are expressed in the neonatal heart: L-CP...

The generation and characterization of Pseudomonas putida KT2442 mutants affected in poly-3-hydroxyalkanoate (PHA) synthesis are reported. The mutants from P. putida KT2442 carrying several copies of the PHA-polymerase-encoding gene (phaC) were isolated via N-methyl-N′-nitro-N-nitrosoguanidine chemical mutagenesis and contained mutation(s) on genes...

We isolated and sequenced cDNA and genomic DNA fragments of the human CPT1B gene, encoding muscle type carnitine palmitoyltransferase I. A recombinant P1 phage containing CPT1B was mapped to chromosome 22qter by fluorescent in situ hybridization. This finding supports the concept that `liver type' and `muscle type' isoforms of CPT I are encoded by...

We isolated and sequenced cDNA and genomic DNA fragments of the human CPT1B gene, encoding muscle type carnitine palmitoyltransferase I. A recombinant P1 phage containing CPT1B was mapped to chromosome 22qter by fluorescent in situ hybridization. This finding supports the concept that `liver type' and `muscle type' isoforms of CPT I are encoded by...

We identified an open reading frame (ORF) which is located closely behind the gene encoding granule-bound starch synthase (GBSS) of potato (Solanum tuberosum L.). The ORF ends with a perfect 43 bp direct repeat, which carries the stop triplet precisely at the beginning of the second repeat. The deduced protein shows homology with all known isoforms...

Earlier described revertants, obtained after irradiation of an amylose-free (amf) mutant which carries a point deletion in the gene for granule-bound starch synthase, were analysed at the DNA-sequence level. Direct sequencing of fragments amplified by the polymerase chain reaction revealed that all investigated revertants carry the original wildtyp...

Agrobacterium rhizogenes-mediated introduction of the wild-type allele of the gene encoding granulebound starch synthase (GBSS) into the amylose-free starch mutantamf of potato leads to restoration of GBSS activity and amylose synthesis, which demonstrates thatAmf is the structural gene for GBSS. Amylose was found in columella cells of root tips, i...

The genomic sequence of the potato gene for starch granule-bound starch synthase (GBSS; waxy protein) has been determined for the wild-type allele of a monoploid genotype from which an amylose-free (amf) mutant was derived, and for the mutant part of the amf allele. Comparison of the wild-type sequence with a cDNA sequence from the literature and a...

The gene encoding granule-bound starch synthase (GBSS), which determines the presence of amylose in reserve starches, has been isolated from a wild-type and from an amylose-free potato by using a potato GBSS cDNA. From the analysis of five genomic GBSS clones, isolated from the wild-type potato, it is shown that GBSS is a single copy gene in potato...

An in situ hybridization procedure was developed for mitotic potato chromosomes by using a potato 24S rDNA probe. This repetitive sequence hybridized to the nucleolar organizer region (NOR) of chromosome 2 in 95%-100% of the metaphase plates. Another repetitive sequence (P5), isolated from the interdihaploid potato HH578, gave a "ladderpattern" in...

Bacterial enzymes are responsible for degradation of beta-aspartyl peptides in the intestinal tract. These peptides, especially the dipeptide beta-aspartylglycine, are useful as indicators of an impaired anaerobic intestinal microflora of antibiotic-treated patients. A method to separate the dipeptides beta-aspartylalanine, beta-aspartylglutamine,...

Agrobacterium rhizogenes-mediated introduction of the wild-type allele of the gene encoding granulebound starch synthase (GBSS) into the amylose-free starch mutantamf of potato leads to restoration of GBSS activity and amylose synthesis, which demonstrates that Amf is the structural gene for GBSS. Amylose was found in columella cells of root tips,...