Bile acids facilitate the absorption of lipids in the gut, but are also needed to maintain cholesterol homeostasis, induce bile flow, excrete toxic substances and regulate energy metabolism by acting ...as signaling molecules. Bile acid biosynthesis is a complex process distributed across many cellular organelles and requires at least 17 enzymes in addition to different metabolite transport proteins to synthesize the two primary bile acids, cholic acid and chenodeoxycholic acid. Disorders of bile acid synthesis can present from the neonatal period to adulthood and have very diverse clinical symptoms ranging from cholestatic liver disease to neuropsychiatric symptoms and spastic paraplegias. This review describes the different bile acid synthesis pathways followed by a summary of the current knowledge on hereditary disorders of human bile acid biosynthesis with a special focus on diagnostic bile acid profiling using mass spectrometry.
Nanocellulose in green food packaging Vilarinho, Fernanda; Sanches Silva, Ana; Vaz, M Fátima ...
Critical reviews in food science and nutrition,
06/2018, Letnik:
58, Številka:
9
Journal Article
Recenzirano
The development of packaging materials with new functionalities and lower environmental impact is now an urgent need of our society. On one hand, the shelf-life extension of packaged products can be ...an answer to the exponential increase of worldwide demand for food. On the other hand, uncertainty of crude oil prices and reserves has imposed the necessity to find raw materials to replace oil-derived polymers. Additionally, consumers' awareness toward environmental issues increasingly pushes industries to look with renewed interest to "green" solutions. In response to these issues, numerous polymers have been exploited to develop biodegradable food packaging materials. Although the use of biopolymers has been limited due to their poor mechanical and barrier properties, these can be enhanced by adding reinforcing nanosized components to form nanocomposites. Cellulose is probably the most used and well-known renewable and sustainable raw material. The mechanical properties, reinforcing capabilities, abundance, low density, and biodegradability of nanosized cellulose make it an ideal candidate for polymer nanocomposites processing. Here we review the potential applications of cellulose based nanocomposites in food packaging materials, highlighting the several types of biopolymers with nanocellulose fillers that have been used to form bio-nanocomposite materials. The trends in nanocellulose packaging applications are also addressed.
Study of monogenic mitochondrial cardiomyopathies may yield insights into mitochondrial roles in cardiac development and disease. Here, we combined patient-derived and genetically engineered induced ...pluripotent stem cells (iPSCs) with tissue engineering to elucidate the pathophysiology underlying the cardiomyopathy of Barth syndrome (BTHS), a mitochondrial disorder caused by mutation of the gene encoding tafazzin (TAZ). Using BTHS iPSC-derived cardiomyocytes (iPSC-CMs), we defined metabolic, structural and functional abnormalities associated with TAZ mutation. BTHS iPSC-CMs assembled sparse and irregular sarcomeres, and engineered BTHS 'heart-on-chip' tissues contracted weakly. Gene replacement and genome editing demonstrated that TAZ mutation is necessary and sufficient for these phenotypes. Sarcomere assembly and myocardial contraction abnormalities occurred in the context of normal whole-cell ATP levels. Excess levels of reactive oxygen species mechanistically linked TAZ mutation to impaired cardiomyocyte function. Our study provides new insights into the pathogenesis of Barth syndrome, suggests new treatment strategies and advances iPSC-based in vitro modeling of cardiomyopathy.
Cardiolipin is a unique phospholipid, which is almost exclusively localized in the mitochondrial inner membrane where it is synthesized from phosphatidylglycerol and ...cytidinediphosphate-diacylglycerol. After primary synthesis, the mature acyl chain composition of cardiolipin is achieved by at least two remodeling mechanisms. In the mitochondrial membrane cardiolipin plays an important role in energy metabolism, mainly by providing stability for the individual enzymes and enzyme complexes involved in energy production. Moreover, cardiolipin is involved in different stages of the mitochondrial apoptotic process and in mitochondrial membrane dynamics. Cardiolipin alterations have been described in various pathological conditions. Patients suffering from Barth syndrome have an altered cardiolipin homeostasis caused by a primary deficiency in cardiolipin remodeling. Alterations in cardiolipin content or composition have also been reported in more frequent diseases such as diabetes and heart failure. In this review we provide an overview of cardiolipin metabolism, function and its role in different pathological states.
The enterohepatic circulation of bile salts is an important physiological route to recycle bile salts and ensure intestinal absorption of dietary lipids. The Na+‐taurocholate cotransporting ...polypeptide SLC10A1 (NTCP) plays a key role in this process as the major transporter of conjugated bile salts from the plasma compartment into the hepatocyte. Here we present the first patient with NTCP deficiency, who was clinically characterized by mild hypotonia, growth retardation, and delayed motor milestones. Total bile salts in plasma were extremely elevated (up to 1,500 μM, ref. <16.3) but there were no clinical signs of cholestatic jaundice, pruritis, or liver dysfunction. Bile salt synthesis and intestinal bile salt signaling were not affected, as evidenced by normal plasma 7α‐hydroxy‐4‐cholesten‐3‐one (C4) and FGF19 levels. Importantly, the presence of secondary bile salts in the circulation suggested residual enterohepatic cycling of bile salts. Sequencing of the SLC10A1 gene revealed a single homozygous nonsynonymous point mutation in the coding sequence of the gene, resulting in an arginine to histidine substitution at position 252. Functional studies showed that this mutation resulted in a markedly reduced uptake activity of taurocholic acid. Immunofluorescence studies and surface biotinylation experiments demonstrated that the mutant protein is virtually absent from the plasma membrane. Conclusion: We describe the identification of NTCP deficiency as a new inborn error of metabolism with a relatively mild clinical phenotype. The identification of NTCP deficiency confirms that this transporter is the main import system for conjugated bile salts into the liver but also indicates that auxiliary transporters are able to sustain the enterohepatic cycle in its absence. (Hepatology 2015;61:260–267)
X-linked adrenoleukodystrophy (ALD), a progressive neurodegenerative disease, is caused by mutations in ABCD1 and characterized by very-long-chain fatty acids (VLCFA) accumulation. Virtually all ...males develop progressive myelopathy (AMN). A subset of patients, however, develops a fatal cerebral demyelinating disease (cerebral ALD). Hematopoietic stem cell transplantation is curative for cerebral ALD provided the procedure is performed in an early stage of the disease. Unfortunately, this narrow therapeutic window is often missed. Therefore, an increasing number of newborn screening programs are including ALD. To identify new biomarkers for ALD, we developed an Abcd1 knockout mouse with enhanced VLCFA synthesis either ubiquitous or restricted to oligodendrocytes. Biochemical analysis revealed VLCFA accumulation in different lipid classes and acylcarnitines. Both C26:0-lysoPC and C26:0-carnitine were highly elevated in brain, spinal cord, but also in bloodspots. We extended the analysis to patients and confirmed that C26:0-carnitine is also elevated in bloodspots from ALD patients. We anticipate that validation of C26:0-carnitine for the diagnosis of ALD in newborn bloodspots may lead to a faster inclusion of ALD in newborn screening programs in countries that already screen for other inborn errors of metabolism.
• Background The Lathyrus genus includes 160 species, some of which have economic importance as food, fodder and ornamental crops (mainly L. sativus, L. cicera and L. odoratus, respectively) and are ...cultivated in > 1·5 Mha worldwide. However, in spite of their well-recognized robustness and potential as a source of calories and protein for populations in drought-prone and marginal areas, cultivation is in decline and there is a high risk of genetic erosion. • Scope In this review, current and past taxonomic treatments of the Lathyrus genus are assessed and its current status is examined together with future prospects for germplasm conservation, characterization and utilization. A particular emphasis is placed on the importance of diversity analysis for breeding of L. sativus and L. cicera. • Conclusions Efforts for improvement of L. sativus and L. cicera should concentrate on the development of publicly available joint core collections, and on high-resolution genotyping. This will be critical for permitting decentralized phenotyping. Such a co-ordinated international effort should result in more efficient and faster breeding approaches, which are particularly needed for these neglected, underutilized Lathyrus species.
ABSTRACT
Peroxisomes are essential organelles for the specialized oxidation of a wide variety of fatty acids, but they are also able to degrade fatty acids that are typically handled by mitochondria. ...Using a combination of pharmacological inhibition and clustered regularly interspaced short palindromic repeats (CRISPR)‐CRISPR associated protein 9 genome editing technology to simultaneously manipulate peroxisomal and mitochondrial fatty acid β‐oxidation (FAO) in HEK‐293 cells, we identified essential players in the metabolic crosstalk between these organelles. Depletion of carnitine palmitoyltransferase (CPT)2 activity through pharmacological inhibition or knockout (KO) uncovered a significant residual peroxisomal oxidation of lauric and palmitic acid, leading to the production of peroxisomal acylcarnitine intermediates. Generation and analysis of additional single‐ and double‐KO cell lines revealed that the D‐bifunctional protein (HSD17B4) and the peroxisomal ABC transporter ABCD3 are essential in peroxisomal oxidation of lauric and palmitic acid. Our results indicate that peroxisomes not only accept acyl‐CoAs but can also oxidize acylcarnitines in a similar biochemical pathway. By using an Hsd17b4 KO mouse model, we demonstrated that peroxisomes contribute to the plasma acylcarnitine profile after acute inhibition of CPT2, proving in vivo relevance of this pathway. We summarize that peroxisomal FAO is important when mitochondrial FAO is defective or overloaded.—Violante, S., Achetib, N., van Roermund, C. W. T., Hagen, J., Dodatko, T., Vaz, F. M., Waterham, H. R., Chen, H., Baes, M., Yu, C., Argmann, C. A., Houten, S. M. Peroxisomes can oxidize medium‐ and long‐chain fatty acids through a pathway involving ABCD3 and HSD17B4. FASEB J. 33, 4355–4364 (2019). www.fasebj.org
Activation of brown adipose tissue (BAT) contributes to total body energy expenditure through energy dissipation as heat. Activated BAT increases the clearance of lipids and glucose from the ...circulation, but how BAT accommodates large influx of multiple substrates is not well defined. The purpose of this work was to assess the metabolic fluxes in brown adipocytes during β3-adrenergic receptor (β3-AR) activation.T37i murine preadipocytes were differentiated into brown adipocytes and we used Seahorse respirometry employing a set of specific substrate inhibitors in the presence or absence of β3-AR agonist CL316,243. The main substrate used by these brown adipocytes were fatty acids, which were oxidized equally during activation as well as during resting condition. U-
C-glucose tracer-based metabolomics revealed that the flux through the TCA cycle was enhanced and regulated by pyruvate dehydrogenase (PDH) activity. Based on
C-tracer incorporation in lipids, it appeared that most glucose was oxidized via TCA cycle activity, while some was utilized for glycerol-3-phosphate synthesis to replenish the triglyceride pool. Collectively, we show that while fatty acids are the main substrates for oxidation, glucose is also oxidized to meet the increased energy demand during short term β3-AR activation. PDH plays an important role in directing glucose carbons towards oxidation.
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