Case Report: Carnitine Palmitoyl Transferase II (CPT II) Deficiency

Carnitine Palmitoyl Transferase II (CPTII) is a very important enzyme that helps with the oxidation of long-chain fatty acid to produce energy. Deficiency in CPTII will lead to energy deficiency in the case of fasting and the accumulation of the long chain fatty in the body. There are three types of CPT II deficiency, the myopathic form, the severe infantile hepatocardiomuscular form and the lethal neonatal form. They are all inherited as an autosomal recessive. Diagnosis of the CPTII are 1) tandem mass spectrometry (MS/MS) in adult form and 2) CPTII polymorphism (F352C), which is linked to reducing the activity of CPTII in infantile form [1]. Glucose is the primary management and medium-chain fatty acid is an alternative due to the bypass of the CPTII enzyme in the pathway. For the prevention of CPTII deficiency are to avoid long chain fatty acid (C12-fatty acid), fasting, prolonged exercise, known triggers, and certain medications such as anti-epileptics and general anesthesia. During the rhabdomyolysis and myoglobinuria attack, it is very important to maintain hydration to avoid acute renal failure. If, however, renal failure occurs, dialysis is recommended. We present a case of a 27-year-old African American woman with the significant past medical history of CPT II deficiency leading to recurrent rhabdomyolysis and myoglobinuria. Together with all the research studies from diagnosis to treatment of CPTII deficiency will help in clinical management of patients. And this case report will add to the existing case reports of patients who have CPTII deficiency in terms of how we diagnose, how we treat, and how we prevent symptoms from re-occurring.

Peroxisome proliferator-activated receptors as targets to treat non-alcoholic fatty liver disease

Lately, the world has faced tremendous progress in the understanding of non-alcoholic fatty liver disease(NAFLD) pathogenesis due to rising obesity rates. Peroxisome proliferator-activated receptors(PPARs) are transcription factors that modulate the expression of genes involved in lipid metabolism, energy homeostasis and inflammation, being altered in diet-induced obesity. Experimental evidences show that PPAR-alpha is the master regulator of hepatic beta-oxidation(mitochondrial and peroxisomal)and microsomal omega-oxidation, being markedly decreased by high-fat(HF) intake. PPAR-beta/delta is crucial to the regulation of forkhead box-containing protein O subfamily-1 expression and, hence, the modulation of enzymes that trigger hepatic gluconeogenesis. In addition, PPAR-beta/delta can activate hepatic stellate cells aiming to the hepatic recovery from chronic insult. On the contrary, PPAR-gamma upregulation by HF diets maximizes NAFLD through the induction of lipogenic factors, which are implicated in the fatty acid synthesis. Excessive dietary sugars also upregulate PPAR-gamma, triggering de novo lipogenesis and the consequent lipid droplets deposition within hepatocytes. Targeting PPARs to treat NAFLD seems a fruitful approach as PPAR-alpha agonist elicits expressive decrease in hepatic steatosis by increasing mitochondrial beta-oxidation, besides reduced lipogenesis. PPAR-beta/delta ameliorates hepatic insulin resistance by decreasing hepatic gluconeogenesis at postprandial stage. Total PPAR-gamma activation can exert noxious effects by stimulating hepatic lipogenesis. However, partial PPAR-gamma activation leads to benefits, mainly mediated by increased adiponectin expression and decreased insulin resistance. Further studies are necessary aiming at translational approaches useful to treat NAFLD in humans worldwide by targeting PPARs.

Role of Free Fatty Acids in Physiological Conditions and Mitochondrial Dysfunction

The role of free fatty acids (FFAs) as a source of energy and their functions in energy transport within the body are well established. Equally important is a role that FFAs play in oxidative stress following cell membrane depolarization. FFAs are physiologically active, not only as nutritional components, but also as molecules involved in cell signaling and stabilization of membranes via palmitoylation and myristoylation. Protein palmitoylation is involved in numerous cellular processes, including apoptosis, and neuronal transmission. Besides nuclear peroxisome proliferator-activated receptors that mediate the biological effects of FFAs, G protein-coupled receptors (GPCRs) that are activated by FFA, have been recently identified. Those multiple FFA receptors (FFARs), which function on the cell surface as activated FFAs, play significant roles in the regulation of energy metabolism and mediate a wide range of important metabolic processes. FFARs have been targeted in drug development for the treatment of type 2 diabetes and metabolic syndrome. FFAs upregulate transcription of uncoupling proteins, increasing their expression in brain, cardiac, and skeletal muscle that may be protective or cytotoxic, depending on the cellular energy state. Recently, FFA effects on the endothelial function and dysfunction are being recognized. FFAs play a key role in endothelium-dependent nitric oxide production. A disturbance of endothelial function, due to an imbalance in production and release of relaxing and constricting factors, has implications in the development of cardiovascular problems, such as hypertension, as well as neurotoxicity following loss of blood-brain barrier integrity. This review presents information on broad range of FFAs actions of prime importance for physiological processes. Understanding of FFA functions in the body is crucial for developing new therapeutic strategies against several metabolic disorders.

Crosstalk between mitochondria and peroxisomes

Mitochondria and peroxisomes are small ubiquitous organelles. They both play major roles in cell metabolism,especially in terms of fatty acid metabolism,reactive oxygen species(ROS) production,and ROS scavenging,and it is now clear that they metabolically interact with each other. These two organelles share some properties,such as great plasticity and high potency to adapt their form and number according to cell requirements. Their functions are connected,and any alteration in the function of mitochondria may induce changes inperoxisomal physiology. The objective of this paper was to highlight the interconnection and the crosstalk existing between mitochondria and peroxisomes. Special emphasis was placed on the best known connections between these organelles:origin,structure,and metabolic interconnections.

Chain Elongation Using Native Soil Inocula:Exceptional n-Caproate Biosynthesis Performance and Microbial Mechanisms

This study demonstrates the feasibility and effectiveness of utilizing native soils as a resource for inocula to produce n-caproate through the chain elongation(CE)platform,offering new insights into anaerobic soil processes.The results reveal that all five of the tested soil types exhibit CE activity when supplied with high concentrations of ethanol and acetate,highlighting the suitability of soil as an ideal source for n-caproate production.Compared with anaerobic sludge and pit mud,the native soil CE system exhibited higher selectivity(60.53%),specificity(82.32%),carbon distribution(60.00%),electron transfer efficiency(165.00%),and conductivity(0.59 ms∙cm^(-1)).Kinetic analysis further confirmed the superiority of soil in terms of a shorter lag time and higher yield.A microbial community analysis indicated a positive correlation between the relative abundances of Pseudomonas,Azotobacter,and Clostridium and n-caproate production.Moreover,metagenomics analysis revealed a higher abundance of functional genes in key microbial species,providing direct insights into the pathways involved in n-caproate formation,including in situ CO_(2)utilization,ethanol oxidation,fatty acid biosynthesis(FAB),and reverse beta-oxidation(RBO).The numerous functions in FAB and RBO are primarily associated with Pseudomonas,Clostridium,Rhodococcus,Stenotrophomonas,and Geobacter,suggesting that these genera may play roles that are involved or associated with the CE process.Overall,this innovative inoculation strategy offers an efficient microbial source for n-caproate production,underscoring the importance of considering CE activity in anaerobic soil microbial ecology and holding potential for significant economic and environmental benefits through soil consortia exploration.

Correlation between the different chain lengths of free fatty acid oxidation and abili .ty of trophoblastic invasion

Background Preeclampsia （PE） is associated with abnormal fatty acid beta-oxidation （FAO）, especially metabolic disorders of long-chain fatty acid oxidation. The role of FAO dysfunction in inadequate invasion is unclear. The aim of this study was to explore the influence of various lengths fatty acids oxidation on invasiveness of trophoblasts. Methods Primary human trophoblast cells and HTR8/SVneo cells were treated with fatty acids of various lengths. Morphological changes, lipid deposition and ultrastructure changes of trophoblast cells were detected. Cells invasiveness was determined by transwell insert. CPT1, CPT2 and long-chain 3-hydroxyacyI-CoA dehydrogenase （LCHAD） protein expression were analyzed. The correlation between intracellular lipid droplets deposition and cells invasiveness was evaluated. Results Cells treated with long-chain fatty acids showed significant increased lipid droplets deposition, severe mitochondrial damage, decreased CPT2 and LCHAD protein expression （P 〈0.05） but no significant difference in CPT1 protein expression （P 〉0.05）. Invasiveness of the trophoblast cells of the LC-FFA group significantly decreased （P 〈0.05）. Intracellular lipid droplets deposition was negatively correlated with invasivenss （R=-0.745, P 〈0.05）. Conclusion Trophoblast cells after stimulation with long chain fatty acids exist fatty acid oxidation disorders, and reduce the ability of trophoblastic invasion.

Unleashing the power of energy storage: Engineering β-oxidation pathways for polyketide production

Overproduction of polyketides has been a challenge for metabolic engineering for decades.However,recent studies have demonstrated that in both native host and heterologous host,engineeringβ-oxidation pathways can lead to dramatic improvement of polyketide production.