Carnitine Palmitoyltransferase Research Articles

Evaluation of free and bound carnitine in young athletes

The study of the characteristics of carnitine metabolism in representatives of certain sports makes it possible to study the effect of physical loads of various nature on the body of a young athlete, and also makes it possible to assess the competitive potential and predict the tolerance of long-term and intense loads. Purpose. This study is to investigate the characteristics of carnitine metabolism in young athletes of various specializations. Material and methods. The study included athletes aged 14 to 18 who had been engaged in intense physical exercise for at least 12 hours per week forthe past 12 months or more. The control group consisted of healthy children aged 14 to 18 who were not involved in sports. In the blood serum of all study participants, the concentration of free carnitine, acetylcarnitine and acylcarnitines was determined. Based on the data obtained, ratios were calculated reflecting the activity of lipid beta-oxidation enzymes. Results. We found that the content of free carnitine in the representatives of all the studied groups was within the normal range. At the same time, the level of free carnitine in the blood of athletes involved in field hockey was significantly lower than that of athletes-swimmers and representatives of the control group (p<0.001). It was also studied that, compared with athletes-swimmers and the control group, athletes-hockey players have significantly higher functional activity of carnitine palmitoyltransferase 1 (p<0.05) and lipid beta-oxidation enzymes (p<0.001). Conclusion. In our work we have demonstrated that athletes involved in team sports (field hockey) have a more pronounced shift towards fatty acid oxidation compared to aerobic sports (swimming). A possible reason for the identified changes may be a more significant effect of alternating aerobic and anaerobic loads on lipid metabolism compared to exclusively aerobic activity.

Esculeogenin A, a Glycan from Tomato, Alleviates Nonalcoholic Fatty Liver Disease in Rats through Hypolipidemic, Antioxidant, and Anti-Inflammatory Effects.

This study examined the preventative effects of esculeogenin A (ESGA), a newly discovered glycan from tomato, on liver damage and hepatic steatosis in high-fat-diet (HFD)-fed male rats. The animals were divided into six groups (each of eight rats): a control group fed a normal diet, control + ESGA (200 mg/kg), HFD, and HFD + ESAG in 3 doses (50, 100, and 200 mg/kg). Feeding and treatments were conducted for 12 weeks. Treatment with ESGA did not affect gains in the body or fat weight nor increases in fasting glucose, insulin, and HOMA-IR or serum levels of free fatty acids (FFAs), tumor-necrosis factor-α, and interleukin-6 (IL-6). On the contrary, it significantly reduced the serum levels of gamma-glutamyl transpeptidase (GGT), aspartate aminotransferase (AST), alanine aminotransferase (ALT), total triglycerides (TGs), cholesterol (CHOL), and low-density lipoprotein cholesterol (LDL-c) in the HFD-fed rats. In addition, it improved the liver structure, attenuating the increase in fat vacuoles; reduced levels of TGs and CHOL, and the mRNA levels of SREBP1 and acetyl CoA carboxylase (ACC); and upregulated the mRNA levels of proliferator-activated receptor α (PPARα) and carnitine palmitoyltransferase I (CPT I) in HFD-fed rats. These effects were concomitant with increases in the mRNA, cytoplasmic, and nuclear levels of nuclear factor erythroid 2-related factor 2 (Nrf2), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and heme oxygenase-1 (HO); a reduction in the nuclear activity of nuclear factor-kappa beta (NF-κB); and inhibition of the activity of nuclear factor kappa B kinase subunit beta (IKKβ). All of these effects were dose-dependent effects in which a normal liver structure and normal levels of all measured parameters were seen in HFD + ESGA (200 mg/kg)-treated rats. In conclusion, ESGA prevents NAFLD in HFD-fed rats by attenuating hyperlipidemia, hepatic steatosis, oxidative stress, and inflammation by acting locally on Nrf2, NF-κB, SREBP1, and PPARα transcription factors.

A novel CPT1A covalent inhibitor modulates fatty acid oxidation and CPT1A-VDAC1 axis with therapeutic potential for colorectal cancer

Colorectal cancer (CRC) is a common and deadly disease of the digestive system, but its targeted therapy is hampered by the lack of reliable and specific biomarkers. Hence, discovering new therapeutic targets and agents for CRC is an urgent and challenging task. Here we report that carnitine palmitoyltransferase 1A (CPT1A), a mitochondrial enzyme that catalyzes fatty acid oxidation (FAO), is a potential target for CRC treatment. We show that CPT1A is overexpressed in CRC cells and that its inhibition by a secolignan-type compound, 2,6-dihydroxypeperomin B (DHP-B), isolated from the plant Peperomia dindygulensis, suppresses tumor cell growth and induces apoptosis. We demonstrate that DHP-B covalently binds to Cys96 of CPT1A, blocks FAO, and disrupts the mitochondrial CPT1A-VDAC1 interaction, leading to increased mitochondrial permeability and reduced oxygen consumption and energy metabolism in CRC cells. We also reveal that CPT1A expression correlates with the survival of tumor-bearing animals and that DHP-B exhibits anti-CRC activity in vitro and in vivo. Our study uncovers the molecular mechanism of DHP-B as a novel CPT1A inhibitor and provides a rationale for its preclinical development as well as a new strategy for CRC targeted therapy.

Experience with carnitine palmitoyltransferase II deficiency: diagnostic challenges in the myopathic form.

Carnitine palmitoyltransferase II (CPT II) deficiency is an autosomal recessive disorder of long-chain fatty acid oxidation. Three clinical phenotypes, lethal neonatal form, severe infantile hepatocardiomuscular form, and myopathic form, have been described in CPT II deficiency. The myopathic form is usually mild and can manifest from infancy to adulthood, characterised by recurrent rhabdomyolysis episodes. The study aimed to investigate the clinical features, biochemical, histopathological, and genetic findings of 13 patients diagnosed with the myopathic form ofCPT II deficiency at Ege University Hospital. A retrospective study was conducted with 13 patients with the myopathic form of CPT II deficiency. Our study considered demographic data, triggers of recurrent rhabdomyolysis attacks, biochemical metabolic screening, and molecular analysis. Ten patients were examined for rhabdomyolysis ofunknown causes. Two patients were diagnosed during family screening, and one was diagnosed during investigations due to increased liver function tests. Acylcarnitine profiles were normal in five patients during rhabdomyolysis. Genetic studies have identified a c.338C>T (p.Ser113Leu) variant homozygous in 10 patients. One patient showed a novel frameshift variant compound heterozygous with c.338C>T (p.Ser113Leu). Plasma acylcarnitine analysis should be preferred as it is superior to DBS acylcarnitine analysis in diagnosing CPT II deficiency. Even if plasma acylcarnitine analysis is impossible, CPT2 gene analysis should be performed. Our study emphasizes that CPT II deficiency should be considered in the differential diagnosis of recurrent rhabdomyolysis, even if typical acylcarnitine elevation does not accompany it.

PSI-11 Phyllanthus Urinaria Water Extract Ameliorates Lipid Accumulation and Oxidative Stress in Primary Chicken Hepatocytes

Abstract Fatty liver syndrome is a common metabolic disease that causes decrease in egg production and sudden death of laying hens. Phyllanthus urinaria (PU), a traditional herbal medicine, is widely used as anti-inflammatory and hepatoprotective medicine in Asia. The aim of this study was to investigate the effect of PU water extract on lipid accumulation and oxidative stress in an in vitro fatty liver syndrome model. Primary hepatocytes were isolated from 18 days of Lohmann embryonic chicks. Hepatocytes were cultured in medium with oleic acid (OA, 500 μM) or palmitic acid (PA, 200 μM) to induce lipid accumulation and oxidative stress respectively. Both experiments were treated with different concentration of PU water extract (0, 2, 10, 50 μg/mL) for 24 h. Metformin hydrochloride (1 mM) was used as a positive control. Cell viability, total triglycerides, TBARS, Oil red O staining, and mRNA expression of lipid metabolism-related genes were determined. The results indicated that PU water extract significantly decreased total triglycerides level (P < 0.05) in OA induced lipid accumulation. Moreover, treatment of PU water extract could down-regulate the mRNA abundance of sterol regulatory element-binding protein 1 (SREBP1c), up-regulate the mRNA expression of carnitine palmitoyltransferase 1A (CPT1A) and peroxisome proliferator-activated receptor alpha (PPARα) in lipid accumulated hepatocytes. In oxidative stress experiment, PU water extract at the doses above 10 μg/mL of attenuated increase of malondialdehyde (MDA) abundance induced by PA (P < 0.05). We speculated that PU water extract effectively ameliorate lipid accumulation in primary chicken hepatocytes through decreasing of lipogenesis and increasing of beta-oxidation. PU water extract reduced lipid peroxidase, showing antioxidant effects. These results provide preliminary evidence for supporting PU water extract as a potential therapeutic agent to prevent and treat fatty liver syndrome in chickens.

Unsaponifiable Matter from Wheat Bran Cultivated in Korea Inhibits Hepatic Lipogenesis by Activating AMPK Pathway.

Unsaponifiable matter (USM) from wheat bran, a by-product obtained from wheat milling, is abundant in health-promoting compounds such as phytosterols, tocopherols, policosanols, and alkylresorcinols. This study aimed to examine the effects of USM from the wheat bran of normal and waxy type wheat, Saekeumkang (SKK) and Shinmichal (SMC), on hepatic lipid accumulation in free fatty acid (FFA)-induced hepatocytes and to investigate the cellular mechanism. The total phytochemical contents were 46.562 g/100 g USM and 38.130 g/100 g USM from SKK and SMC, respectively. FFA treatment increased intracellular lipid accumulation by approximately 260% compared to the control group; however, treatment with USM from SKK and SMC significantly attenuated lipid accumulation in the hepatocytes in a dose-dependent manner. Moreover, USM downregulated the expression of lipogenic factors such as fatty acid synthase and sterol regulatory-element-binding protein 1c by approximately 40% compared to the FFA treatment group. Treatment with USM promoted lipolysis and positively regulated the expression of the proteins involved in β-oxidation, including peroxisome proliferator-activated receptor α and its downstream protein, carnitine palmitoyltransferase 1A. Moreover, the blockade of AMPK activation significantly abolished the inhibitory effects of USM on hepatic lipid accumulation. These results indicated that the USM from both SKK and SMC can alleviate lipid accumulation in hepatocytes in an AMPK-dependent manner. Therefore, USM from wheat bran may be useful as a therapeutic intervention for treating metabolic-dysfunction-associated fatty liver disease.

Senescent Endothelial Cells Sustain Their Senescence-Associated Secretory Phenotype (SASP) through Enhanced Fatty Acid Oxidation.

Cellular senescence is closely linked to endothelial dysfunction, a key factor in age-related vascular diseases. Senescent endothelial cells exhibit a proinflammatory phenotype known as SASP, leading to chronic inflammation (inflammaging) and vascular impairments. Albeit in a state of permanent growth arrest, senescent cells paradoxically display a high metabolic activity. The relationship between metabolism and inflammation is complex and varies across cell types and senescence inductions. While some cell types shift towards glycolysis during senescence, others favor oxidative phosphorylation (OXPHOS). Despite the high availability of oxygen, quiescent endothelial cells (ECs) tend to rely on glycolysis for their bioenergetic needs. However, there are limited data on the metabolic behavior of senescent ECs. Here, we characterized the metabolic profiles of young and senescent human umbilical vein endothelial cells (HUVECs) to establish a possible link between the metabolic status and the proinflammatory phenotype of senescent ECs. Senescent ECs internalize a smaller amount of glucose, have a lower glycolytic rate, and produce/release less lactate than younger cells. On the other hand, an increased fatty acid oxidation activity was observed in senescent HUVECs, together with a greater intracellular content of ATP. Interestingly, blockade of glycolysis with 2-deoxy-D-glucose in young cells resulted in enhanced production of proinflammatory cytokines, while the inhibition of carnitine palmitoyltransferase 1 (CPT1), a key rate-limiting enzyme of fatty acid oxidation, ameliorated the SASP in senescent ECs. In summary, metabolic changes in senescent ECs are complex, and this research seeks to uncover potential strategies for modulating these metabolic pathways to influence the SASP.

CPT1a Controls the Function of Long-Term Hematopoietic Stem Cells By Regulating the Balance between Fatty Acid Oxidation and Oxphos in Mitochondria

Hematopoietic stem cells (HSCs) rely on the balance in place of quiescence and self-renewal to sustain stem cell potential and differentiation to generate mature blood cells. Appropriate regulation of cellular and mitochondrial metabolic processes such as glycolysis, OXPHOS, fatty acid metabolism, and amino acid metabolism are required for HSC maintenance. However, the mechanisms by which cellular and mitochondrial metabolisms regulate HSC quiescence, proliferation, and differentiation remain to be fully understood. Fatty acid oxidation (FAO) is a metabolic process involving the breakdown of fatty acids into acetyl-CoA, which is then transported into mitochondria by carnitine palmitoyltransferase 1a (CPT1a). It has been reported that inhibiting FAO using non-specific inhibitors of CPT1a impairs HSC maintenance. Interestingly, CPT1a forms a complex with the Fanconi anemia complementation group D2 (FANCD2) protein (T Zhang et al., Scientific Reports, 2017). Given that Fanconi anemia is associated with HSC defects, this CPT1a complex may play a critical role in maintaining fatty acid dependent mitochondrial metabolism that mediates HSC dormancy and stemness. However, the exact role, in HSCs, of mitochondrial CPT1a, the rate-limiting enzyme in FAO, remains unknown. Here, we find that CPT1a is highly enriched in hematopoietic stem cells. Further, we investigated the role of CPT1a in hematopoiesis utilizing a CPT1aconditional knockout in mice driven by Vav1-Cre. The CPT1a knockout ( Cpt1aΔ/Δ) displays profound HSC defects, including loss of HSC self-renewal and accelerated differentiation. Mechanistically, we find that loss of Cpt1a results in increased ATP production, mitochondrial membrane potential (Δφm), and mitochondrial ROS accumulation in long-term HSCs (LT-HSCs), as well as defective LT-HSC function indicated by bone marrow transplantation and 5-FU genotoxic stress assays. Furthermore, utilizing mitochondrial complex formation assays and measurements of mitochondrial complex activity, BM cells of Cpt1aΔ/Δ mice display enhanced mitochondrial complex formation and up-regulation of mitochondrial complex activity. Our results suggest that Cpt1a regulates FAO transport and that loss of Cpt1a deregulates mitochondrial metabolisms including oxidative phosphorylation (OXPHOS). Taken together, our study suggests that CPT1a plays a key role in LT-HSC maintenance by controlling the balance between FAO and OXPHOS in mitochondria. Because of the noncanonical relationship between CPT1a and FANCD2 for the regulation of mitochondrial metabolism, correction of fatty acid metabolism and OXPHOS may present a novel therapeutic avenue for Fanconi anemia.

Biochanin-A attenuates high-fat diet and streptozotocin-induced hyperlipidemia and oxidative stress in rats by improving antioxidant status and lipid metabolic markers

Objective: To determine how biochanin-A (BCA) affects high-fat diet and streptozotocin-induced pathological changes in lipid metabolism and antioxidant status in diabetic rats. Methods: Diabetic rats were orally administered BCA (10 mg/kg body weight) for 30 days to investigate its effects on lipid profiles and oxidative stress markers in the liver and kidney. In addition, the mRNA expression of antioxidant and lipid metabolism enzymes in the liver was examined. Results: BCA attenuated hyperlipidemia by regulating mRNA expressions of HMG-CoA reductase, fatty acid synthase, carnitine palmitoyl transferase, and acetyl-CoA carboxylase. Additionally, BCA reduced high-fat diet and streptozotocin-induced oxidative stress by suppressing lipid peroxidation, improving superoxide dismutase, catalase, and glutathione peroxidase levels, and upregulating mRNA expressions of these enzymes. Conclusions: BCA may be a promising nutraceutical for the treatment of dyslipidemia and oxidative stress associated with diabetes.

The role of mitochondria in the pathogenesis of sarcopenia: a concise review

The aging process results in progressive loss of muscle mass and strength, a condition known as sarcopenia. At biological-molecular level, this condition is characterized by numerous changes that occur in the muscle cell, such as increased protein degradation, apoptosis, altered autophagy process, impaired myogenic pathway, and mitochondrial dysfunction. The purpose of this concise review is to provide a brief overview of the involvement of mitochondria in the pathogenesis of sarcopenia, highlighting the potential involvement of carnitine palmitoyl transferase 1, an enzyme localized in the outer mitochondrial membrane, involved in the transport of long-chain fatty acids into the mitochondrion for β-oxidation. This protein is a potential new player in the pathogenesis of sarcopenia, since it may be responsible for the accumulation of fat mass and the development of insulin resistance in the muscle tissue of affected subjects, thus suggesting a new pathway underlying the onset and progression of the disease. KEY WORDS: Sarcopenia, mitochondria, muscle, mitochondrial dysfunction, energy metabolism.

Newborn Screening with (C16 + C18:1)/C2 and C14/C3 for Carnitine Palmitoyltransferase II Deficiency throughout Japan Has Revealed C12/C0 as an Index of Higher Sensitivity and Specificity.

Carnitine palmitoyltransferase (CPT) II deficiency is a long-chain fatty acid oxidation disorder. It manifests as (1) a lethal neonatal form, (2) a hypoglycemic form, or (3) a myopathic form. The second form can cause sudden infant death and is more common among Japanese people than in other ethnic groups. Our study group had earlier used (C16 + C18:1)/C2 to conduct a pilot newborn screening (NBS) study, and found that the use of C14/C3 for screening yielded lower rates of false positivity; in 2018, as a result, nationwide NBS for CPT II deficiency started. In this study, we evaluated the utility of these ratios in 71 NBS-positive infants and found that the levels of both C14/C3 and (C16 + C18:1)/C2 in patients overlapped greatly with those of infants without the disease. Among the levels of acylcarnitines with various chain lengths (C18 to C2) and levels of free carnitine (C0) as well as their ratios of various patterns, C12/C0 appeared to be a promising index that could reduce false-positive results without missing true-positive cases detected by current indices. Although some cases of the myopathic form may go undetected even with C12/C0, its use will help prevent life-threatening onset of the hypoglycemic form of CPT II deficiency.

An hypothesis on crustacean pigmentation metabolism: l-carnitine and nuclear hormone receptors as limiting factors

Abstract Astaxanthin (Axn) is the primary pigment molecule in crustaceans associated with quality, health and growth traits, leading to increased marketing value. Axn can be contained within the protein complex crustacyanin (CRCN) to produce an array of different shell colours, or esterified with fatty acids (FA) for storage but also contributing additional red colouration. l-Carnitine (LC) has a major role in FA oxidation and mitochondrial function optimization, which could influence the proportion of Axn complexed with FA or CRCN. Peroxisome proliferator activated receptors (PPARs) have important roles in FA and Axn uptake, and stored lipid oxidation affecting Axn homeostasis and storage in lipid bodies. Whether Axn could increase PPAR signalling and carnitine palmitoyl transferase activity, leading to induction of lipid metabolism, is not known in crustaceans. Several FA have been shown to preferentially form FA Axn-esters, including saturated fatty acids (SFA) such as C16:0 and C18:0, mono-unsaturated fatty acids (MUFA) such as C16:1 and C18:1, and poly-unsaturated fatty acids (PUFA) such as C20:4, C20:5, and C20:6. We hypothesize that manipulating the dietary ratios and inclusion of LC, Axn, and specific FA may be able to further improve pigment utilization, lipid metabolism, health, and growth in crustaceans.

Hepatic metabolism of grazing cows of two Holstein strains under two feeding strategies with different levels of pasture inclusion.

The objective of the study was to characterize adaptations of hepatic metabolism of dairy cows of two Holstein strains with varying proportions of grazing in the feeding strategy. Multiparous autumn calving Holstein cows of New Zealand (NZH) and North American (NAH) strains were assigned to a randomized complete block design with a 2 x 2 factorial arrangement with two feeding strategies that varied in the proportions of pasture and supplementation: maximum pasture and supplementation with a pelleted concentrate (MaxP) or fixed pasture and supplementation with a total mixed ration (FixP) from May through November of 2018. Hepatic biopsies were taken at - 45 ± 17, 21 ± 7, 100 ± 23 and 180 ± 23 days in milk (DIM), representing prepartum, early lactation, early mid-lactation and late mid-lactation. The effects of DIM, feeding strategy (FS), strain and their interactions were analyzed with mixed models using repeated measures. Cows of both strains had similar triglyceride levels, mitochondrial function and carnitine palmitoyltransferase activity in liver during lactation. However, there was an effect of DIM and FS as liver triglyceride was higher for the MaxP strategy at 21 DIM and both mitochondrial function and carnitine palmitoyltransferase activity in liver were lower for the MaxP strategy at 21 DIM. Hepatic mitochondrial function and acetylation levels were affected by the interaction between strain and feeding strategy as both variables were higher for NAH cows in the MaxP strategy. Mid-lactation hepatic gene expression of enzymes related to fatty acid metabolism and nuclear receptors was higher for NZH than NAH cows. This work confirms the association between liver triglyceride, decreased hepatic mitochondrial function and greater mitochondrial acetylation levels in cows with a higher inclusion of pasture and suggests differential adaptative mechanisms between NAH and NZH cows to strategies with varying proportions of grazing in the feeding strategy.

Effects of Exercise Training on Mitochondrial Fatty Acid β-Oxidation in the Kidneys of Dahl Salt-Sensitive Rats

Exercise training (Ex) has anti-hypertensive and renal protective effects. In this study, we investigate the effects of Ex on mitochondrial fatty acid metabolism in the kidneys of Dahl salt-sensitive (Dahl-S) rats fed a high-salt (HS) diet. Eight-week-old, male Dahl-S rats were divided into three groups: (1) normal-salt diet, sedentary (NS-Sed), (2) HS diet, sedentary (HS-Sed), and (3) HS-Ex. The NS and HS groups were fed a diet containing 0.6% and 8% NaCl, respectively. The HS-Ex group performed treadmill running for 8 weeks (5 days/week; 60 min/day at 16–20 m/min, 0% gradient). Renal function and the expression of enzymes and regulators of β-oxidation and electron transport chain (ETC) complexes were assessed. HS increased systolic blood pressure and proteinuria, and Ex ameliorated these defects. HS also reduced creatinine clearance, and Ex ameliorated it. HS reduced the renal expression of enzymes of β-oxidation (carnitine palmitoyltransferase type I (CPTI) and acyl-CoA dehydrogenases (CADs)) and the related transcription factors peroxisome proliferator-activated receptor α (PPARα) and PPARγ-coactivator-1α (PGC-1α), and Ex restored this. HS also reduced the renal expression of enzymes in ETC complexes, and Ex restored this expression. Ex ameliorates HS-induced renal damage by upregulating enzymes involved in fatty acid β-oxidation and ETC complexes via increases in PPAR-α and PGC-1α expressions in the kidneys of Dahl-S rats. These results suggest that Ex may have beneficial effects on HS-induced mitochondrial dysfunction in the kidney.

The effect of lipid metabolism disorder on patients with hyperuricemia using Multi-Omics analysis

A multiomics study was conducted to investigate how lipid metabolism disorders affect the immune system in Xinjiang patients with hyperuricemia. The serum of 60 healthy individuals and 60 patients with hyperuricemia was collected. This study used LC–MS and HPLC to analyze differential lipid metabolites and enrichment pathways. It measured levels of immune factors tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), carnitine palmitoyltransferase-1 (CPT1), transforming growth factor-β1 (TGF-β1), glucose (Glu), lactic acid (LD), interleukin 10 (IL-10), and selenoprotein 1 (SEP1) using ELISA, as well as to confirm dysregulation of lipid metabolism in hyperuricemia. 33 differential lipid metabolites were significantly upregulated in patients with hyperuricemia. These lipid metabolites were involved in arachidonic acid metabolism, glycerophospholipid metabolism, linoleic acid metabolism, glycosylphosphatidylinositol (GPI)—anchor biosynthesis, and alpha-Linolenic acid metabolism pathways. Moreover, IL-10, CPT1, IL-6, SEP1, TGF-β1, Glu, TNF-α, and LD were associated with glycerophospholipid metabolism. In patients with hyperuricemia of Han and Uyghur nationalities, along with healthy individuals, significant differences in CPT1, TGF-β1, Glu, and LD were demonstrated by ELISA (P < 0.05). Furthermore, the levels of SEP1, IL-6, TGF-β1, Glu, and LD differed considerably between groups of the same ethnicity (P < 0.05). It was found that 33 kinds of lipid metabolites were significantly different in patients with hyperuricemia, which mainly involved 5 metabolic pathways. According to the results of further studies, it is speculated that CPT1, TGF-β1, SEP1, IL-6, Glu and LD may increase fatty acid oxidation and mitochondrial oxidative phosphorylation in patients through glycerophospholipid pathway, reduce the rate of glycolysis, and other pathways to change metabolic patterns, promote different cellular functions, and thus affect the disease progression in patients with hyperuricemia.

Glycerol monolaurate improves growth, lipid utilization and antioxidative status of white-leg shrimp, Penaeus vannamei fed with varying protein-lipid diets reared in inland saline water

Higher lipid at suboptimum dietary protein level can be a suitable approach to formulate cost-effective feed for cultured fish. However, excess lipid may cause metabolic burden to animals resulted in growth retardation with lipid deposition. Therefore, a feeding trial of 60 days was conducted to assess the effect of glycerol monolaurate (GML) supplemented in varying protein and lipid diets on growth, lipid utilization, antioxidant status and biochemical indices of white-leg shrimp, Penaeus vannamei juveniles reared in inland saline water (ISW). Accordingly, three hetero-lipidic (5–9% lipid), hetero-nitrogenous (30–36% CP), and hetero-energetic (379–400 Kcal DE/100 g) diets with three levels of GML (0%, 0.07% and 0.1%) were formulated for nine diets viz. P36L5G0 (36% CP, 5% lipid and 0% GML), P36L5G0.07 (36% CP, 5% lipid and 0.07% GML), P36L5G0.1 (36% CP, 5% lipid and 0.1% GML), P33L7G0 (33% CP, 7% lipid and 0% GML), P33L7G0.07 (33% CP, 7% lipid and 0.07% GML), P33L7G0.1 (33% CP, 7% lipid and 0.1% GML), P30L9G0 (30% CP, 9% lipid and 0% GML), P30L9G0.07 (30% CP, 9% lipid and 0.07% GML) and P30L9G0.1 (30% CP, 9% lipid and 0.1% GML). Five hundred and forty P. vannamei juveniles (4.02 ± 0.01 g) were randomly distributed following 3 × 3 factorial design. Highest (p < 0.05) weight gain. Specific growth rate, protein efficiency ratio, lipid efficiency ratio, whole body protein with lowest feed conversion ratio, whole body lipid, and hepatopancreas–somatic index was recorded in P33L7G0.1 group. Hepatopancreatic amylase and lipase activities increased (p < 0.05) significantly while protease activity decreased in relation to increased levels of dietary lipid. However, supplementing GML resulted in increased (p < 0.05) activity of all digestive enzymes and highest activity was found in 0.1% GML fed group. Lipid metabolic enzyme glucose-6-phosphate dehydrogenase and carnitine palmitoyltransferase-1 activities were found maximum (p < 0.05) in P33L7G0.1 group and lowest in P36L5G0 group. Hepatopancreatic and branchial superoxide dismutase and catalase activities showed a decreased (p < 0.05) and increased trend with dietary lipid levels, while GML reduced the activities and lowest activity recorded in P33L7G0.1 group. Shrimps of 9% lipid group exhibited highest serum malondialdehyde, glucose, cholesterol and triglyceride levels but 0.1% GML significantly showed the lowest levels that other groups. Higher hemocyanin and total protein observed in 33% dietary protein and 0.1% GML fed group. Therefore, 33% protein, 7% lipid with 0.1% GML is optimum for maximum growth performance, lipid utilization, whole body protein, and antioxidative status of white-leg shrimp, P. vannamei juveniles reared in ISW of 10 ppt.

The CPT1A Arctic variant: perspectives of community members and providers in two Alaska tribal health settings.

Newborn screening in Alaska includes screening for carnitine palmitoyltransferase 1A (CPT1A) deficiency. The CPT1A Arctic variant is a variant highly prevalent among Indigenous peoples in the Arctic. In this study, we sought to elicit Alaska Native (AN) community member and AN-serving healthcare providers' knowledge and perspectives on the CPT1A Arctic variant. Focus groups with community members and healthcare providers were held in two regions of Alaska between October 2018 and January 2019. Thematic analysis was used to identify recurring constructs. Knowledge and understanding about the CPT1A Arctic variant and its health impact varied, and participants were interested in learning more about it. Additional education for healthcare professionals was recommended to improve providers' ability to communicate with family caregivers about the Arctic variant. Engagement with AN community members identified opportunities to improve educational outreach via multiple modalities for providers and caregivers on the Arctic variant, which could help to increase culturally relevant guidance and avoid stigmatization, undue worry, and unnecessary intervention. Education and guidance on the care of infants and children homozygous for the CPT1A Arctic variant could improve care and reduce negative psychosocial effects.

Changes in brown adipose tissue induced by resveratrol and its analogue pterostilbene in rats fed with a high-fat high-fructose diet

Natural bioactive compounds have attracted a great deal of attention since some of them can act as thermogenesis activators. In recent years, special interest has been placed on resveratrol and its analogue pterostilbene, a dimethylether derivative that shows higher bioavailability. The aim of the present study is to compare the effects of resveratrol and its derivative pterostilbene on the thermogenic capacity of interscapular brown adipose tissue (iBAT) in rats under a high-fat high-fructose diet. Rats were divided into four experimental groups: control, high-fat high-fructose diet (HFHF) and HFHF diet supplemented with 30 mg/kg body weight/day of pterostilbene (PT30) or resveratrol (RSV30), for eight weeks. Weights of adipose tissues, iBAT triglycerides, carnitine palmitoyltransferase 1A (CPT1A) and citrate synthase (CS) activities, protein levels of uncoupling protein 1 (UCP1), sirtuins (SIRT1 and 3), AMP-activated protein kinase (AMPK), glucose transporter (GLUT4), fatty acid synthase (FAS), nuclear respiratory factor (NRF1), hormone-sensitive lipase (HSL), adipose triglyceride lipase (ATGL), CD36 and FATP1 fatty acid transporters, peroxisome proliferator-activated receptor gamma coactivator 1 (PGC1) activation and the batokines EPDR1 and NRG4 were assessed in iBAT. The results show that some key proteins related to thermogenesis were modified by either pterostilbene or resveratrol, although the lack of effects on other crucial proteins of the thermogenic machinery suggest that these compounds were not able to stimulate this process in iBAT. Overall, these data suggest that the effects of stilbenes on brown adipose tissue thermogenic capacity depend on the metabolic status, and more precisely on the presence or absence of obesity, although further studies are needed to confirm this hypothesis.

CPT1A mediates chemoresistance in human hypopharyngeal squamous cell carcinoma via ATG16L1-dependent cellular autophagy

Hypopharyngeal squamous cell carcinoma (HSCC) is a highly aggressive malignancy that constitutes approximately 95% of all hypopharyngeal carcinomas, and it carries a poor prognosis. The primary factor influencing the efficacy of anti-cancer drugs for this type of carcinoma is chemoresistance. Carnitine palmitoyltransferase 1A (CPT1A) has been associated with tumor progression in various cancers, including breast, gastric, lung, and prostate cancer. The inhibition or depletion of CPT1A can lead to apoptosis, curbing cancer cell proliferation and chemoresistance. However, the role of CPT1A in HSCC is not yet fully understood. In this study, we discovered that CPT1A is highly expressed in HSCC and is associated with an advanced T-stage and a poor 5-year survival rate among patients. Furthermore, the overexpression of CPT1A contributes to HSCC chemoresistance. Mechanistically, CPT1A can interact with the autophagy-related protein ATG16L1 and stimulate the succinylation of ATG16L1, which in turn drives autophagosome formation and autophagy. We also found that treatment with 3-methyladenine (3-MA) can reduce cisplatin resistance in HSCC cells that overexpress CPT1A. Our findings also showed that a CPT1A inhibitor significantly enhances cisplatin sensitivity both in vitro and in vivo. This study is the first to suggest that CPT1A has a regulatory role in autophagy and is linked to poor prognosis in HSCC patients. It presents novel insights into the roles of CPT1A in tumorigenesis and proposes that CPT1A could be a potential therapeutic target for HSCC treatment.

Loss of carnitine palmitoyltransferase 1a reduces docosahexaenoic acid-containing phospholipids and drives sexually dimorphic liver disease in mice

Background and aimsGenome and epigenome wide association studies identified variants in carnitine palmitoyltransferase 1a (CPT1a) that associate with lipid traits. The goal of this study was to determine the role of liver-specific CPT1a on hepatic lipid metabolism. Approach and resultsMale and female liver-specific knockout (LKO) and littermate controls were placed on a low-fat or high-fat diet (60% kcal fat) for 15 weeks. Mice were necropsied after a 16 h fast, and tissues were collected for lipidomics, matrix-assisted laser desorption ionization mass spectrometry imaging, kinome analysis, RNA-sequencing, and protein expression by immunoblotting. Female LKO mice had increased serum alanine aminotransferase levels which were associated with greater deposition of hepatic lipids, while male mice were not affected by CPT1a deletion relative to male control mice. Mice with CPT1a deletion had reductions in DHA-containing phospholipids at the expense of monounsaturated fatty acids (MUFA)-containing phospholipids in whole liver and at the level of the lipid droplet (LD). Male and female LKO mice increased RNA levels of genes involved in LD lipolysis (Plin2, Cidec, G0S2) and in polyunsaturated fatty acid metabolism (Elovl5, Fads1, Elovl2), while only female LKO mice increased genes involved in inflammation (Ly6d, Mmp12, Cxcl2). Kinase profiling showed decreased protein kinase A activity, which coincided with increased PLIN2, PLIN5, and G0S2 protein levels and decreased triglyceride hydrolysis in LKO mice. ConclusionsLiver-specific deletion of CPT1a promotes sexually dimorphic steatotic liver disease (SLD) in mice, and here we have identified new mechanisms by which females are protected from HFD-induced liver injury.