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Inorganic trivalent arsenic (iAsⅢ) at environmentally relevant levels has been found to cause developmental toxicity. Maternal exposure to iAsⅢ leads to enduring hepatic lipid deposition in later adult life. However, the exact mechanism in iAsⅢ induced hepatic developmental hazards is still unclear. In this study, we initially found that gestational exposure to iAsⅢ at an environmentally relevant concentration disturbs lipid metabolism and reduces levels of alpha-ketoglutaric acid (α-KG), an important mitochondrial metabolite during the citric acid cycle, in fetal livers. Further, gestational supplementation of α-KG alleviated hepatic lipid deposition caused by early-life exposure to iAsⅢ. This beneficial effect was particularly pronounced in female offspring. α-KG partially restored the β-oxidation process in hepatic tissues by hydroxymethylation modifications of carnitine palmitoyltransferase 1a (Cpt1a) gene during fetal development. Insufficient β-oxidation capacities probably play a crucial role in hepatic lipid deposition in adulthood following in utero arsenite exposure, which can be efficiently counterbalanced by replenishing α-KG. These results suggest that gestational administration of α-KG can ameliorate hepatic lipid deposition caused by iAsⅢ in female adult offspring partially through epigenetic reprogramming of the β-oxidation pathway. Furthermore, α-KG shows potential as an interventive target to mitigate the harmful effects of arsenic-induced hepatic developmental toxicity.

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.

Non-coding RNA is known to play a crucial role in the generation and deposition of intramuscular fat (IMF) in vertebrates by regulating the expression of genes involved in the synthesis, degradation and transportation of IMF. With the introduction of the competing endogenous RNA (ceRNA) hypothesis, circular RNA (circRNA) and long non-coding RNA (lncRNA) have been identified as natural "sponges" for microRNA (miRNA), yet their precise mechanisms and biological functions in chicken IMF are still not fully understood. In earlier research, we observed a significant association between Carnitine O-palmitoyltransferase 1, liver isoform (CPT1A) and fatty acid metabolism in chicken breast muscle. In this study, we utilized bioinformatics and previous sequencing data to construct a ceRNA regulatory network linked to intramuscular adipogenesis and deposition in chickens. This investigation aimed to unravel the post-transcriptional regulatory mechanism of CPT1A. The results showed that, functionally, CPT1A inhibited the proliferation and differentiation of intramuscular preadipocytes and affected the fatty acid composition of intramuscular adipocytes, and serving as a direct target of miR-181b-5p. In terms of mechanism, through a combination of bioinformatics analysis, dual luciferase reporter assays, quantitative real-time PCR (qRT-PCR), and Western blotting (WB), it was confirmed the interaction of a novel circRNA named circITGB5 with miR-181b-5p. CircITGB5 increased the expression of CPT1A mRNA and protein through post-transcriptional regulation. Acting as a ceRNA, circITGB5 competed with miR-181b-5p for binding to CPT1A, thereby shielding CPT1A from miR-181b-5p-mediated degradation. Subsequent rescue experiments confirmed the above conclusions. In conclusion, circITGB5 regulates the expression of the downstream target gene CPT1A by adsorption of miR-181b-5p, thereby regulating the proliferation and adipogenic differentiation of intramuscular preadipocytes. This discovery may have implications for achieving balanced breeding strategies aimed at enhancing the quality of chicken., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Anoikis resistance was a prominent hallmark of cancer metastasis, and lipo-genic characteristics have been identified as another metabolic alteration during tumorigenesis. However, their crosstalk has not been fully elucidated, especially in advanced esophageal squamous cell carcinoma (ESCC). In this study, we showed, for the first time, that the key enzyme carnitine O-palmitoyl transferase 1 (CPT1A), which is involved in fatty acid oxidation (FAO), was markedly upregulated in ESCC cells upon detached culture via a metabolism PCR array. Overexpression of CPT1A was associated with poor survival of ESCC patients and could protect ESCC cells from apoptosis via maintaining redox homeostasis through supply of GSH and NADPH. Mechanistically, detached culture conditions enhanced the expression of the transcription factor ETV4 and suppressed the expression of the ubiquitin enzyme RNF2, which were responsible for the elevated expression of CPT1A at the mRNA and protein levels, respectively. Moreover, genetic or pharmacologic disruption of CPT1A switched off the NADPH supply and therefore prevented the anchorage-independent growth of ESCC cells in vitro and lung metastases of xenografted tumor models in vivo. Collectively, our results provide novel insights into how ESCC cancer cells exploit metabolic switching to form distant metastases and some evidence for the link between anoikis and FAO.

Hepatic stellate cells (HSCs) are a major source of fibrogenic cells and play a central role in liver fibrogenesis. HSC activation depends on metabolic activation, for which it is well established that fatty acid oxidation (FAO) sustains their rapid proliferative rate. Studies have indicated that tanshinones inhibit HSC activation, however, the anti-fibrosis mechanisms of tanshinones are remain unclear. Herein, we reported that cryptotanshinone (CTS), a lipid-soluble ingredient of Salvia miltiorrhiza Bunge, exhibited the strongest inhibitory effects on HSC-LX2 proliferation and activation. CTS could induce lipocyte phenotype in mouse primary HSC and HSC-LX2. Transcriptomic sequencing and qPCR revealed that CTS regulated fatty acid metabolism and inhibited CPT1A and CPT1B expression. Target prediction suggested CTS regulates lipid metabolism by targeting STAT3. Mechanistically, the level of ATP and acetyl-CoA were reduced by the treatment of CTS, indicating that CTS could inhibit the level of FAO. Furthermore, CTS could inhibit the phosphorylation and nuclear translocation of STAT3. Additionally, CPT1A overexpression reversed the efficacy of CTS. Finally, CTS (40 mg/kg/day) attenuated CCl 4 -induced liver fibrosis and inhibited collagen production and HSC activation. Moreover, the results of immunofluorescence showed that α-SMA and p-STAT3 were co-located, and CTS could reduce the levels of p-STAT3 and α-SMA. In summary, CTS alleviated liver fibrosis by inhibiting the p-STAT3/CPT1A-dependent FAO both in vitro and in vivo, making it a potential candidate drug for the treatment of liver fibrosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Summary: The interrelation between hypoxia and immune response has pivotal roles in the pathogenesis of chronic metabolic diseases. However, the role of macrophage HIF-2α in NLRP3 inflammasome activation remains unclear. Here, we show that deficiency of HIF-2α in macrophages results in excessive activation of the NLRP3 inflammasome in a manner dependent on CPT1A-mediated enhancement of fatty acid oxidation (FAO). Mechanistically, HIF-2α binds directly to the Cpt1a promoter and is involved in the regulation of H3K27me3 methylation during NLRP3 inflammasome activation. Myeloid-specific Hif2α knockout mice exhibit exacerbated insulin resistance and increased activation of NLRP3 inflammasome in macrophages. Overexpression of the Hif2α gene or stabilization of the protein by FG-4592 ameliorates insulin resistance and reduces NLRP3 inflammasome activation in macrophages. Taken together, our results suggest that macrophage HIF-2α inhibits FAO-mediated activation of the NLRP3 inflammasome and alleviates insulin resistance.

Excessive accumulation of extracellular matrix (ECM) is the hallmark of fibrotic diseases. In the kidney, it is the final common pathway of prevalent diseases, leading to chronic renal failure. While cytokines such as TGF-β play a fundamental role in myofibroblast transformation, recent work has shown that mitochondrial dysfunction and defective fatty acid oxidation (FAO), which compromise the main source of energy for renal tubular epithelial cells, have been proposed to be fundamental contributors to the development and progression of kidney fibrosis. MicroRNAs (miRNAs), which regulate gene expression post-transcriptionally, have been reported to control renal fibrogenesis. To identify miRNAs involved in the metabolic derangement of renal fibrosis, we performed a miRNA array screen in the mouse model of unilateral ureteral obstruction (UUO). MiR-150-5p and miR-495-3p were selected for their link to human pathology, their role in mitochondrial metabolism and their targeting of the fatty acid shuttling enzyme CPT1A. We found a 2- and 4-fold upregulation of miR-150-5p and miR-495-5p, respectively, in both the UUO and the folic acid induced nephropathy (FAN) models, while TGF-β1 upregulated their expressions in the human renal tubular epithelial cell line HKC-8. These miRNAs synergized with TGF-β regarding its pro-fibrotic effect by enhancing the fibrosis-associated markers Acta2, Col1α1 and Fn1. Bioenergetics studies showed a reduction of FAO-associated oxygen consumption rate (OCR) in HKC-8 cells in the presence of both miRNAs. Consistently, expression levels of their mitochondrial-related target genes CPT1A, PGC1α and the mitochondrial transcription factor A (TFAM), were reduced by half in renal epithelial cells exposed to these miRNAs. By contrast, we did not detect changes in mitochondrial mass and transmembrane potential (ΔѰm) or mitochondrial superoxide radical anion production. Our data support that miR-150 and miR-495 may contribute to renal fibrogenesis by aggravating the metabolic failure critically involved in tubular epithelial cells, ultimately leading to fibrosis.

We examined the effects of curcumin, quercetin, and atorvastatin on the hepatic fibrosis through measurement of the protein levels of phospho-AMP-activated protein kinase (p-AMPK) and phospho-acetyl-CoA carboxylase (p-ACC) and gene expression of lipogenic genes in bile duct ligation (BDL)-induced fibrotic rats. We divided male Wistar rats into 8 groups (n = 8 for each), four of which were sham and the remaining four received BDL operations. Each rat in the sham or BDL groups was administered quercetin (30 mg/kg/day), curcumin (100 mg/kg) or atorvastatin (15 mg/kg) for 4 weeks. We found that curcumin, quercetin, and atorvastatin treatment led to up-regulation of p-AMPK and carnitine palmitoyl transferase (CPT1a). However, they suppressed the BDL-mediated increase in sterol regulatory element-binding protein-1c (SREBP-1c), ACC1, fatty acid synthase (FAS) and beta hydroxy beta methylglutaryl-CoA reductase (HMGCR) gene expression (P

Introduction: Preeclampsia (PE) refers to a syndrome of new-onset hypertension with multisystem involvement and damage after 20 weeks of gestation. Defective placentation due to dysregulated behaviors of trophoblast cells is considered a predominant cause of PE., Methods: Immunofluorescence (if) and Western blot were used to detect the expression and localization of Carnitine palmitoyltransferase 1A (CPT1A) in placenta. CPT1A protein was overexpressed/knocked down in HTR8/SVneo cells by lentiviral/siRNA interference method. CCK-8 Assay, Western blot, flow cytometry, Wound healing and Transwell assay were used to detect the functional impact of CPT1A on HTR8/SVneo cells. Transcriptomics and bioinformatics analysis were used to predict the possible pathway of CPT1A participating in PE., Results: CPT1A was upregulated in preeclamptic placentas when compared with normal controls. The abnormal expression of CPT1A in HTR8/SVneo cells is associated with the invasion and migration of HTR8/SVneo cells but is not related to the proliferation, cycle, and apoptosis of HTR8/SVneo cells. The results of Transcriptomic and Western blots suggest that phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway are activated in the si-CPT1A-1796 group. Compared with the si-NC group, the epithelial-mesenchymal transition (EMT) process of HTR8/SVneo cells in the si-CPT1A- 1796 group was significantly enhanced., Discussion: CPT1A may participate in the pathogenesis of PE by inhibiting the EMT process of HTR8/SVneo cells through the PI3K/AKT/mTOR signaling axis. Thus, the newly unveiled novel function of CPT1A in PE via the PI3K/Akt/mTOR pathway provides a novel insight into the pathogenesis of PE., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2023. Published by Elsevier Ltd.)

Competing Interests: Declaration of Competing Interest KAM is a site principal investigator for studies sponsored by LivaNova, GeneTx, and Ionis. HP reports no relevant conflicts of interest.

Background & Aims: The pathogenesis of liver fibrosis requires activation of hepatic stellate cells (HSCs); once activated, HSCs lose intracellular fatty acids but the role of fatty acid oxidation and carnitine palmitoyltransferase 1A (CPT1A) in this process remains largely unexplored., Methods: CPT1A was found in HSCs of patients with fibrosis. Pharmacological and genetic manipulation of CPT1A were performed in human HSC cell lines and primary HCSs. Finally, we induced fibrosis in mice lacking CPT1A specifically in HSCs., Results: Herein, we show that CPT1A expression is elevated in HSCs of patients with non-alcoholic steatohepatitis, showing a positive correlation with the fibrosis score. This was corroborated in rodents with fibrosis, as well as in primary human HSCs and LX-2 cells activated by transforming growth factor β1 (TGFβ1) and fetal bovine serum (FBS). Furthermore, both pharmacological and genetic silencing of CPT1A prevent TGFβ1- and FBS-induced HSC activation by reducing mitochondrial activity. The overexpression of CPT1A, induced by saturated fatty acids and reactive oxygen species, triggers mitochondrial activity and the expression of fibrogenic markers. Finally, mice lacking CPT1A specifically in HSCs are protected against fibrosis induced by a choline-deficient high-fat diet, a methionine- and choline-deficient diet, or treatment with carbon tetrachloride., Conclusions: These results indicate that CPT1A plays a critical role in the activation of HSCs and is implicated in the development of liver fibrosis, making it a potentially actionable target for fibrosis treatment., Lay Summary: We show that the enzyme carnitine palmitoyltransferase 1A (CPT1A) is elevated in hepatic stellate cells (HSCs) in patients with fibrosis and mouse models of fibrosis, and that CPT1A induces the activation of these cells. Inhibition of CPT1A ameliorates fibrosis by preventing the activation of HSCs., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest related to the study. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

In the current work, a series of novel 4-benzyloxy and 4-(2-phenylethoxy) chalcone fibrate hybrids (10a-o) and (11a-e) were synthesized and evaluated as new PPARα agonists in order to find new agents with higher activity and fewer side effects. The 2-propanoic acid derivative 10a and the 2-butanoic acid congener 10i showed the best overall PPARα agonistic activity showing E max % values of 50.80 and 90.55%, respectively, and EC 50 values of 8.9 and 25.0 μM, respectively, compared to fenofibric acid with E max  = 100% and EC 50  = 23.22 μM, respectively. These two compounds also stimulated carnitine palmitoyltransferase 1A gene transcription in HepG2 cells and PPARα protein expression. Molecular docking simulations were performed for the newly synthesized compounds to study their predicted binding pattern and energies in PPARα active site to rationalize their promising activity. In vivo, compounds 10a and 10i elicited a significant hypolipidemic activity improving the lipid profile in triton WR-1339-induced hyperlipidemic rats, including serum triglycerides, total cholesterol, LDL, HDL and VLDL levels. Compound 10i possessed better anti-hyperlipidemic activity than 10a. At a dose of 200 mg/kg, it demonstrated significantly lower TC, TG, LDL and VLDL levels than that of fenofibrate at the same dose with similar HDL levels. Compounds 10i and 10a possessed atherogenic indices (CRR, AC, AI, CRI-II) like that of fenofibrate. Additionally, a promising antioxidant activity indicated by the increased tissue reduced glutathione and plasma total antioxidant capacity with decreased plasma malondialdehyde levels was demonstrated by compounds 10a and 10i. No histopathological alterations were recorded in the hepatic tissue of compound 10i (200 mg/kg)., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Carnitine palmitoyltransferase 1A (CPT1A) deficiency is a rare disorder of hepatic long-chain fatty acid oxidation. Most patients with CPT1A deficiency present with hypoketotic hypoglycemia and hepatic encephalopathy. We describe an atypical case of an 8-year-old male with CPT1A deficiency presenting with chronic liver steatosis and cirrhosis. He also had a history of developmental delay, autism spectrum disorder, and mild dysmorphic features of unknown cause. His newborn screening test suggested CPT1A deficiency, but confirmatory biochemical testing was not conclusive. The patient never experienced a metabolic crisis. At age six, hepatomegaly was detected. Further investigations showed transaminitis, hepatosteatosis and cirrhosis. Repeat acylcarnitine profile and total/free carnitine were consistent with CPT1A deficiency. The CPTI enzyme activity was 18% of normal on fibroblast enzyme assay. A novel homozygous variant in the CPT1A gene, c.1394G > A (p.Gly465Glu) was identified from whole-exome sequencing. To our knowledge, the patient is the first reported individual with CPT1A deficiency and chronic liver steatosis and fibrosis. Developmental delay and autistic spectrum disorder are not typical features of CPT1A deficiency, given that the patient never experienced any metabolic decompensation., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Background: Gastric cancer (GC) has a high rate of metastasis which thereason leading to death. Carnitine palmitoyl transferase 1a (CPT1A) has been reported to play a critical obstacle to various types of cancer progression, which is an attractive focus in anti-cancer therapy. However, the underlying molecular mechanisms of CPT1A involved in GC have not been clarified clear., Methods: To determine the expression of CPT1A in human GC tissues and cells and illustrate whether it is correlated with the clinical pathologic characteristics and prognosis in GC patients. Its roles and potential mechanisms in regulating tumor growth and invasion were evaluated by CPT1A knockdown/overexpression of GC cells in vitro., Results: Marked upregulation of CPT1A protein expression was observed in GC cells and tissues, which was associated with grade, pathological stage, lymph node metastasis and poor prognosis in patients with GC. CPT1A overexpression also promoted the proliferation, invasion, EMT process of GC cells. In addition, CPT1A upregulation activated GC cell fatty acid oxidation (FAO) via increasing NADP + /NADPH ratio, whereas inhibiting of FAO abolished the effects of CPT1A on GC cell proliferation and migration., Conclusion: Our results examine that CPT1A-mediated FAO activation increases GC cell proliferation and migration, supporting that CPT1A is a useful prognostic biomarker and an attractive focus for GC., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Epigenome-wide association studies identified the cg00574958 DNA methylation site at the carnitine palmitoyltransferase-1A (CPT1A) gene to be associated with reduced risk of metabolic diseases (hypertriglyceridemia, obesity, type 2 diabetes, hypertension, metabolic syndrome), but the mechanism underlying these associations is unknown., Objectives: We aimed to elucidate whether carbohydrate and fat intakes modulate cg00574958 methylation and the risk of metabolic diseases., Methods: We examined associations between carbohydrate (CHO) and fat (FAT) intake, as percentages of total diet energy, and the CHO/FAT ratio with CPT1A-cg00574958, and the risk of metabolic diseases in 3 populations (Genetics of Lipid Lowering Drugs and Diet Network, n = 978; Framingham Heart Study, n = 2331; and REgistre GIroní del COR study, n = 645) while adjusting for confounding factors. To understand possible causal effects of dietary intake on the risk of metabolic diseases, we performed meta-analysis, CPT1A transcription analysis, and mediation analysis with CHO and FAT intakes as exposures and cg00574958 methylation as the mediator., Results: We confirmed strong associations of cg00574958 methylation with metabolic phenotypes (BMI, triglyceride, glucose) and diseases in all 3 populations. Our results showed that CHO intake and CHO/FAT ratio were positively associated with cg00574958 methylation, whereas FAT intake was negatively correlated with cg00574958 methylation. Meta-analysis further confirmed this strong correlation, with β = 58.4 ± 7.27, P = 8.98 x 10-16 for CHO intake; β = -36.4 ± 5.95, P = 9.96 x 10-10 for FAT intake; and β = 3.30 ± 0.49, P = 1.48 x 10-11 for the CHO/FAT ratio. Furthermore, CPT1A mRNA expression was negatively associated with CHO intake, and positively associated with FAT intake, and metabolic phenotypes. Mediation analysis supports the hypothesis that CHO intake induces CPT1A methylation, hence reducing the risk of metabolic diseases, whereas FAT intake inhibits CPT1A methylation, thereby increasing the risk of metabolic diseases., Conclusions: Our results suggest that the proportion of total energy supplied by CHO and FAT can have a causal effect on the risk of metabolic diseases via the epigenetic status of CPT1A.Study registration at https://www.clinicaltrials.gov/: the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN)-NCT01023750; and the Framingham Heart Study (FHS)-NCT00005121., (Published by Oxford University Press on behalf of the American Society for Nutrition 2020.)

Background: Dyslipidemia causes renal damage; however, the detailed molecular mechanism has not been clarified. It is known that carnitine palmitoyl transferase 1-a (CPT1a) gene encodes an enzyme involved in fatty acid oxidation and, therefore, lipid content. In the present study, we investigated whether the accumulation of lipids induced by 7-ketocholesterol (7-KC) in tubular epithelial cells produce a fibrotic and inflammatory response through CPT1a., Methods: Using an epithelial cell line, NRK-52E, we determine if intracellular accumulation of 7-KC modulates profibrotic and inflammatory events through CPT1a gene expression. In addition, the direct effects of CPT1a genetic modification has been studied., Results: Our results revealed that high levels of 7-KC induce increased expression of CPT1a, TGF-β1, α- SMA and NLRP3 that was correlated with lipid content. GW3965 treatment, which have shown to facilitate the efflux of cholesterol, eliminated the intracellular lipid droplets of 7-KC laden cells and decreased the expression of CPT1a, TGF-β1, α- SMA and NLRP3. Furthermore, CPT1a Knockdown and C75 pre-treatment increased lipid content but decreased TGF-β1, α- SMA and NLRP3., Conclusions: Our findings reveal that the profibrotic effect of 7-KC on renal epithelial cells are mediated by CPT1a overexpression, which acts on TGF-β1, α-SMA and NLRP3. Thus, CPT1a downregulation protects against 7-KC-induced fibrosis in tubular epithelial cells by downregulating TGF-β1, α- SMA and NLRP3., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

During embryonic development, lymphatic endothelial cells (LECs) differentiate from venous endothelial cells (VECs), a process that is tightly regulated by several genetic signals. While the aquatic zebrafish model is regularly used for studying lymphangiogenesis and offers the unique advantage of time-lapse video-imaging of lymphatic development, some aspects of lymphatic development in this model differ from those in the mouse. It therefore remained to be determined whether fatty acid β-oxidation (FAO), which we showed to regulate lymphatic formation in the mouse, also co-determines lymphatic development in this aquatic model. Here, we took advantage of the power of the zebrafish embryo model to visualize the earliest steps of lymphatic development through time-lapse video-imaging. By targeting zebrafish isoforms of carnitine palmitoyltransferase 1a (cpt1a), a rate controlling enzyme of FAO, with multiple morpholinos, we demonstrate that reducing CPT1A levels and FAO flux during zebrafish development impairs lymphangiogenic secondary sprouting, the initiation of lymphatic development in the zebrafish trunk, and the formation of the first lymphatic structures. These findings not only show evolutionary conservation of the importance of FAO for lymphatic development, but also suggest a role for FAO in co-regulating the process of VEC-to-LEC differentiation in zebrafish in vivo., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Cancer cells are characterized by altered metabolic processes. Recent evidence of metabolic alterations has indicated that the fatty acid oxidation (FAO) pathway is used as a carbon source for anabolic processes in some tumors, thus making this pathway a potential target for therapy. The carnitine palmitoyltransferase (CPT; EC 2.3.1.21) enzyme transfers long-chain fatty acids from the cytosol to the mitochondrial matrix for β-oxidation. Because carnitine palmitoyl transferase 1a (CPT1a) is the rate-limiting enzyme for FAO, the authors evaluated the effects of CPT1A knock-down in BRAF V600E melanoma cell lines. The results showed that knock-down of CPT1A inhibited FAO and that CPT1A is critical for malignant V600E melanoma cells, particularly BRAF V600E melanoma cells. The proliferation and tumorigenesis in V600E melanoma were decrease after CPT1A knockdown. These results suggest that therapy for BRAF V600E melanoma can include targeting metabolic alterations. CPT1A is more important for lipid synthesis in V600E mutant melanoma cells than in wild-type BRAF melanoma cells., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Hypometabolism is a strategy favored by many species to survive extreme environmental stresses such as low temperatures, lack of food sources or anoxic conditions. Mammalian hibernation and insect cold hardiness are well-documented examples of natural models utilizing metabolic rate depression when confronted with such conditions. A plethora of metabolic and molecular changes must occur in these species to regulate this process. A recently discovered family of short non-coding nucleic acids, the miRNAs, is rapidly emerging as a potential modulator of cold tolerance in different species. In this review, we present the current knowledge associated with physiological and biochemical adaptations at low temperatures. We further explore the cascade of miRNA biogenesis as well as miRNA target recognition and translational repression. Finally, we introduce miRNAs shown to be differentially regulated in selected species when confronted with low temperatures and discuss the potential transcript targets regulated by these "CryomiRs"., (© 2013.)