BACKGROUND: Secondary carnitine deficiency in patients with anorexia nervosa has been rarely reported. This study aimed to investigate the occurrence of carnitine deficiency in severely malnourished patients with eating disorders during refeeding and assess its potential adverse effects on treatment outcomes.
METHODS: In a cohort study of 56 female inpatients with eating disorders at a single hospital from March 2010 to December 2020, we measured plasma free carnitine (FC) levels and compared to those of a healthy control group (n = 35). The patients were categorized into three groups based on FC levels: FC deficiency (FC< 20 µmol/L), FC pre-deficiency (20 µmol/L ≤ FC< 36 µmol/L), and FC normal (36 µmol/L ≤ FC).
RESULTS: Upon admission, the patients had a median age of 26 years (interquartile range [IQR]: 21-35) and a median body mass index (BMI) of 13.8 kg/m2 (IQR: 12.8-14.8). Carnitine deficiency or pre-deficiency was identified in 57% of the patients. Hypocarnitinemia was associated with a decline in hemoglobin levels during refeeding (odds ratio [OR]: 0.445; 95% confidence interval [CI]: 0.214-0.926, p = 0.03), BMI at admission (OR: 0.478; 95% CI: 0.217-0.874, p = 0.014), and moderate or greater hepatic impairment at admission (OR: 6.385; 95% CI: 1.170-40.833, p = 0.032).
CONCLUSIONS: Hypocarnitinemia, particularly in cases of severe undernutrition (BMI< 13 kg/m2 at admission) was observed in severely malnourished patients with eating disorders during refeeding, a critical metabolic transition phase. Moderate or severe hepatic impairment at admission was considered a potential indicator of hypocarnitinemia. Although hypocarnitinemia was not associated with any apparent adverse events other than anemia during refeeding, the possibility that carnitine deficiency may be a risk factor for more serious complications during sudden increases in energy requirements associated with changes in physical status cannot be denied. Further research on the clinical significance of hypocarnitinemia in severely malnourished patients with eating disorders is warranted.
Carnitine is an amino acid derivative that plays an important role in the promotion and regulation of fatty acid metabolism, and carnitine deficiency is assumed in patients with anorexia nervosa associated with chronic starvation, but there are few reports on this issue. This study represents the inaugural documentation of hypocarnitinemia in severely malnourished patients with eating disorders, including anorexia nervosa. Hypocarnitinemia, particularly in cases of severe undernutrition (BMI < 13 kg/m2) was observed during refeeding, a critical metabolic transition phase. Moderate or severe hepatic impairment was considered a potential indicator of hypocarnitinemia. Although no apparent association with adverse events other than anemia during refeeding was identified, clinical manifestations of hypocarnitinemia may occur when a sudden increase in energy demand is added to a change in the physical condition of the patient group. Further investigation is required to determine the clinical significance of hypocarnitinemia.

BACKGROUND: Y-box binding protein 1 (YBX1) is a DNA/RNA binding protein known to contribute to the progression of various malignancies, however, a comprehensive pan-cancer analysis to investigate YBX1 across a broad spectrum of cancer types has not yet been conducted.
METHODS: We utilized the TIMER database for a comprehensive pan-cancer analysis and assessed YBX-1 expression via the TCGA and GEO databases. The relationship between YBX-1 expression and tumor-infiltrating cells was examined using TIMER and the R programming language. To evaluate the prognostic value of YBX1, we performed Kaplan-Meier plots and Cox regression analyses. Through LinkedOmics, we identified genes significantly correlated with YBX-1. The WEB-based Gene SeT AnaLysis Toolkit was used for KEGG pathway enrichment analysis. Additionally, using shRNA-mediated knockdown, we explored the potential role of YBX1 in tumor cell biology.
RESULTS: Our study identifies pronounced overexpression of YBX-1 across multiple cancer types, correlating with adverse outcomes, notably in liver hepatocellular carcinoma (LIHC). A distinct association between elevated YBX-1 expression and heightened immune cell infiltration suggests YBX-1\'s potential role in reshaping the tumor microenvironment. Intriguingly, our KEGG pathway analysis indicated a tight nexus between YBX-1 expression and lipid metabolism. Moreover, the suppression of YBX-1 via shRNA revealed diminished cellular proliferation and marked reductions in crucial molecules steering the fatty acid synthesis pathway, implicating YBX-1\'s potential regulatory role in lipid metabolism within LIHC.
CONCLUSIONS: YBX-1 serves as a favorable prognostic indicator in various cancers, particularly in liver hepatocellular carcinoma. Targeting YBX1 in HCC offers potential therapeutic strategies. This work paves the way for fresh insights into targeted therapeutic approaches for cancers, especially benefiting liver hepatocellular carcinoma patients.

The bioavailability of long-chain omega-3 polyunsaturated fatty acids (n3 PUFA) can be affected by the form in which they are bound. An alternative source of n3 PUFA is Calanus finmarchicus oil (CO), which, unlike fish oil (FO) and krill oil (KO), contains fatty acids primarily bound as wax esters. Recent studies have shown that n3 PUFA from CO are bioavailable to humans, but CO has not been compared to other marine oils such as FO or KO. Therefore, the aim of this study was to investigate the influence of 12 weeks supplementation with CO, FO and KO on the long-term n3 PUFA status in healthy volunteers. The Omega-3 Index (O3I), defined as red blood cell EPA + DHA content as a percentage of total identified fatty acids, was used as a measure to assess n3 PUFA status. Sixty-two participants (mean ± standard deviation [SD] age: 29.7 ± 8.43 years) completed the randomized parallel group study (CO group: n = 21, 4 capsules/day, EPA + DHA dose: 242 mg/day; FO group: n = 22, 1 capsule/day, EPA + DHA dose: 248 mg/day; KO group: n = 19, 2 capsules/day, EPA + DHA dose: 286 mg/day). At baseline, the three groups showed comparable (mean ± SD) O3I values (CO: 5.13 ± 1.12%, FO: 4.90 ± 0.57%, KO: 4.87 ± 0.77%). The post-interventional (mean ± SD) O3I increase was comparable between the three groups (CO: 1.09 ± 0.55%; FO: 1.0 ± 0.53%; KO: 1.15 ± 0.65%, all p < 0.001). The study confirms that CO can increase the n3 PUFA status comparable to FO and KO and is therefore an alternative marine source of bioavailable n3 PUFA, especially with regard to sustainability.

Determining myocardial infarction (MI) and mechanical asphyxia (MA) was one of the most challenging tasks in forensic practice. The present study aimed to investigate the potential of fatty acid (FAs) metabolism, and lipid alterations in determining MI and MA. MA and MI mouse models were constructed, and metabolic profiles were obtained by LC-MS-based untargeted metabolomics. The metabolic alterations were explored using the PCA, OPLS-DA, the Wilcoxon test, and fold change analysis. The contents of lipid droplets (LDs) were detected by the transmission scanning electron microscope and Oil red O staining. The immunohistochemical assay was performed to detect CD36 and dysferlin. The ceramide was assessed by LC-MS. PCA showed considerable differences in the metabolite profiles, and the well-fitting OPLS-DA model was developed to screen differential metabolites. Thereinto, 9 metabolites in the MA were reduced, while metabolites were up- and down-regulated in MI. The increased CD36 suggested that MI and MA could enhance the intake of FAs and disturb energy metabolism. The increased LDs, decreased dysferlin, and increased ceramide (C18:0, C22:0, and C24:0) were observed in MI groups, confirming the lipid deposition. The present study indicated significant differences in myocardial FAs metabolism and lipid alterations between MI and MA, suggesting that FAs metabolism and related proteins, certain ceramide may harbor the potential as biomarkers for discrimination of MI and MA.

BACKGROUND: The application of cold exposure has emerged as an approach to enhance whole-body lipid catabolism. The global effect of cold exposure on the lipidome in humans has been reported with mixed results depending on intensity and duration of cold.
METHODS: This secondary study was based on data from a previous randomized cross-over trial (ClinicalTrials.gov ID: NCT03012113). We performed sequential lipidomic profiling in serum during 120 min cold exposure of human volunteers. Next, the intracellular lipolysis was blocked in mice (eighteen 10-week-old male wild-type mice C57BL/6J) using a small-molecule inhibitor of adipose triglyceride lipase (ATGL; Atglistatin), and mice were exposed to cold for a similar duration. The quantitative lipidomic profiling was assessed in-depth using the Lipidyzer platform.
RESULTS: In humans, cold exposure gradually increased circulating free fatty acids reaching a maximum at 60 min, and transiently decreased total triacylglycerols (TAGs) only at 30 min. A broad range of TAG species was initially decreased, in particular unsaturated and polyunsaturated TAG species with ≤5 double bonds, while after 120 min a significant increase was observed for polyunsaturated TAG species with ≥6 double bonds in humans. The mechanistic study in mice revealed that the cold-induced increase in polyunsaturated TAGs was largely prevented by blocking adipose triglyceride lipase.
CONCLUSIONS: We interpret these findings as that cold exposure feeds thermogenic tissues with TAG-derived fatty acids for combustion, resulting in a decrease of circulating TAG species, followed by increased hepatic production of polyunsaturated TAG species induced by liberation of free fatty acids stemming from adipose tissue.
BACKGROUND: This work was supported by the Netherlands CardioVascular Research Initiative: \'the Dutch Heart Foundation, Dutch Federation of University Medical Centers, the Netherlands Organisation for Health Research and Development and the Royal Netherlands Academy of Sciences\' [CVON2017-20 GENIUS-II] to Patrick C.N. Rensen. Borja Martinez-Tellez is supported by individual postdoctoral grant from the Fundación Alfonso Martin Escudero and by a Maria Zambrano fellowship by the Ministerio de Universidades y la Unión Europea - NextGenerationEU (RR_C_2021_04). Lucas Jurado-Fasoli was supported by an individual pre-doctoral grant from the Spanish Ministry of Education (FPU19/01609) and with an Albert Renold Travel Fellowship from the European Foundation for the Study of Diabetes (EFSD). Martin Giera was partially supported by NWO XOmics project #184.034.019.

Zeugodacus cucurbitae (Coquillett), Bactrocera dorsalis (Hendel), and Ceratitis capitata (Wiedemann) are important pests of fruit and vegetable crops and are difficult to control because of their rapid reproduction rate and egg production. To investigate the key genes regulating reproduction in three fruit fly species, we selected genomic information of three fruit fly species, screened specific genes and single-copy homolog genes, and performed KEGG and GO enrichment analysis on specific genes and single-copy homolog genes of the strong positive select (SP); the results showed that Z. cucurbitae (Coquillett), B. dorsalis (Hendel), and C. capitata (Wiedemann) had seven, 11, and one Vitellogenin-related genes, respectively; Z. cucurbitae (Coquillett) had 84 specific genes enriched in immune system-related pathways; B. dorsalis (Hendel) had 1,121 specific genes enriched in signaling pathways related to cell growth and differentiation; C. capitata (Wiedemann) had 42 specific genes enriched in the degradation and metabolism pathways of exogenous organisms; Z. cucurbitae (Coquillett) may have a stronger immune system; B. dorsalis (Hendel) has a faster developmental and reproductive rate; and C. capitata (Wiedemann) has a higher detoxification capacity. Only one SP single-copy homolog gene (gene name: very long-chain specific acyl-CoA dehydrogenase, mitochondrial) is enriched in the fatty acid metabolic pathway in both Z. cucurbitae (Coquillett) and B. dorsalis (Hendel) as well as in Z. cucurbitae (Coquillett) and C. capitata (Wiedemann). This study provides a molecular basis for studying the reproductive mechanisms of three fruit fly species and provides a scientific basis for developing effective control strategies for fruit flies.

Saroglitazar, being a dual PPAR-α/γ agonist, has shown beneficial effect in diabetic dyslipidemia and hypertriglyceridemia. Fibrates are commonly used to treat severe hypertriglyceridemia. However, the effect of saroglitazar in patients with moderate to severe hypertriglyceridemia was not evaluated. We conducted a study to compare the efficacy and safety of saroglitazar (4 mg) with fenofibrate (160 mg) in patients with moderate to severe hypertriglyceridemia. This was a multicenter, randomized, double-blinded, double-dummy, active-control, and noninferiority trial in adult patients with fasting triglyceride (TG) levels of 500-1,500 mg/dl. The patients were randomized in a 1:1 ratio to receive daily dose of saroglitazar or fenofibrate for 12 weeks. The primary efficacy end point was the percent change in TG levels at week 12 relative to baseline. The study comprised of 41 patients in the saroglitazar group and 41 patients in the fenofibrate group. We found that the percent reduction from baseline in TG levels at week 12 was significantly higher in the saroglitazar group (least square mean = -55.3%; SE = 4.9) compared with the fenofibrate group (least square mean = -41.1%; SE = 4.9; P = 0.048). Overall, 37 treatment-emergent adverse events (AEs) were reported in 24 patients (saroglitazar: 13; fenofibrate: 11). No serious AEs were reported, and no patient discontinued the study because of AEs. We conclude that saroglitazar (4 mg) is noninferior to fenofibrate (160 mg) in reducing TG levels after 12 weeks of treatment, was safe, and well tolerated.

Fatty acid beta-oxidation is a key process in mammalian lipid catabolism. Disturbance of this process results in severe clinical symptoms, including dysfunction of the liver, a major beta-oxidizing tissue. For a thorough understanding of this process, a comprehensive analysis of involved fatty acid and acyl-carnitine intermediates is desired, but capable methods are lacking. Here, we introduce oxaalkyne and alkyne fatty acids as novel tracers to study the beta-oxidation of long- and medium-chain fatty acids in liver lysates and primary hepatocytes. Combining these new tracer tools with highly sensitive chromatography and mass spectrometry analyses, this study confirms differences in metabolic handling of fatty acids of different chain length. Unlike longer chains, we found that medium-chain fatty acids that were activated inside or outside of mitochondria by different acyl-CoA synthetases could enter mitochondria in the form of free fatty acids or as carnitine esters. Upon mitochondrial beta-oxidation, shortened acyl-carnitine metabolites were then produced and released from mitochondria. In addition, we show that hepatocytes ultimately also secreted these shortened acyl chains into their surroundings. Furthermore, when mitochondrial beta-oxidation was hindered, we show that peroxisomal beta-oxidation likely acts as a salvage pathway, thereby maintaining the levels of shortened fatty acid secretion. Taken together, we conclude that this new method based on oxaalkyne and alkyne fatty acids allows for metabolic tracing of the beta-oxidation pathway in tissue lysate and in living cells with unique coverage of metabolic intermediates and at unprecedented detail.

Although the gut microbiome has been associated with dietary patterns linked to health, microbial metabolism is not well characterized. This ancillary study was a proof of principle analysis for a novel application of metaproteomics to study microbial protein expression in a controlled dietary intervention. We measured the response of the microbiome to diet in a randomized crossover dietary intervention of a whole-grain, low glycemic load diet (WG) and a refined-grain, high glycemic load diet (RG). Total proteins in stools from 9 participants at the end of each diet period (n = 18) were analyzed by LC MS/MS and proteins were identified using the Human Microbiome Project (HMP) human gut microbiome database and UniProt human protein databases. T-tests, controlling for false discovery rate (FDR) <10%, were used to compare the Gene Ontology (GO) biological processes and bacterial enzymes between the two interventions. Using shotgun proteomics, more than 53,000 unique peptides were identified including microbial (89%) and human peptides (11%). Forty-eight bacterial enzymes were statistically different between the diets, including those implicated in SCFA production and degradation of fatty acids. Enzymes associated with degradation of human mucin were significantly enriched in the RG diet. These results illustrate that the metaproteomic approach is a valuable tool to study the microbial metabolism of diets that may influence host health.

Elevated stearoyl-CoA desaturase 1 (SCD-1) activity showed associations with obesity in cross-sectional studies. In non-pregnant populations, nutrition regulates SCD-1 transcription and activity.
To investigate the longitudinal associations of maternal and fetal SCD-1 activity markers with infant anthropometry up to 2 years of age, and to explore how selected dietary intakes modulate SCD-1 activity in pregnancy.
As a secondary analysis from the ROLO intervention study, which was conducted in a population at risk for macrosomia, non-esterified fatty acids (NEFA) from maternal plasma at 13 and 28 weeks\' gestation and in cord blood were measured via liquid-chromatography-mass-spectrometry. Fatty acid ratios 18:1/18:0 and 16:1/16:0 were used as markers for SCD-1 activity (\'desaturation indices\', DIs). Relationships of DIs with infant anthropometry up to 2 years of age and maternal dietary parameters during pregnancy were investigated using adjusted linear regression models and p-values correction for multiple testing.
18:1/18:0, but not 16:1/16:0, was associated with measures of infant anthropometry at birth (maternal and fetal markers) and up to 2 years of age (maternal markers only). Dietary intakes did not show strong associations with 18:1/18:0, but 16:1/16:0 was associated with absolute and relative dietary intakes.
In a population at risk for macrosomia, maternal SCD-1 activity measured via 18:1/18:0 was involved in the fetal programming of infant obesity, but could not be substantially modulated by short-term diet in pregnancy.
ISRCTN Registration number: ISRCTN54392969 (http://www.isrctn.com/ISRCTN54392969).