BACKGROUND: Evidence regarding metabolic alterations associated with maternal antenatal depression (AD) is limited, and their role as potential biomarkers improving the prediction of AD and adverse child birth, neurodevelopmental, and mental health outcomes remains unexplored.
METHODS: In a cohort of 331 mother-child dyads, we studied associations between AD (history of medical register diagnoses and/or Center of Epidemiological Studies Depression Scale score during pregnancy≥20) and 95 metabolic measures analyzed three times during pregnancy. We tested whether the AD-related metabolic measures increased variance explained in AD over its risk factors, and in child birth, neurodevelopmental, and mental health outcomes over AD. We replicated the findings in a cohort of 416 mother-child dyads.
RESULTS: Elastic net regression identified 15 metabolic measures that collectively explained 25% (p<0.0001) of variance in AD, including amino and fatty acids, glucose, inflammation, and lipids. These metabolic measures increased the variance explained in AD over its risk factors (32.3%,p<0.0001 vs. 12.6%,p=0.004), and in child gestational age (9.0%,p<0.0001 vs. 0.7%, p=0.34), birth weight(9.0%,p=0.03 vs. 0.7%, p=0.33), developmental milestones at the age of 2.3-5.7 years(21.0%,p=0.002 vs. 11.6%,p<0.001) and any mental or behavioral disorder by the age of 13.1-16.8 years(25.2%,p=0.03 vs. 5.0%,p=0.11) over AD, child sex and age. These findings replicated in the independent cohort.
CONCLUSIONS: AD is associated with alterations in 15 metabolic measures, which collectively improve the prediction of AD over its risk factors, and birth, neurodevelopmental and mental health outcomes of the child over AD. These metabolic measures may become biomarkers identifying at-risk mothers and children for personalized interventions.

Metabolic adaptations to negative energy balance, as well as lipomobilization, influence inflammatory responses, immune function, and oxidative stress in animals. This study aimed to evaluate the biochemical profile of Mediterranean buffaloes with different levels of lipomobilization from the prepartum to the postpartum period. A total of 76 Mediterranean buffaloes were enrolled, and a weekly blood sample was taken from 7 weeks before to 6 weeks after calving. The concentration of non-esterified fatty acids (NEFAs) was determined in serum and was used to categorize buffaloes into three lipomobilization groups 7 weeks before calving: mild (NEFA-I; NEFA ≤ 0.29 mEq/L; n = 18), medium (NEFA-II; 0.29 < NEFA < 0.57 mEq/L; n = 20), and severe (NEFA-III; NEFA ≥ 0.57 mEq/L; n = 38). Two-way repeated measures ANOVA was used to assess changes within and between the groups and over time. Significant differences were found in the concentration levels of NEFA, β-hydroxybutyrate, glucose, cholesterol, protein profile, oxygen radicals, antioxidants, lysozyme, complement, and minerals. These results suggest that both medium and severe lipomobilization groups are associated with metabolic alterations. In conclusion, buffaloes with higher NEFA levels (>0.29 mEq/L; NEFA-II and NEFA-III) at 7 weeks before calving should be monitored more closely to reduce the risk of metabolic diseases. Furthermore, the medium (NEFA-II) and severe (NEFA-III) lipomobilization groups could be associated with differences in the animals\' ability to manage their metabolic status. Specifically, the severe mobilization group was most associated with a greater energy deficit during both the prepartum and postpartum periods without oxidative stress. On the contrary, the medium mobilization group was associated with a less severe energy deficit but was also associated with an inflammatory status and oxidative stress during the prepartum period. These distinctions highlight the need for tailored management strategies to address varying levels of metabolic stress in dairy buffaloes.

Metabolic changes are critical in the regulation of Ca2+ influx in central and peripheral neuroendocrine cells. To study the regulation of L-type Ca2+ channels by AMPK we used biochemical reagents and ATP/glucose-concentration manipulations in rat chromaffin cells. AICAR and Compound-C, at low concentration, significantly induce changes in L-type Ca2+ channel-current amplitude and voltage dependence. Remarkably, an overlasting decrease in the channel-current density can be induced by lowering the intracellular level of ATP. Accordingly, Ca2+ channel-current density gradually diminishes by decreasing the extracellular glucose concentration. By using immunofluorescence, a decrease in the expression of CaV1.2 is observed while decreasing extracellular glucose, suggesting that AMPK reduces the number of functional Ca2+ channels into the plasma membrane. Together, these results support for the first time the dependence of metabolic changes in the maintenance of Ca2+ channel-current by AMPK. They reveal a key step in Ca2+ influx in secretory cells.

Excess adipose tissue, as well as its distribution, correlates strongly with disorders of lipid and liver parameters and chronic inflammation. The pathophysiology of metabolic diseases caused by obesity is associated with the dysfunction of visceral adipose tissue. Effective and alternative interventions such as the Bioenteric Intragastric Balloon and bariatric surgeries such as the Roux-en-Y gastric bypass. The aim of this study was to assess the effect of modifying the recommended standard weight loss diet after bariatric surgery and procedures on reducing chronic inflammation in overweight patients. In the study, bioactive anti-inflammatory dietary components were used supportively. Changes in the concentrations of lipid parameters, liver parameters, antioxidant enzymes, cytokines, and chemokines were demonstrated. The enrichment of the diet, after bariatric surgery, with the addition of n-3 EFAs(Essential Fatty Acids), bioflavonoids, vitamins, and synbiotics resulted in higher weight losses in the patients in the study with a simultaneous reduction in parameters indicating liver dysfunction.

Metabolic reprogramming has been investigated in haematological malignancies. To date, a few studies have analysed the metabolic profile of paroxysmal nocturnal haemoglobinuria (PNH). The study by Chen and colleagues sheds light on the involvement of metabolic changes in the proliferation of PNH clones. Commentary on: Chen et al. The histone demethylase JMJD1C regulates CPS1 expression and promotes the proliferation of PNH clones through cell metabolic reprogramming. Br J Haematol 2024;204:2468-2479.

BACKGROUND: Use of levonorgestrel-releasing intrauterine device (LNG-IUD) has become common irrespective of age and parity. To date, only a few studies have examined its possible metabolic changes and large-scale biomarker profiles in detail and in a longitudinal design.
OBJECTIVE: To apply the metabolomics technique to examine the metabolic profile associated with the use of LNG-IUD both in a cross-sectional and in a longitudinal design.
METHODS: The study consists of cross-sectional and longitudinal analyses of a population-based survey (Health 2000) and its 11-year follow-up (Health 2011). All participants aged 18-49 years with available information on hormonal contraceptive use and metabolomics data (n=1767) were included. Altogether 212 metabolic measures in LNG-IUD users (n=341) were compared to those in non-users of hormonal contraception (n=1426) via multivariable linear regression models. Participants with complete longitudinal information (n=240) were divided into continuers, stoppers, starters, and never-user groups, and 11-year changes in levels of each metabolite were compared.
RESULTS: After adjustment for covariates, levels of 102 metabolites differed in LNG-IUD current users compared to non-users of hormonal contraception (median difference in biomarker concentration: -0.12 SD): lower levels of fatty acids concentrations and ratios, cholesterol, triglycerides and other lipids, as well as particle concentration, cholesterol, total lipids and phospholipids in lipoproteins. The 11-year metabolic changes did not differ in relation to changes in LNG-IUD use.
CONCLUSIONS: The use of LNG-IUD was associated with several moderate metabolic changes, mostly suggestive of a reduced arterial cardiometabolic risk. Changes in LNG-IUD use were not related to long-term metabolic changes.

This study evaluated effects of high starch (20%) on hematological variations, glucose and lipid metabolism, antioxidant ability, inflammatory responses, and histopathological lesions in largemouth bass. Results showed hepatic crude lipid and triacylglycerol (TAG) contents were notably increased in fish fed high starch. High starch could increase counts of neutrophils, lymphocytes, monocytes, eosinophils, and basophils and serum contents of TAG, TBA, BUN, and LEP (p < 0.05). There were increasing trends in levels of GLUT2, glycolysis, gluconeogenesis, and LDH in fish fed high starch through the AKT/PI3K signal pathway. Meanwhile, high starch not only triggered TAG and cholesterol synthesis, but mediated cholesterol accumulation by reducing ABCG5, ABCG8, and NPC1L1. Significant increases in lipid droplets and vacuolization were also shown in hepatocytes of D3-D7 groups fed high starch. In addition, high starch could decrease levels of mitochondrial Trx2, TrxR2, and Prx3, while increasing ROS contents. Moreover, high starch could notably increase amounts of inflammatory factors (IL-1β, TNF-α, etc.) by activating NLRP3 inflammasome key molecules (GSDME, caspase 1, etc.). In conclusion, high starch could not only induce metabolic disorders via gluconeogenesis and accumulation of glycogen, TAG, and cholesterol, but could disturb redox homeostasis and cause inflammatory responses by activating the NLRP3 inflammasome in largemouth bass.

Mitochondrial dysfunction is a significant feature of type 2 diabetes. MOTS-C, a peptide derived from mitochondria, has positive effects on metabolism and exercise capacity. This study explored the impact of high and moderate-intensity interval exercises on mitochondrial MOTS-C alterations and their correlation with metabolic markers in male diabetic sand rats. Thirty male sand rats were divided into six groups: control, MIIT, DM + HIIT, DM + MIIT, DM, and HIIT (5 rats each). Diabetes was induced using a high-fat diet (HFD) combined with streptozotocin (STZ). The Wistar sand rats in exercise groups underwent 8 weeks of interval training of varying intensities. Post sample collection, protein expressions of PCG-1a, AMPK, and GLUT4 were assessed through Western blot analysis, while MOTS-C protein expression was determined using ELISA. Both exercise intensity and diabetes significantly affected the levels of PCG-1a, MOTS-C, GLUT4 proteins, and insulin resistance (p < 0.001). The combined effect of diabetes status and exercise intensity on these levels was also significant (p < 0.001). However, the diabetes effect varied when comparing high-intensity to moderate-intensity exercise. The moderate-intensity exercise group with diabetes showed higher levels of PCG-1a, MOTS-C, and GLUT4 proteins and reduced insulin resistance levels (p < 0.001). Exercise intensity (p = 0.022) and diabetes (p = 0.008) significantly influenced AMPK protein levels. The interplay between diabetes status and exercise intensity on AMPK protein levels was noteworthy, with the moderate-intensity diabetes group exhibiting higher AMPK levels than the high-intensity diabetes group (p < 0.001). In conclusion, exercise elevates the levels of PCG-1a, MOTS-C, GLUT4, and AMPK proteins, regulating insulin resistance in diabetic sand rats. Given the AMPK-MOTS-C mitochondrial pathway\'s mechanisms, interval exercises might enhance the metabolic rates and general health of diabetic rodents.

This controlled study investigated metabolic changes in non-vaccinated individuals with Long-COVID-19, along with their connection to the severity of the disease. The study involved 88 patients who experienced varying levels of initial disease severity (mild, moderate, and severe), and a control group of 29 healthy individuals. Metabolic risk markers from fasting blood samples were analyzed, and data regarding disease severity indicators were collected. Findings indicated significant metabolic shifts in severe Long-COVID-19 cases, mainly a marked drop in HDL-C levels and a doubled increase in ferritin levels and insulin resistance compared to the mild cases and controls. HDL-C and ferritin were identified as the leading factors predicted by disease severity. In conclusion, the decline in HDL-C levels and rise in ferritin levels seen in Long-COVID-19 individuals, largely influenced by the severity of the initial infection, could potentially play a role in the persistence and progression of Long-COVID-19. Hence, these markers could be considered as possible therapeutic targets, and help shape preventive strategies to reduce the long-term impacts of the disease.

Fibroblast-like synoviocytes (FLS) are important components of the synovial membrane. They can contribute to joint damage through crosstalk with inflammatory cells and direct actions on tissue damage pathways in rheumatoid arthritis (RA). Recent evidence suggests that, compared with FLS in normal synovial tissue, FLS in RA synovial tissue exhibits significant differences in metabolism. Recent metabolomic studies have demonstrated that metabolic changes, including those in glucose, lipid, and amino acid metabolism, exist before synovitis onset. These changes may be a result of increased biosynthesis and energy requirements during the early phases of the disease. Activated T cells and some cytokines contribute to the conversion of FLS into cells with metabolic abnormalities and pro-inflammatory phenotypes. This conversion may be one of the potential mechanisms behind altered FLS metabolism. Targeting metabolism can inhibit FLS proliferation, providing relief to patients with RA. In this review, we aimed to summarize the evidence of metabolic changes in FLS in RA, analyze the mechanisms of these metabolic alterations, and assess their effect on RA phenotype. Finally, we aimed to summarize the advances and challenges faced in targeting FLS metabolism as a promising therapeutic strategy for RA in the future.