Dietary timing enhances exercise by modulating fat-muscle crosstalk via adipocyte AMPKα2 signaling.

Feeding rhythms regulate exercise performance and muscle energy metabolism. However, the mechanisms regulating adipocyte functions remain unclear. Here, using multi-omics analyses, involving (phospho-)proteomics and lipidomics, we found that day-restricted feeding (DRF) regulates diurnal rhythms of the mitochondrial proteome, neutral lipidome, and nutrient-sensing pathways in mouse gonadal white adipose tissue (GWAT).

SR-A3 suppresses AKT activation to protect against MAFLD by inhibiting XIAP-mediated PTEN degradation.

Scavenger receptor class A member 3 (SR-A3) is implicated in metabolic diseases; however, the relationship between SR-A3 and metabolic dysfunction-associated fatty liver disease (MAFLD) has not been documented. Here, we show that hepatic SR-A3 expression is significantly reduced in human and animal models in the context of MAFLD. Genetic inhibition of SR-A3 in hamsters elicits hyperlipidemia, hyperglycemia, insulin resistance, and hepatic steatosis under chow-diet condition, yet escalates in diet-induced MAFLD.

Fat-1 Ameliorates Metabolic Dysfunction-Associated Fatty Liver Disease and Atherosclerosis through Promoting the Nuclear Localization of PPARα in Hamsters.

Fat-1, an enzyme encoded by the gene, is responsible for the conversion of endogenous omega-6 polyunsaturated fatty acids into omega-3 polyunsaturated fatty acids in . To better investigate whether the expression of Fat-1 will exert a beneficial function in dyslipidemia and metabolic dysfunction-associated fatty liver disease (MAFLD), we established an adeno-associated virus 9 expressing Fat-1. We found that adeno-associated-virus-mediated expression of Fat-1 markedly reduced the levels of plasma triglycerides and total cholesterol but increased high-density lipoprotein levels in male wild-type hamsters on both chow diet and high-fat diet as well as in chow-diet-fed male LDLR hamsters.

Metformin alleviates sphingolipids dysregulation and improves obesity-related kidney disease in high-fat diet rats.

Obesity-related kidney disease (ORKD) has recently become a global health issue. Metformin is widely used in patients with type 2 diabetes with concomitant obesity, but its effects on ORKD are insufficiently understood. Accumulation of lipid species including sphingolipids has been reported to disrupt glomerular functions and drive progression of chronic kidney disease.

Multi-omics dissection of metabolic dysregulation associated with immune recovery in people living with HIV-1.

Background: Despite the success of antiretroviral therapy (ART) in suppressing HIV-1 replication, some people living with HIV-1 (PLWH) fail to achieve an optimal recovery of CD4 T cells, and precise metabolic regulation underlying immune recovery remained poorly understood.

Methods: In this cross-sectional study, mass spectrometry was used for quantitative analysis of plasma metabolome and lipidome in 24 treatment-naïve PLWH (TNs), 33 immunological responders (IRs), 35 immunological non-responders (INRs), and 16 healthy controls (HCs). The data were analyzed using the Mann-Whitney U-test, Kruskal-Wallis test, Spearman correlation, and LASSO regression analysis.

Long-chain acyl-CoA synthetase regulates systemic lipid homeostasis via glycosylation-dependent lipoprotein production.

Interorgan lipid transport is crucial for organism development and the maintenance of physiological function. Here, we demonstrate that long-chain acyl-CoA synthetase (dAcsl), which catalyzes the conversion of fatty acids into acyl-coenzyme As (acyl-CoAs), plays a critical role in regulating systemic lipid homeostasis. dAcsl deficiency in the fat body led to the ectopic accumulation of neutral lipids in the gut, along with significantly reduced lipoprotein contents in both the fat body and hemolymph.

Lithocholic acid phenocopies anti-ageing effects of calorie restriction.

Calorie restriction (CR) is a dietary intervention used to promote health and longevity. CR causes various metabolic changes in both the production and the circulation of metabolites; however, it remains unclear which altered metabolites account for the physiological benefits of CR. Here we use metabolomics to analyse metabolites that exhibit changes in abundance during CR and perform subsequent functional validation.

Non-invasive lipid panel of MASLD fibrosis transition underscores the role of lipoprotein sulfatides in hepatic immunomodulation.

There exists a pressing need for a non-invasive panel that differentiates mild fibrosis from non-fibrosis in metabolic dysfunction-associated steatotic liver disease (MASLD). In this work, we applied quantitative lipidomics and sterolomics on sera from the PERSONS cohort with biopsy-based histological assessment of liver pathology. We trained a lasso regression model using quantitative omics data and clinical variables, deriving a combinatorial panel of lipids and clinical indices that differentiates mild fibrosis (>F1, n = 324) from non-fibrosis (F0, n = 195), with an area under receiver operating characteristic curve (AUROC) at 0.

Spatial organization of PI3K-PI(3,4,5)P-AKT signaling by focal adhesions.

The class I phosphatidylinositol 3-kinase (PI3K)-AKT signaling pathway is a key regulator of cell survival, growth, and proliferation and is among the most frequently mutated pathways in cancer. However, where and how PI3K-AKT signaling is spatially activated and organized in mammalian cells remains poorly understood. Here, we identify focal adhesions (FAs) as subcellular signaling hubs organizing the activation of PI3K-PI(3,4,5)P-AKT signaling in human cancer cells containing p110α mutations under basal conditions.

Combinatorial lipidomics and proteomics underscore erythrocyte lipid membrane aberrations in the development of adverse cardio-cerebrovascular complications in maintenance hemodialysis patients.

Patients on maintenance hemodialysis exhibit a notably higher risk of cardio-cerebrovascular complications that constitute the major cause of death. Preceding studies have reported conflicting associations between traditional lipid measures and clinical outcome in dialysis patients. In this prospective longitudinal study, we utilized quantitative lipidomics to elucidate, at molecular resolution, changes in lipidome profiles of erythrocyte and plasma samples collected from maintenance hemodialysis patients followed up for 86 months (≈7 years).

Glut3 promotes cellular O-GlcNAcylation as a distinctive tumor-supportive feature in Treg cells.

Regulatory T cells (Tregs) establish dominant immune tolerance but obstruct tumor immune surveillance, warranting context-specific mechanistic insights into the functions of tumor-infiltrating Tregs (TIL-Tregs). We show that enhanced posttranslational O-linked N-acetylglucosamine modification (O-GlcNAcylation) of cellular factors is a molecular feature that promotes a tumor-specific gene expression signature and distinguishes TIL-Tregs from their systemic counterparts. We found that altered glucose utilization through the glucose transporter Glut3 is a major facilitator of this process.

Lipid droplets sequester palmitic acid to disrupt endothelial ciliation and exacerbate atherosclerosis in male mice.

Disruption of ciliary homeostasis in vascular endothelial cells has been implicated in the development of atherosclerosis. However, the molecular basis for the regulation of endothelial cilia during atherosclerosis remains poorly understood. Herein, we provide evidence in male mice that the accumulation of lipid droplets in vascular endothelial cells induces ciliary loss and contributes to atherosclerosis.

Cryo-EM structures of a mycobacterial ABC transporter that mediates rifampicin resistance.

Drug-resistant Tuberculosis (TB) is a global public health problem. Resistance to rifampicin, the most effective drug for TB treatment, is a major growing concern. The etiological agent, (), has a cluster of ATP-binding cassette (ABC) transporters which are responsible for drug resistance through active export.

TMEM16F Expressed in Kupffer Cells Regulates Liver Inflammation and Metabolism to Protect Against Listeria Monocytogenes.

Infection by bacteria leads to tissue damage and inflammation, which need to be tightly controlled by host mechanisms to avoid deleterious consequences. It is previously reported that TMEM16F, a calcium-activated lipid scramblase expressed in various immune cell types including T cells and neutrophils, is critical for the control of infection by bacterium Listeria monocytogenes (Lm) in vivo. This function correlated with the capacity of TMEM16F to repair the plasma membrane (PM) damage induced in T cells in vitro, by the Lm toxin listeriolysin O (LLO).

Lipidomics and metabolomics investigation into the effect of DAG dietary intervention on hyperuricemia in athletes.

The occurrence of hyperuricemia (HUA; elevated serum uric acid) in athletes is relatively high despite that exercise can potentially reduce the risk of developing this condition. Although recent studies have shown the beneficial properties of DAG in improving overall metabolic profiles, a comprehensive understanding of the effect of DAG in modulating HUA in athletes is still lacking. In this study, we leveraged combinatorial lipidomics and metabolomics to investigate the effect of replacing TAG with DAG in the diet of athletes with HUA.

Golgi protein ACBD3 downregulation sensitizes cells to ferroptosis.

Ferroptosis, a form of cell death driven by iron-dependent lipid peroxidation, is emerging as a promising target in cancer therapy. It is regulated by a network of molecules and pathways that modulate lipid metabolism, iron homeostasis and redox balance, and related processes. However, there are still numerous regulatory molecules intricately involved in ferroptosis that remain to be identified.

Erratum to "Lipidome Atlas of the Developing Heart Uncovers Dynamic Membrane Lipid Attributes Underlying Cardiac Structural and Metabolic Maturation".

[This corrects the article DOI: 10.34133/research.0006.