Carbendazim disrupts cellular lipid homeostasis and induces fat accumulation by upregulation of Δ9-desaturases in Caenorhabditis elegans.

m6preQ0 reduces oxidative stress and alleviates glucose-induced lipid accumulation via insulin/IGF-1 signaling pathway in C. elegans.

Extensive evidence indicates that lipid accumulation causes renal tubular injury, which further contributes to diabetic nephropathy (DN) progression. Short-chain fatty acids (SCFAs) play an important role in the maintenance of cellular metabolic health. Previous studies have found a significant deficiency of SCFAs in DN patients, although their effectson lipid accumulation in renal tubules have not been investigated. We have investigated the effect of sodium butyrate (NaB), one of the most abundant SCFAs, on renal tubular lipid accumulation in DN and elucidated its underlying protective mechanisms. The effects of NaB were investigated on renal tubular lipid accumulation in vitro (using a glucolipotoxicity-treated HK-2 cell line) and DN progression in vivo (with streptozotocin injection combined with a high-fat diet in C57BL/6J mice). RNA sequencing, surface plasmon resonance, pulldown MS assay, and molecular docking were applied to explore specific molecular mechanisms. Our findings revealed that serum butyrate levels were reduced in DN patients and inversely correlated with DN severity. NaB supplementation improved renal tubular lipid accumulation and injury in HK-2 cells and DN mice. The protective effects of NaB were largely abrogated in kidney-specific Tfeb knockout mice. NaB directly interacted with PPP2R1A to promote the formation and activation of PP2A heterotrimers, thereby facilitating the dephosphorylation of TFEB and promoting lipophagy. NaB functions as a PP2A-TFEB axis activator to restore lipophagy and ameliorate lipid accumulation in tubular epithelial cells, pointing to NaB as a promising protective agent against renal injury in DN patients.

CYR61 promotes obesity-induced kidney injury by activating endoplasmic reticulum stress.

Triclosan (TCS) is an antimicrobial toxicant found in a wide range of consumer products and has been detected in human tissues at concentrations ranging from 0.001 to 5 ppm. Hepatotoxic chemicals such as TCS can cause steatotic liver disease, a condition referred to as toxicant-associated steatotic liver disease. Once TCS enters the body, it induces liver UDP-glucuronosyltransferase (UGT) 1A proteins, leading to the formation of TCS glucuronides, which are biologically inactive metabolites. The induction of UGT1A proteins by TCS is regulated by the nuclear receptor peroxisome proliferator-activated receptor α (PPARα). In this study, we evaluated the impact of TCS on the PPARα-UGT1 axis in steatohepatitis and hepatocellular carcinoma using humanized UGT1 (hUGT1) male mice. We have demonstrated that TCS exposure promotes liver tumorigenesis and induces human UGT1A1 and other human UGT1A proteins in the liver. Furthermore, our results demonstrate that UGT1A gene induction in the liver is dependent on PPARα. When PPARα-deficient hUGT1 mice (hUGT1/Pparα-/-) were exposed to TCS for 5 months, steatohepatitis was exacerbated, accompanied by increased fibrosis, immune cell infiltration, lipid accumulation, and hepatocyte ballooning. Finally, we assessed whether disruption of the PPARα-UGT1 axis contributes to liver tumorigenesis. Our data indicate that deletion of PPARα and consequent impairment of UGT1A gene induction in the liver have no effect on tumor progression and malignancy. Our hUGT1/Pparα-/- mouse model was a suitable model to study the TCS metabolism and how ablation of UGT1A proteins worsens TCS-induced metabolic dysfunction-associated steatohepatitis. SIGNIFICANCE STATEMENT: Triclosan strongly induces hepatic UGT1A gene expression through a PPARα-dependent mechanism in humanized UGT1 (hUGT1) mice. Loss of PPARα in hUGT1 mice augments triclosan-induced steatohepatitis, characterized by increased fibrosis, lipid accumulation, immune cell infiltration, and hepatocyte ballooning.

Macrophage METTL3 synergizes with YTHDF2 to promote atherosclerosis by inhibiting the LXR-α/ABCA1 pathway.

Caveolin-1 regulates cellular cholesterol homeostasis and its potential as an atherosclerosis therapy target.

In obesity, adipose tissue (AT) macrophages (ATMs) reprogram their metabolism to influence AT remodeling and function. Ubiquitin (Ub) ligases are critical in modulating the degradation of key proteins implicated in macrophage lipid metabolism. Yet, the role of Ub ligases in ATM lipid metabolism is largely unexplored. Previously, we reported that the Ub ligase Siah2 (seven in absentia homolog 2) is crucial in mediating adipogenic pathways and AT inflammation. Here, we cocultured bone marrow-derived macrophages with AT as an ex vivo model of bone marrow-derived ATMs to investigate the role of Siah2 in ATM lipid metabolism. We found that AT-induced lipid accumulation in ATMs was exacerbated by Siah2 deficiency via increased CD36-mediated lipid uptake and reduced lipid delivery to lysosomes. Together, these changes contributed to excessive lipid accumulation, lipid peroxidation, and an inflammatory phenotype. Our data reveal a central role for Siah2 as a lipid uptake sensor in maintaining the balance between lipid influx and degradation in ATMs.

Atherosclerosis is a highly complex and heterogeneous disease characterized by inflammation and lipid accumulation in the arterial wall. Genetic studies to identify loci and genes predisposing to the disease have now been carried out in large human cohorts and the underlying pathways have been studied in animal models, primarily mice. This review summarizes recent findings relating to genetic contributions to the disease and implications for diagnosis and treatment. Recent discoveries of genes contributing to all aspects of atherosclerosis and related diseases, including inflammation, lipid levels and oxidation, clonal hematopoiesis, hypertension, cardiac function, and aortic stenosis, are discussed. Altogether, several hundred contributing genes have been identified, and these are enabling a better understanding of the important pathways involved. These findings have also led to the development of improved diagnostic methods, including overall risk evaluation, and the identification of new therapeutic targets. Genetics is proving to be a powerful approach to dissecting atherosclerosis. Genetic studies promise to revolutionize the diagnosis and treatment of the disease.

Transcriptomic analysis of carbon flux redirection and lipid accumulation in the marine microalga Nannochloropsis granulata under nitrogen limitation

Amino-modified polystyrene nanoplastics induce endothelial pyroptosis and pro-atherogenic cellular responses.

STING-mediated metabolic reprogramming drives lipid peroxidation during Staphylococcus aureus infection.

• In stage I, nitrate boosted CO 2 fixation, pigments, photosynthesis, and biomass. • N 2 deprivation increased carbohydrates, lipids, and antioxidants in stage I. • In stage II, 4dN − maximized lipid (52.6%), neutral lipid (46.6%), and hydrocarbons. • CHNS showed higher HHV, CV, and TMP in 4dN − cultures. • FAME profiling showed dominant C16–C18 SFAs (32.65%), suiting biodiesel. Despite the promise of microalgal bioenergy, the trade-off between biomass production, lipid accumulation, and biodiesel yield under nutrient stress remains a key limitation. This study used M. contortum to assess the effects of nitrate supplementation on biomass yield (stage I) and of nitrate deprivation on lipid biosynthesis (stage II) using growth kinetics and metabolite profiling to harness bioenergy potential. During stage I, nitrate supplementation at 0.25 g L −1 enhanced growth, CO 2 fixation, biomass, pigments, photosynthetic efficiency (Fv/Fm, Y(II), α, Ik, and ETRmax), and protein content, whereas nitrate deprivation (0 g L −1 ) increased carbohydrate (3.6-fold) and lipid content (4.3-fold), along with elevated carotenoids, Y(NO), MDA, and antioxidant activities (CAT, APX, TFC, and TPC). In stage II, the 4-day nitrogen-deprived culture (4dN − ) achieved the highest lipid content (52.6%) and neutral lipid fraction (46.6%), along with the lowest glycolipid (9.5%) and phospholipid (7.1%) contents. Elevated lipid content was supported by FTIR peaks at 2920, 2852, and 1739 cm −1 , indicating metabolic reprogramming of M. contortum toward TAG accumulation and hydrocarbon synthesis. Additionally, CHNS analysis showed higher carbon and hydrogen, with lower nitrogen, sulfur, and oxygen, resulting in increased C/N and H/C ratios, HHV, CV, TMP, COD, and TEF in 4dN − cultures, indicating enhanced bioenergy potential. P-XRD analysis revealed an enhancement in the amorphous characteristics of the biomass. Furthermore, GC–MS analysis showed that SFAs (32.65%), mainly C16–C18, were predominant over MUFAs (18.08%) and PUFAs (23.11%) in 4dN − cultures. The resulting biodiesel met the EN 14214 and ASTM D6751 standards, highlighting M. contortum potential to achieve SDG 7.

Bisphenol analogs affected hepatic development and disrupted lipid homeostasis in zebrafish larvae.

METTL3-m6A-MALAT1 axis exacerbates the autophagy impairment and lipid accumulation in NAFLD by regulating miR-690.

Application of biphasic cultivation under the influence of nitrogen and light quality on biomass and lipid accumulation by Nostoc sp. CACIAM 21 for biofuel production

Rare earth element erbium induces hepatotoxicity in zebrafish.

Physicochemical characterization, lipid-metabolism effects and transcriptomics insights of perilla seed oil in high-fat-diet induced rats.

β-Nicotinamide mononucleotide prevents senescence and lipid accumulation in hepatic stellate cells by restoring SIRT1 function.

Demethyleneberberine alleviates cellular senescence of human fibroblasts by directly activating FEN1.