Alleviation of adverse effects associated with α-glucosidase inhibitors by Ocimum basilicum L., Matricaria chamomilla L., and Salvia officinalis L. reveals novel selective inhibition of Bacillus α-glucosidase by acarbose.

Hepatoprotective effects of tetrahydropalmatine against NAFLD through autophagy activation and lipid metabolic reprogramming via the AMPK-mTOR-Sirt1 axis.

Toward anti-bluing shift: A rationally designed photo-induced electron transfer-based polarity responsive lipid droplets-targeting fluorescent probe for real-time monitoring of drug-induced liver injury.

A lipidomics approach identifies the lipid classes modulated in response to hepatic steatosis in obese fa/fa rats relative to lean Zucker rats.

Promoter demethylation and protein O-GlcNAcylation-mediated enhancement of fatty acid synthase contributes to hepatic steatosis and inflammation in MASLD.

Saroglitazar magnesium, a dual PPAR α/γ agonist, is approved in India for the treatment of non-alcoholic fatty liver disease (NAFLD), now known as metabolic dysfunction-associated steatotic liver disease (MASLD). While controlled trials with saroglitazar have demonstrated improvements in hepatic and metabolic parameters in patients with MASLD, real-world data in populations with diverse metabolic comorbidities remain limited. This is an ongoing, prospective, single-arm, multicenter, real-world, phase 4 study evaluating the effectiveness and safety of saroglitazar 4 mg once daily in patients with MASLD. The current interim analysis includes 500 patients who completed 24 weeks of treatment. Changes in liver stiffness measurement (LSM), hepatic steatosis (CAP and UAP), glycemic control, lipid profile, liver enzymes and non-invasive fibrosis scores were assessed. Safety was evaluated based on treatment-emergent adverse events (TEAEs). This was a non-protocol-defined, exploratory interim analysis; all statistical inferences are descriptive and p-values are nominal. At baseline, the mean age was 45.7 ± 11.6 years, weight 81.0 ± 13.6 kg, body mass index (BMI) 29.9 ± 4.7 kg/m2 and 42% had obesity. After 24 weeks of treatment, mean LSM ± SD decreased from 10.1 ± 3.2 kPa to 8.0 ± 3.2 kPa (-20.7%, p < 0.001) and CAP decreased by 20.3 dB/m (p < 0.001). ALT levels reduced by 33.6% (p < 0.001) and HbA1c by 4.8% (p < 0.001). Improvements were also observed in lipid profile and fibrosis scores (FIB-4, FAST, APRI, ALERT). A total of 68 patients (13.6%) reported TEAEs, the majority of which were mild (85.5%) and unrelated to the study drug. No deaths were reported. In this interim real-world analysis, saroglitazar 4 mg was associated with improvements in liver stiffness, hepatic steatosis, metabolic parameters and non-invasive fibrosis markers in patients with MASLD. The treatment was generally well tolerated. These findings warrant further confirmation upon completion of the 52-week analysis. Saroglitazar 4 mg for 24 weeks was associated with improvements in surrogate markers of liver injury, steatosis, glycaemic control and lipid metabolism, with good tolerability. These interim real-world findings support further evaluation in the planned 52-week analysis. CTRI/2023/05/053326 [Registered on: 31/05/2023].

Metabolic dysfunction-associated fatty liver disease (MAFLD), recently redefined from non-alcoholic fatty liver disease (NAFLD), highlights the central role of metabolic dysfunction in its pathophysiology. The L-α-lysophosphatidylinositol/G protein-coupled receptor 55 (LPI/GPR55) axis, an element of the endocannabinoidome, has emerged as a key driver behind liver disease progression, leading to the progression of metabolic dysfunction associated steatohepatitis (MASH). Implicated in hepatic lipid accumulation, inflammation and fibrosis, this axis has detrimental effects in hepatocytes, Kupffer cells and hepatic stellate cells. Furthermore, recent evidence suggests that this axis induces de novo lipogenesis, promoting pro-inflammatory cytokine production, leading to fibrosis and the transition toward a steatotic liver. The enzyme membrane-bound O-acyltransferase domain-containing 7 (MBOAT7) modulates this axis by acylation of LPI, exacerbating hepatic steatosis and insulin resistance. Until recently, no pharmacologic treatments were approved for MAFLD. However, resmetirom received FDA approval in March 2024 for the treatment of MASH, and semaglutide (Wegovy) was granted accelerated FDA approval in August 2025 for MASH with moderate-to-advanced fibrosis. Additional agents such as tirzepatide and retatrutide remain in late-stage clinical development. We propose that targeting the endocannabinoidome, specifically the LPI/GPR55 axis, represents a promising therapeutic strategy for liver disease. Previous attempts to target GPR55 therapeutically have involved small-molecule agonists and phytocannabinoids with antagonistic activity. However, progress remains limited due to the context-specific roles of GPR55 across different tissues and signalling pathways. As such, future strategies involving the LPI/GPR55 axis must focus on hepatic-specific GPR55 modulation using selective ligands and advanced delivery systems, mitigating off-target effects. This review elucidates the mechanistic role of the LPI/GPR55 axis, combining the role of MBOAT7 in the pathophysiology of metabolic-associated liver disease.

SLC13 sodium-carboxylate transporters: function, regulation and pathophysiological implications in human disease.

Consumers' risky eating behaviours aided by the current food environment have led to an increase in diet-related metabolic disorders. Metabolic (dysfunction)-associated fatty liver disease origin represents a major global health burden that is increasing at an alarming rate on an annual basis. Modifying the timing of calorie consumption, dietary composition, or caloric intake offers a promising therapeutic approach for the management of this condition. The aim of this review was to provide a concise analysis of the impact of intermittent fasting on the regulation of glucocorticoid levels and diet-induced metabolic disorders with a focus on non-alcoholic fatty liver diseases. We found that intermittent fasting primarily regulates hepatic autophagy via nutritional and hormonal pathways, aiding in the maintenance of energy equilibrium, enhancement of mitochondrial function, regulation of liver quality, preservation of cellular homeostasis, protection of cells from harmful factors, mitigation of liver metabolic disorders, and improvement of liver inflammation. Also, the physiological changes induced by intermittent fasting and their metabolic consequences arise through multiple mechanisms, including alterations in hepatic metabolism, hepatic autophagy, inflammatory responses, liver functional enzymes, hepatic steatosis, fibroblast growth factor signalling, White adipoe tissue browning, adipokines, circadian rhythms, lipid profiles, body composition, the adipose tissue-gut microbiome axis, skeletal muscle, and the autophagy process. Interestingly, we identified the complex interplay among glucocorticoids, intermittent fasting, and non-alcoholic fatty liver diseases highlighting the hepatic macrophage glucocorticoid receptor as a pivotal mediator of fasting-induced reprogramming of the macrophage secretome, including fasting-suppressed cytokines. In conclusion, existing data indicates that intermittent fasting in patients with non-alcoholic fatty liver diseases is a viable, safe, and successful strategy for weight reduction, demonstrating notable trends in the amelioration of dyslipidaemia and non-alcoholic fatty liver diseases.

A pulse-echo sound speed estimation approach with prior constraints for layered media.

Hypertriglyceridemia (HTG) is an independent risk factor for atherosclerotic cardiovascular disease (ASCVD) and acute pancreatitis (AP). Early detection and treatment are important to prevent such complications. This review briefly outlines the etiology and novel treatments of HTG and recent findings from contemporary HTG registries. HTG is associated with an increased prevalence of cardiometabolic risk factors, including obesity, diabetes, and hepatic steatosis. Novel ribonucleic acid-based treatments for HTG have shown a substantial reduction in plasma triglycerides and a lower incidence of AP. A recent trial confirmed such benefit in patients with triglycerides >500 mg/dl (5.6 mmol/l), albeit with an increase in low-density lipoprotein-cholesterol, a reduction in remnant cholesterol and no change in apolipoprotein B. There is a need to harmonize the definitions of HTG and improve the care of individuals with severe HTG and familial chylomicronemia syndrome. New and evolving international registries are beginning to provide useful real-world data. Patient registries for HTG have provided valuable data for understanding the link between HTG and other cardiometabolic disorders; they can inform the planning of clinical services and the translation of the findings of new and future clinical trials of triglyceride-lowering therapies.

1-O-acetylbritannilactone alleviates high-fat diet-induced fatty liver by covalently targeting NLRP3.

Risk-associated and clinically informative biomarkers for cardiovascular risk stratification in metabolic dysfunction-Associated steatotic liver disease.

Integrative functional genomics and fine-mapping identify regulatory mechanisms of multivariate obesity GWAS and its cardiometabolic implications.

Puerarin from Pueraria montana var. lobata (Willd.) alleviates hepatic steatosis and inflammation in MAFLD through suppressing STING-IRF3/NF-κB signaling in macrophages.

Time-restricted feeding (TRF), which confines food intake to specific time periods without altering nutrient content or reducing calories, has shown promise in improving cardiometabolic health. This study tested whether a 2-wk TRF intervention during the active (dark) period could reverse long-term effects of a high-fat diet (HFD) on liver mitochondrial function, steatosis, and metabolism in mice. Male C57BL/6J mice were fed either a normal-fat diet (NFD, 10% kcal fat) or an HFD (45% kcal fat) ad libitum for 18 wk, followed by 2 wk of active period TRF. Assessments included whole body metabolism, gene expression, histopathology, plasma lipid levels, and mitochondrial bioenergetic function. Chronic HFD feeding abolished the day-night difference in the respiratory exchange ratio (RER), altered 24-h expression rhythms of clock, lipid, and mitochondrial metabolism genes in the liver, and eliminated diurnal variation in liver mitochondrial bioenergetics. TRF partially restored RER rhythmicity without altering body composition or reducing caloric intake in HFD mice. TRF also reset 24-h expression rhythms in clock and several metabolic genes, normalized liver and plasma triglyceride oscillations, and reduced small droplet macrosteatosis in the livers of HFD mice. Importantly, TRF improved liver mitochondrial respiration and reduced circulating levels of mitochondrial transcription factor A, a mitochondrially-derived damage-associated molecule pattern, indicating reduced mitochondrial injury in HFD mice. These findings suggest that TRF can rapidly reverse HFD-induced disruptions in metabolic and mitochondrial function, offering a promising new nonpharmacologic strategy for improving liver health in obesity-related metabolic disease.

Productive and morphological responses of japanese quails (Coturnix japonica) supplemented with phytase superdosing at different temperatures.

Aloesin improves metabolic associated fatty liver disease and obesity by targeting TGFBR1.

Lipid droplet-specific fluorescent biosensor based on triphenylamine derivatives for the diagnosis of non-alcoholic fatty liver disease (NAFLD) at varying stages.

Natural polyketide enterocin inhibits ASGR1 to enhance cholesterol efflux and regulate hepatic lipid metabolism.