Metabolic Dysfunction-Associated Steatotic Liver Disease in Severe Obesity and Concordance Between Invasive (Biopsy) and Non-Invasive (OWLiver®) Diagnoses.

INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD), now termed metabolic dysfunction-associated steatotic liver disease (MASLD), is an escalating health concern linked to obesity and type 2 diabetes. Despite liver biopsy being the gold standard, its invasiveness underscores the need for non-invasive diagnostic methods. METHODS: A cross-sectional study was performed to assess MASLD using the non-invasive OWLiver® serum lipidomics test in a cohort of 117 patients with severe obesity undergoing bariatric surgery, comparing outcomes with liver biopsy. Exclusions (n = 24) included insufficient data, liver disease etiology other than MASLD, corticosteroid treatment, excessive alcohol consumption, low glomerular filtration rate and declination to participate. Comprehensive laboratory tests, demographic assessments and liver biopsies were performed. Serum metabolites were analyzed using OWLiver®, a serum lipidomic test that discriminates between healthy liver, steatosis, metabolic dysfunction-associated steatohepatitis (MASH) and MASH with fibrosis ≥2 by means of three algorithms run sequentially. RESULTS: Liver biopsy revealed a MASLD prevalence of 95.7%, with MASH present in 28.2% of cases. OWLiver® demonstrated a tendency to diagnose more severe cases. Body mass index (BMI), rather than the presence of type 2 diabetes, emerged as the sole independent factor linked to the probability of concordance. Therefore, the all-population concordance of 63.2% between OWLiver® and liver biopsy notably raised to 77.1% in patients with a BMI <40 kg/m². These findings suggest a potential correlation between lower BMI and enhanced concordance between OWLiver® and biopsy. CONCLUSION: This study yields valuable insights into the concordance between liver biopsy and the non-invasive serum lipidomic test, OWLiver®, in severe obesity. OWLiver® demonstrated a tendency to amplify MASLD severity, with BMI values influencing concordance. Patients with BMI < 40 kg/m² may derive optimal benefits from this non-invasive diagnostic approach.

Mid-term Effects of Bariatric Surgery on Metabolic Dysfunction-Associated Fatty Liver Disease Remission and Predictive Factors: A Prospective Study with a Focus on Non-invasive Diagnosis.

PURPOSE: Non-alcoholic fatty liver disease (NAFLD), now termed metabolic dysfunction-associated fatty liver disease (MAFLD), is a growing health concern associated with obesity and type 2 diabetes. Bariatric surgery offers potential benefits, but its impact on MAFLD remains incompletely understood, with scarce long-term follow-up prospective studies. Moreover, being liver biopsy the gold standard for liver condition measurement, the need for non-invasive techniques that allow the assessment of MAFLD development after bariatric surgery is imperative. OWLiver® Care and OWLiver® represent two serum lipidomic tests, featuring panels comprising 11 and 20 triglycerides, respectively. MATERIALS AND METHODS: We conducted a prospective study involving 80 Caucasians to assess the effects of bariatric surgery on MAFLD using non-invasive diagnostics and to identify baseline predictors of MAFLD remission. Serum samples were collected before surgery and at a 3-year follow-up. RESULTS: After 3 years, the proportion of patients exhibiting a healthy liver escalated from 5.0% at baseline to 26.3%. Conversely, the percentage of steatohepatitis declined from 35.1% to a mere 7.6%. Younger age, female gender, and the absence of type 2 diabetes were associated with MAFLD remission. However, age stood as the only independent variable associated with this favorable liver evolution (R2 = 0.112). CONCLUSION: Bariatric surgery demonstrates mid-term benefits in improving MAFLD, with younger age as a baseline predictor of remission. Non-invasive diagnostic methods, like OWLiver®, are valuable tools for monitoring MAFLD evolution. Further research with larger populations and longer follow-up periods is warranted to refine personalized treatment approaches.

Proanthocyanidins Restore the Metabolic Diurnal Rhythm of Subcutaneous White Adipose Tissue According to Time-Of-Day Consumption.

Consumption of grape seed proanthocyanidin extract (GSPE) has beneficial effects on the functionality of white adipose tissue (WAT). However, although WAT metabolism shows a clear diurnal rhythm, whether GSPE consumption could affect WAT rhythmicity in a time-dependent manner has not been studied. Ninety-six male Fischer rats were fed standard (STD, two groups) or cafeteria (CAF, four groups) diet for 9 weeks (n = 16 each group). From week 6 on, CAF diet animals were supplemented with vehicle or 25 mg GSPE/kg of body weight either at the beginning of the light/rest phase (ZT0) or at the beginning of the dark/active phase (ZT12). The two STD groups were also supplemented with vehicle at ZT0 or ZT12. In week 9, animals were sacrificed at 6 h intervals (n = 4) to analyze the diurnal rhythms of subcutaneous WAT metabolites by nuclear magnetic resonance spectrometry. A total of 45 metabolites were detected, 19 of which presented diurnal rhythms in the STD groups. Although most metabolites became arrhythmic under CAF diet, GSPE consumption at ZT12, but not at ZT0, restored the rhythmicity of 12 metabolites including compounds involved in alanine, aspartate, and glutamate metabolism. These results demonstrate that timed GSPE supplementation may restore, at least partially, the functional dynamics of WAT when it is consumed at the beginning of the active phase. This study opens an innovative strategy for time-dependent polyphenol treatment in obesity and metabolic diseases.

Time-of-day dependent effect of proanthocyanidins on adipose tissue metabolism in rats with diet-induced obesity.

BACKGROUND: Grape-seed proanthocyanidin extract (GSPE) improve white adipose tissue (WAT) expansion during diet-induced obesity. However, because adipose metabolism is synchronized by circadian rhythms, it is plausible to speculate that the bioactivity of dietary proanthocyanidins could be influenced by the time-of-day in which they are consumed. Therefore, the aim of the present study was to determine the interaction between zeitgeber time (ZT) and GSPE consumption on the functionality of WAT in rats with diet-induced obesity. METHODS: Male Wistar rats were fed a cafeteria diet for 9 weeks. After 5 weeks, the animals were supplemented with 25 mg GSPE/kg for 4 weeks at the beginning of the light/rest phase (ZT0) or of the dark/active phase (ZT12). Body fat content was determined by nuclear magnetic resonance and histological analyses were performed in the epididymal (EWAT) and inguinal (IWAT) fat depots to determine adipocyte size and number. In addition, the expression of genes related to adipose metabolism and circadian clock function were analyzed by qPCR. RESULTS: GSPE consumption at ZT0 was associated with a potential antidiabetic effect without affecting adiposity and energy intake and downregulating the gene expression of inflammatory markers in EWAT. In contrast, GSPE consumption at ZT12 improved adipose tissue expansion decreasing adipocyte size in IWAT. In accordance with this adipogenic activity, the expression of genes involved in fatty acid metabolism were downregulated at ZT12 in IWAT. In turn, GSPE consumption at ZT12, but not at ZT0, repressed the expression of the clock gene Cry1 in IWAT. CONCLUSIONS: The interaction between ZT and GSPE consumption influenced the metabolic response of WAT in a tissue-specific manner. Understanding the impact of circadian clock on adipose metabolism and how this is regulated by polyphenols will provide new insights for the management of obesity.

Supplementation with a Specific Combination of Metabolic Cofactors Ameliorates Non-Alcoholic Fatty Liver Disease, Hepatic Fibrosis, and Insulin Resistance in Mice.

Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) have emerged as the leading causes of chronic liver disease in the world. Obesity, insulin resistance, and dyslipidemia are multifactorial risk factors strongly associated with NAFLD/NASH. Here, a specific combination of metabolic cofactors (a multi-ingredient; MI) containing precursors of glutathione (GSH) and nicotinamide adenine dinucleotide (NAD+) (betaine, N-acetyl-cysteine, L-carnitine and nicotinamide riboside) was evaluated as effective treatment for the NAFLD/NASH pathophysiology. Six-week-old male mice were randomly divided into control diet animals and animals exposed to a high fat and high fructose/sucrose diet to induce NAFLD. After 16 weeks, diet-induced NAFLD mice were distributed into two groups, treated with the vehicle (HFHFr group) or with a combination of metabolic cofactors (MI group) for 4 additional weeks, and blood and liver were obtained from all animals for biochemical, histological, and molecular analysis. The MI treatment reduced liver steatosis, decreasing liver weight and hepatic lipid content, and liver injury, as evidenced by a pronounced decrease in serum levels of liver transaminases. Moreover, animals supplemented with the MI cocktail showed a reduction in the gene expression of some proinflammatory cytokines when compared with their HFHFr counterparts. In addition, MI supplementation was effective in decreasing hepatic fibrosis and improving insulin sensitivity, as observed by histological analysis, as well as a reduction in fibrotic gene expression (Col1α1) and improved Akt activation, respectively. Taken together, supplementation with this specific combination of metabolic cofactors ameliorates several features of NAFLD, highlighting this treatment as a potential efficient therapy against this disease in humans.