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.

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

INTRODUCTION: Nonalcoholic 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 noninvasive diagnostic methods. METHODS: A cross-sectional study was performed to assess MASLD using the noninvasive 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 noninvasive 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 noninvasive diagnostic approach.

Assessment of dyspneic sensation in patients with type 2 diabetes.

Introduction: Individuals with type 2 diabetes (T2D) should be considered a susceptible group for pulmonary dysfunction. So, we aimed to evaluate the sensation of breathlessness in this population by administering two well-validated questionnaires. Methods: This is a crosssectional study with 592 people without known respiratory disease (353 with T2D) who answered the modified Medical Research Council (mMRC) questionnaire. In addition, 47% also responded to the St George Respiratory Questionnaire, a specific instrument designed to be applied to patients with obstructive airway disease. Results: Patients with T2D showed a higher mMRC score in comparison to the control group [1.0 (0.0 - 4.0) vs. 0.0 (0.0 - 4.0), p<0.001]. A higher prevalence of subjects with mMRC ≥2 was observed in T2D that in the control group (20.2% vs. 11.6%, p=0.004). Participants with T2D and mMRC ≥2 showed a higher HbA1c (8.2 ± 1.6% vs. 7.8 ± 1.6%, p=0.048), longer T2D evolution and higher prevalence of nephropathy. In the multivariate analysis, the presence of T2D [OR=1.95 (1.19 to 3.22), p=0.008] in all the population, and HbA1c [OR=1.19 (1.01 to 1.41), p=0.034] and the presence of diabetic nephropathy [OR=2.00 (1.14 to 3.52), p=0.015] in patients with T2D, predicted a mMRC ≥2. Finally, no differences were observed regarding the SGRQ score among groups. Conclusions: Patients with T2D showed a greater sensation of dyspnea than subjects with normal carbohydrate metabolism. Risk factors included poor metabolic control and the presence of renal disease.

PKN1 Kinase: A Key Player in Adipocyte Differentiation and Glucose Metabolism.

Adipocyte dysfunction is the driver of obesity and correlates with insulin resistance and the onset of type 2 diabetes. Protein kinase N1 (PKN1) is a serine/threonine kinase that has been shown to contribute to Glut4 translocation to the membrane and glucose transport. Here, we evaluated the role of PKN1 in glucose metabolism under insulin-resistant conditions in primary visceral adipose tissue (VAT) from 31 patients with obesity and in murine 3T3-L1 adipocytes. In addition, in vitro studies in human VAT samples and mouse adipocytes were conducted to investigate the role of PKN1 in the adipogenic maturation process and glucose homeostasis control. We show that insulin-resistant adipocytes present a decrease in PKN1 activation levels compared to nondiabetic control counterparts. We further show that PKN1 controls the adipogenesis process and glucose metabolism. PKN1-silenced adipocytes present a decrease in both differentiation process and glucose uptake, with a concomitant decrease in the expression levels of adipogenic markers, such as PPARγ, FABP4, adiponectin and CEBPα. Altogether, these results point to PKN1 as a regulator of key signaling pathways involved in adipocyte differentiation and as an emerging player of adipocyte insulin responsiveness. These findings may provide new therapeutic approaches for the management of insulin resistance in type 2 diabetes.