Cardiometabolic characterization in metabolic dysfunction-associated fatty liver disease

BackgroundTo better understand the patient's heterogeneity in fatty liver disease (FLD), metabolic dysfunction-associated fatty liver disease (MAFLD) was proposed by international experts as a new nomenclature for nonalcoholic fatty liver disease (NAFLD). We aimed to evaluate the cardiovascular risk, assessed through coronary artery calcium (CAC) and epicardial adipose tissue (EAT), of patients without FLD and patients with FLD and its different subtypes. MethodsCross sectional study of 370 patients. Patients with FLD were divided into 4 groups: FLD without metabolic dysfunction (non-MD FLD), MAFLD and the presence of overweight/obesity (MAFLD-OW), MAFLD and the presence of two metabolic abnormalities (MAFLD-MD) and MAFLD and the presence of T2D (MAFLD-T2D). MAFLD-OW included two subgroups: metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUHO). The patients without FLD were divided into 2 groups: patients without FLD and without MD (non-FLD nor MD; reference group) and patients without FLD but with MD (non-FLD with MD). EAT and CAC (measured through the Agatston Score) were determined by computed tomography. ResultsCompared with the reference group (non-FLD nor MD), regarding EAT, patients with MAFLD-T2D and MAFLD-MUHO had the highest risk for CVD (OR 15.87, 95% CI 4.26-59.12 and OR 17.60, 95% CI 6.71-46.20, respectively), patients with MAFLD-MHO were also at risk for CVD (OR 3.62, 95% CI 1.83-7.16), and patients with non-MD FLD did not have a significantly increased risk (OR 1.77; 95% CI 0.67-4.73). Regarding CAC, patients with MAFLD-T2D had an increased risk for CVD (OR 6.56, 95% CI 2.18-19.76). Patients with MAFLD-MUHO, MAFLD-MHO and non-MD FLD did not have a significantly increased risk compared with the reference group (OR 2.54, 95% CI 0.90-7.13; OR 1.84, 95% CI 0.67-5.00 and OR 2.11, 95% CI 0.46-9.74, respectively). ConclusionMAFLD-T2D and MAFLD-OW phenotypes had a significant risk for CVD. MAFLD new criteria reinforced the importance of identifying metabolic phenotypes in populations as it may help to identify patients with higher CVD risk and offer a personalized therapeutic management in a primary prevention setting

Rab18 Dynamics in Adipocytes in Relation to Lipogenesis, Lipolysis and Obesity

Lipid droplets (LDs) are organelles that coordinate lipid storage and mobilization, both processes being especially important in cells specialized in managing fat, the adipocytes. Proteomic analyses of LDs have consistently identified the small GTPase Rab18 as a component of the LD coat. However, the specific contribution of Rab18 to adipocyte function remains to be elucidated. Herein, we have analyzed Rab18 expression, intracellular localization and function in relation to the metabolic status of adipocytes. We show that Rab18 production increases during adipogenic differentiation of 3T3-L1 cells. In addition, our data show that insulin induces, via phosphatidylinositol 3-kinase (PI3K), the recruitment of Rab18 to the surface of LDs. Furthermore, Rab18 overexpression increased basal lipogenesis and Rab18 silencing impaired the lipogenic response to insulin, thereby suggesting that this GTPase promotes fat accumulation in adipocytes. On the other hand, studies of the β-adrenergic receptor agonist isoproterenol confirmed and extended previous evidence for the participation of Rab18 in lipolysis. Together, our data support the view that Rab18 is a common mediator of lipolysis and lipogenesis and suggests that the endoplasmic reticulum (ER) is the link that enables Rab18 action on these two processes. Finally, we describe, for the first time, the presence of Rab18 in human adipose tissue, wherein the expression of this GTPase exhibits sex- and depot-specific differences and is correlated to obesity. Taken together, these findings indicate that Rab18 is involved in insulin-mediated lipogenesis, as well as in β-adrenergic-induced lipolysis, likely facilitating interaction of LDs with ER membranes and the exchange of lipids between these compartments. A role for Rab18 in the regulation of adipocyte biology under both normal and pathological conditions is proposed

Impact of Routine and Long-Term Follow-Up on Weight Loss after Bariatric Surgery

Background: Weight loss after bariatric surgery varies among patients. Patients who do not complete long-term follow-up are considered to loose less weight than those with regular follow-up visits. Objective: To evaluate the influence of patients' follow-up compliance on long-term excess weight loss (%EWL) and total weight loss (%TWL) after bariatric surgery, comparing results between gastric bypass (GB) and sleeve gastrectomy (SG). Methods: Patients with up to 5 years of follow-up data after bariatric surgery were included in this retrospective analysis. Patients were divided in 2 groups: those in group 1 who had attended every scheduled postoperative appointment and those in group 2 who had been lost to follow-up before 1 year and were later contacted by telephone. %EWL and %TWL were compared to determine the possible relationship between type of surgery and regularity of the follow-up. Results: A total of 385 patients were included. A significant difference in EWL was observed at 5 years in the SG group (78% for group 1 versus 39% for group 2; p = 0.02) and GB group (75% for group 1 versus 62% for group 2; p = 0.01). No significant differences between surgeries were found when comparing long-term EWL in group 1 patients 77% for SG versus 75% for GB. For group 2 patients, GB achieved greater EWL than SG; p = 0.005. %TWL patients in group 2 showed significant differences in all periods of study (p < 0.05). Conclusion: Bariatric surgery patients who attended all scheduled follow-up appointments experienced significantly greater long-term EWL and TWL than those who did not. GB has apparent increased benefits for weight loss in long-term follow-up when compared with SG for patients who did not attend long-term follow-up. Therefore, continued long-term follow-up of bariatric patients should be encouraged to increase postoperative weight loss results