👤 Donatella Gilio

Partial lipodystrophy (PL) is a rare disease characterized by selective loss of subcutaneous fat. To evaluate changes in apolipoproteins, hepatokines, hormones, appetite regulators, and inflammatory markers in patients with PL treated with leptin, assess postprandial metabolism and 24-hour dynamics, and identify predictors of hepatic and metabolic response to therapy. We studied 19 subjects from our previous clinical study (NCT01679197), which investigated the effect of leptin on metabolic dysfunction-associated steatohepatitis associated with PL. A mixed-meal test was performed in a subgroup of 14 patients, and paired 24-hour frequent sampling with standardized meals was completed in 5 individuals. Leptin treatment led to reductions in apolipoproteins B, CII, CIII, and E ( Leptin therapy modulates lipid metabolism, postprandial glucose regulation, and appetite signaling in patients with PL, with responses associated with metabolic parameters and carbohydrate intake. Show less

Neurodegenerative and inflammatory processes influence the clinical course of multiple sclerosis (MS). The β-site amyloid precursor protein cleaving enzyme 1 (BACE1) has been associated with cognitive dysfunction, amyloid deposition and neuroinflammation in Alzheimer's disease. We explored in a group of 50 patients with relapsing-remitting MS the association between the cerebrospinal fluid (CSF) levels of BACE1, clinical characteristics at the time of diagnosis and prospective disability after three-years follow-up. In addition, we assessed the correlations between the CSF levels of BACE 1, amyloid β (Aβ) 1-40 and 1-42, phosphorylated tau (pTau), lactate, and a set of inflammatory and anti-inflammatory molecules. BACE1 CSF levels were correlated positively with depression as measured with Beck Depression Inventory-Second Edition scale, and negatively with visuospatial memory performance evaluated by the Brief Visuospatial Memory Test-Revised. In addition, BACE CSF levels were positively correlated with Bayesian Risk Estimate for MS at onset, and with Expanded Disability Status Scale score assessed three years after diagnosis. Furthermore, a positive correlation was found between BACE1, amyloid β 42/40 ratio (Spearman's r = 0.334, p = 0.018, n = 50), pTau (Spearman's r = 0.304, p = 0.032, n = 50) and lactate concentrations (Spearman's r = 0.361, p = 0.01, n = 50). Finally, an association emerged between BACE1 CSF levels and a group of pro and anti-inflammatory molecules, including interleukin (IL)-4, IL-17, IL-13, IL-9 and interferon-γ. BACE1 may have a role in different key mechanisms such as neurodegeneration, oxidative stress and inflammation, influencing mood, cognitive disorders and disability progression in MS. Show less