PNPLA3 Genotype, Arachidonic Acid Intake, and Unsaturated Fat Intake Influences Liver Fibrosis in Hispanic Youth with Obesity.

Non-alcoholic fatty liver disease impacts 15.2% of Hispanic adolescents and can progress to a build-up of scared tissue called liver fibrosis. If diagnosed early, liver fibrosis may be reversible, so it is necessary to understand risk factors. The aims of this study in 59 Hispanic adolescents with obesity were to: (1) identify potential biological predictors of liver fibrosis and dietary components that influence liver fibrosis, and (2) determine if the association between dietary components and liver fibrosis differs by PNPLA3 genotype, which is highly prevalent in Hispanic adolescents and associated with elevated liver fat. We examined liver fat and fibrosis, genotyped for PNPLA3 gene, and assessed diet via 24-h diet recalls. The prevalence of increased fibrosis was 20.9% greater in males, whereas participants with the GG genotype showed 23.7% greater prevalence. Arachidonic acid was associated with liver fibrosis after accounting for sex, genotype, and liver fat (ß = 0.072, p = 0.033). Intakes of several dietary types of unsaturated fat have different associations with liver fibrosis by PNPLA3 genotype after accounting for sex, caloric intake, and liver fat. These included monounsaturated fat (ßCC/CG = -0.0007, ßGG = 0.03, p-value = 0.004), polyunsaturated fat (ßCC/CG = -0.01, ßGG = 0.02, p-value = 0.01), and omega-6 (ßCC/CG = -0.0102, ßGG = 0.028, p-value = 0.01). Results from this study suggest that reduction of arachidonic acid and polyunsaturated fatty acid intake might be important for the prevention of non-alcoholic fatty liver disease progression, especially among those with PNPLA3 risk alleles.

Liver Fat Reduction After Gastric Banding and Associations with Changes in Insulin Sensitivity and ß-Cell Function.

OBJECTIVE: The aim of this study was to examine the relationship between changes in liver fat and changes in insulin sensitivity and ß-cell function 2 years after gastric banding surgery. METHODS: Data included 23 adults with the surgery who had prediabetes or type 2 diabetes for less than 1 year and BMI 30 to 40 kg/m2 at baseline. Body adiposity measures including liver fat content (LFC), insulin sensitivity (M/I), and ß-cell responses (acute, steady-state, and arginine-stimulated maximum C-peptide) were assessed at baseline and 2 years after surgery. Regression models were used to assess associations adjusted for age and sex. RESULTS: Two years after surgery, all measures of body adiposity, LFC, fasting and 2-hour glucose, and hemoglobin A1c significantly decreased; M/I significantly increased; and ß-cell responses adjusted for M/I did not change significantly. Among adiposity measures, reduction in LFC had the strongest association with M/I increase (r = -0.61, P = 0.003). Among ß-cell measures, change in LFC was associated with change in acute C-peptide response to arginine at maximal glycemic potentiation adjusted for M/I (r = 0.66, P = 0.007). Significant reductions in glycemic measures and increase in M/I were observed in individuals with LFC loss >2.5%. CONCLUSIONS: Reduction in LFC after gastric banding surgery appears to be an important factor associated with long-term improvements in insulin sensitivity and glycemic profiles in adults with obesity and prediabetes or early type 2 diabetes.

Galantamine nanoparticles outperform oral galantamine in an Alzheimer's rat model: pharmacokinetics and pharmacodynamics.

Aim: Galantamine is an acetylcholinesterase inhibitor frequently used in Alzheimer's disease management. Its cholinergic adverse effects and rapid elimination limit its therapeutic outcomes. We investigated the pharmacodynamics and pharmacokinetics of 2-week intranasal galantamine-bound chitosan nanoparticles (G-NP) treatment in scopolamine-induced Alzheimer's disease rat model. Materials & methods: Behavioral, neurobiochemical and histopathological changes were assessed and compared with oral and nasal solutions. Brain uptake and pharmacokinetics were determined using a novel validated LC/MS assay. Results: G-NP enhanced spatial memory, exploring behavior and cholinergic transmission in rats. Beta-amyloid deposition and Notch signaling were suppressed and the histopathological degeneration was restored. G-NP potentiated galantamine brain delivery and delayed its elimination. Conclusion: G-NP hold promising therapeutic potentials and brain targeting, outperforming conventional galantamine therapy.