Background: Understanding the mechanisms of long chain fatty acid (LCFA) uptake in hepatic cells is of high medical importance to treat and to prevent fatty liver disease (FLD). ACSs (Acyl-CoA synthetases) are a family of enzymes that catalyze the esterification of fatty acids (FA) with CoA. Recent studies suggest that ACS enzymes drive the uptake of LCFA indirectly by their enzymatic activity and could promote special metabolic pathways dependent on their localization.The only protein located at the plasma membrane which has consistently been shown to enhance FA uptake is CD36.Aims: The current study investigated whether ACSs and CD36 could regulate hepatic LCFA uptake.Methods and Results: FATP2 and FATP4 were both localized to the ER of HuH7 and HepG2 cells as shown by double immunofluorescence in comparison to marker proteins. ACSL1 was located at mitochondria in both cell lines. Overexpression of FATP2, FATP4 and ACSL1 highly increased ACS activity as well as the uptake of [3H]-oleic acid and fluorescent Bodipy-C12 (B12) fatty acid. Quantitative FACS analysis showed a correlation between ACS expression levels and B12 uptake. FATP2 had the highest effect on B12 uptake of all proteins tested. CD36 was mainly localized at the plasma membrane. Whereas [3H]-oleic acid uptake was increased after overexpression, CD36 had no effect on B12 uptake.Conclusion: Uptake of LCFA into hepatoma cells can be regulated by the expression levels of intracellular enzymes. We propose that ACS enzymes drive FA uptake indirectly by esterification. Therefore these molecules are potential targets for treatment of nonalcoholic fatty liver disease (NAFLD) or steatohepatitis (NASH).

Purpose To describe imaging findings, detection rates and tumor characteristics of breast cancers in a large series of patients with BRCA1 and BRCA2 mutations to potentially streamline screening strategies. Methods An IRB-approved, HIPAA-compliant retrospective analysis of 496 BRCA mutation carriers diagnosed with breast carcinoma from 1999-2013 was performed. Institutional database and electronic medical records were reviewed for mammography and MRI imaging. Patient and tumor characteristics including age at diagnosis, tumor histology, grade, receptor and nodal status were recorded. Results Tumors in BRCA1 mutation carriers exhibited significantly higher nuclear and histological grade compared to BRCA2 (p<0.001). Triple-negative tumors were more frequent in BRCA1 mutation carriers, whereas hormone receptor positive tumors were more frequent in BRCA2 mutation carriers (p<0.001). BRCA2 mutation carriers more frequently presented with ductal carcinoma in situ (DCIS) alone 14% (35/246) and cancers more frequently exhibiting calcifications (p<0.001). Mammography detected fewer cancers in BRCA1 mutation carriers compared to BRCA2 (p=0.04): 81% (186/231) BRCA1 vs. 89% (212/237) BRCA2. MRI detected 99% cancers in each group. Mammography detected cancer in two patients with false negative MRI (1 invasive cancer, 1 DCIS). Detection rates on both mammography and MRI did not significantly differ for women over 40 years and women below 40 years. Conclusions Breast cancers in BRCA1 mutation carriers are associated with more aggressive tumor characteristics compared to BRCA2 and are less well seen on mammography. Mammography rarely identified cancers not visible on MRI. Thus, the omission of mammography in BRCA1 mutation carriers screened with MRI can be considered.

Excess weight loss is highly influenced by the initial BMI. Total weight loss seems to be a better measurement tool abolishing initial weight differences. SG and RYGB do not differ in terms of body composition and weight loss 1 year after surgery.