Abstract:
Aims: The effects of human serum albumin (HSA) complexed with various free fatty acids (FFAs) on ß-cells
have not been studied in detail. In this study, we examined the effects of HSA and its mutants on FFA-induced
cell viability changes and insulin secretion from the hamster pancreatic insulinoma cell line, HIT-TI5.
Main methods: Cells were exposed to different FFAs in the presence of HSA or its mutants and/or bovine serum
albumin (BSA) for 24 h. Cell viability, apoptosis, insulin secretion, and unbound FFA (FFA u) levels were
determined.
Key findings: In the presence of 0.1 mM HSA, palmitate and stearate induced significant cell death at 0.1 mM or
higher, whereas myristate, palmitoleate, oleate, elaidate, linoleate, linoelaidate, and conjugated linoleate
showed minimal changes on cell viability. Furthermore, oleate and linoleate were clearly cytoprotective
against palmitate-induced cell death. The apoptosis inhibitors, cyclosporin A (csA) and the caspase inhibitor
ZVAD-FMK, did not completely prevent FFA-induced cell death, although ZVAD-FMK blocked apoptosis with
no differences in the presence of either HSA or BSA. In addition, insulin secretion from the cells was
significantly reduced in the presence of HSA/oleate complexes. We also found differential effects of HSA
mutants complexed with FFAs on cell viability.
Significance: In summary, our results showed that saturated FFAs induced more cell death than unsaturated
FFAs. Furthermore, modified HSA/FFA interactions caused by mutations of key amino acids involved in the
binding of FFA to HSA resulted in changes in cell viability, suggesting a possible role of HSA polymorphism on
FFA-induced changes in cellular functions.
