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The monounsaturated fatty acid oleate is the major physiological toxic free fatty
acid for human beta cells
#MMPMID29269872
Plötz T
; Krümmel B
; Laporte A
; Pingitore A
; Persaud SJ
; Jörns A
; Elsner M
; Mehmeti I
; Lenzen S
Nutr Diabetes
2017[Dec]; 7
(12
): 305
PMID29269872
show ga
Free fatty acids (FFAs) can cause glucose intolerance and diabetes. Lipotoxicity
to the pancreatic beta cells is considered to be a major underlying cause for
this phenomenon. The aim of this study was to analyse the toxicity profile of
FFAs in the human EndoC-?H1 beta-cell line and to compare the results with
isolated rat and human islets with special reference to the physiologically most
prevalent FFAs palmitic acid (PA) and oleic acid (OA). Toxicity after a 2-day
incubation with the different FFAs was analysed by the caspase-3 assay and
confirmed by the propidium iodide and annexin V staining tests. The long-chain
saturated PA (C16:0) and the monounsaturated OA (C18:1) were both toxic to human
EndoC-?H1 beta cells and pseudoislets, as well as to rat islets, and, as
confirmed in a pilot experiment, also to human islets. Furthermore, OA provided
no protection against the toxicity of PA. Likewise, elaidic acid (EA, the trans
isomer of OA; trans-OA) was significantly toxic, in contrast to the
non-metabolisable analogues methylated PA (MePA) and methylated OA (MeOA). Fatty
acids with a chain length??< C16 were not toxic in EndoC-?H1 beta cells.
Caspase-3 was also activated by linoleic acid (LA)(C18:2) but not by ?-linolenic
acid (?-LNA)(C18:3). Overall, only long-chain FFAs with chain lengths? >?C14,
which generate hydrogen peroxide in the peroxisomal beta-oxidation, were toxic.
This conclusion is also supported by the toxicity of the branched-chain FFA
pristanic acid, which is exclusively metabolised in the peroxisomal
beta-oxidation. The lack of a protective effect of the monounsaturated fatty acid
OA has important consequences for a beta-cell protective lipid composition of a
diet. A cardioprotective diet with a high OA content does not fulfil this
requirement.
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