Preliminary report: inhibition of cellular proteasome activity by free fatty acids

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

There is evidence in animal studies that free fatty acids (FFA) can decrease protein degradation, but the exact mechanism is not known. We have shown that FFA can inhibit proteasome activity in vitro by interacting with insulin-degrading enzyme. Here we show that FFA can also inhibit the proteasome in whole cells. HepG2 cells were treated with various FFA, and proteasome activity was measured using a cell-permeable substrate for the chymotrypsin-like activity. Octanoic acid, a medium-chain fatty acid, did not affect proteasome activity. However, oleic and linoleic acids inhibited the chymotrypsin-like activity up to 80%, with approximate IC50s of 80 and 40 μmol/L, respectively. Insulin also inhibited but was not additive with the FFA, suggesting that they work through the same mechanism. These results show that the proteasome can be inhibited by FFA in whole cells and suggest that insulin-degrading enzyme may mediate this effect. This mechanism may be applicable to whole animals and represents a means to integrate hormonal and nutrient signals on the control of protein degradation.

Original languageEnglish (US)
Pages (from-to)1047-1049
Number of pages3
JournalMetabolism: Clinical and Experimental
Volume58
Issue number8
DOIs
StatePublished - Aug 1 2009

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Proteasome Endopeptidase Complex
Nonesterified Fatty Acids
Insulysin
Chymotrypsin
Proteolysis
Oleic Acids
Linoleic Acids
Hep G2 Cells
Fatty Acids
Insulin
Food

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Preliminary report : inhibition of cellular proteasome activity by free fatty acids. / Hamel, Frederick G.

In: Metabolism: Clinical and Experimental, Vol. 58, No. 8, 01.08.2009, p. 1047-1049.

Research output: Contribution to journalArticle

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