Odd-Chain Fatty Acids Predict Insulin Sensitivity in People with T2DM and Protect HepG2 Cells from Palmitate-Induced Insulin Resistance Via PPARα

Ogwu John Ikwuobe, Karan Rana, James Brown, Chathyan Pararasa, Kiran Shabir, Srikanth Bellary, Clifford Bailey, Helen Griffiths

Research output: Contribution to journalConference abstractpeer-review


Lipid-induced dysfunction of the liver, especially steatohepatitis, is becoming increasingly prevalent and may be an important link between obesity and type 2 diabetes (T2DM). Elevated circulating saturated fatty acids contribute to steatohepatitis and T2DM while other plasma free fatty acids appear protective. Activated PPARα is involved in regulating hepatic lipid accumulation by upregulating genes responsible for fatty acid transport and metabolism.

We examined the hypothesis that specific fatty acids predict insulin sensitivity in T2DM patients and modulate risk of steatohepatitis by activating PPARα.

The plasma fatty acid profile of patients with T2DM (n=43) and healthy control subjects (n=45) was analysed using gas chromatography. An in vitro model of terminally differentiated (d)HepG2 cells was used to determine the mechanism of effect of novel protective fatty acids on insulin resistance and hepatocyte dysfunction.

Plasma levels of odd-chain saturated fatty acids (OCSFA) predicted fasting plasma glucose in a multiple regression model, after adjusting for age, BMI and gender. OCSFA protected dHepG2 cells from palmitate-induced insulin resistance and cellular dysfunction; by increasing cellular glycogen content, cellular monounsaturated fatty acid (MUFA) concentration and reducing output of glucose and TNFα. The PPARα antagonist GW6471 blocked the increase of MUFA due to OCSFA in palmitate-exposed hepatocytes. Furthermore, OCSFA increased PPARα activity in palmitate-exposed hepatocytes more than the PPARα agonist fenofibrate. OCSFA induced upregulation of the PPARα targets, stearoyl Co-A desaturase 1 and fatty acid synthase in palmitate-exposed hepatocytes.

In summary, OCSFA inversely associates with insulin resistance and promotes MUFA accumulation via a PPARα-dependent pathway, exerting a protective effect against hepatocyte dysfunction.
Original languageEnglish
Article numberS174
JournalFree Radical Biology and Medicine
Issue numberSuppl.
Publication statusPublished - 1 Nov 2016
EventSFRBM 2016 - San Francisco, United States
Duration: 16 Nov 201619 Nov 2016


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