Activation of Hypothalamic-pituitary-adrenal (HPA) Axis by a Fall in Plasma FFA: Role of Individual FFAs and Existence of a Threshold

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SUN 72-87-HPA Axis
Sunday, June 16, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SUN-79
Jang H Youn*1, Young Taek Oh2 and Jinyub Kim2
1USC Keck School of Medicine, Los Angeles, CA, 2USC Keck School of Medicine
We previously showed that the brain responds to a fall in plasma FFA level by activating the HPA axis, which would increase lipolysis and restore plasma FFA levels (1).  Because plasma contains a variety of FFA species, in the present study, we tested whether the activation of the HPA axis is elicited by a fall in total or specific FFA levels.  To address this issue, nicotinic acid (NA; 30 µmol/h) was intravenously infused in rats to decrease plasma FFA levels.  To prevent decreases in individual FFA levels differentially, the NA infusion was combined with an infusion of oils containing different fat compositions; coconut, olive, and safflower oils were used (n=7 for each), which are mainly composed of saturated, monounsaturated (oleic acid), and polyunsaturated (linoleic acid) fat, respectively.  NA infusion caused 90% decreases in total plasma FFA levels, accompanied by a 2 to 3-fold increase in both plasma ACTH and corticosterone levels (P<0.01).  The oil infusions during NA infusion caused significantly less decreases in total plasma FFA (30, 50, and 55%, with coconut, safflower, and olive oil, respectively), accompanied by significantly reduced ACTH and corticosterone responses.  There was a strong inverse relationship between plasma corticosterone and total FFA levels across experiments (R = 0.59; P<0.001), independent of oils infused, suggesting that these responses were elicited by decreases in total rather than specific FFA levels.  We are currently quantifying individual FFA levels in plasma using a LC-MS method to further substantiate this idea.  In addition, the relationship between plasma corticosterone and total FFA levels suggested that there may be a threshold of 30-40% for a fall in plasma FFA to increase plasma corticosterone.  To test this idea, in a separate experiment, NA was infused at lower rates to decrease plasma FFA only by 30-40%.  Under this condition, plasma corticosterone levels were not increased, demonstrating that there is indeed a threshold for the effect of reduced plasma FFA to activate the HPA axis, similar to the well-known threshold for the effect of hypoglycemia to elicit counterregulatory responses.  In conclusion, our data indicate that activation of the HPA axis occurs in response to a fall in total rather than specific FFA levels, and it requires a fall in total plasma FFA of more than 30-40% (i.e., threshold) from basal levels.

Nothing to Disclose: JHY, YTO, JK

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