Free fatty acids as mediators of adaptive compensatory responses to insulin resistance in dexamethasone-treated rats.
BACKGROUND
Chronic low-dose dexamethasone (DEX) treatment in rats is associated to insulin resistance with compensatory hyperinsulinaemia and reduction in food intake. We tested the hypothesis that the elevation in circulating free fatty acids (FFAs) induced by DEX is the common mediator of both insulin resistance and insulin hyperproduction.


METHODS
For this purpose, an anti-lipolytic agent was administered during DEX treatment to lower lipacidaemia for several hours prior to glucose and insulin tolerance tests. Leptin expression in adipose tissue (by Northern blot) and plasma leptin levels (by radioimmunoassay) were also investigated to verify whether a rise in circulating leptin could be responsible for the anorectic effect of DEX.


RESULTS
Our data show that a transient pharmacological reduction of elevated plasma FFA levels abates the post-loading hyperinsulinaemia and counteracts the insulin resistance induced by DEX, supporting the hypothesis that the chronic elevation in FFAs is the common mediator of DEX-induced changes. Despite enhanced leptin expression in white adipose tissue, DEX-treated rats show no significant increase in plasma leptin levels. This suggests that the anorectic effect of DEX should be mediated, at least partially, by other factors, possibly related to the influence of concomitantly elevated plasma FFA and insulin levels on the hypothalamic centers regulating feeding.


CONCLUSIONS
Our results sustain the idea that a prolonged increase in plasma FFA levels plays an important role in the adaptive regulation of glucose and energy homeostasis, not only by potentiating insulin secretion but also by providing a signal of 'nutrient abundance' capable of restraining food intake.
Novelli
Michela
M
Department of Experimental Pathology, University of Pisa, and Ospedale di Cisanello, Italy.
Pocai
Alessandro
A
Chiellini
Chiara
C
Maffei
Margherita
M
Masiello
Pellegrino
P
D000222:Adaptation, Physiological / Q000502:physiology*; D052436:Adipose Tissue, White / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D004435:Eating / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects; D005230:Fatty Acids, Nonesterified / Q000097:blood / Q000502:physiology*; D006706:Homeostasis / Q000187:drug effects; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D000078790:Insulin Secretion; D020738:Leptin / Q000097:blood*; D008297:Male; D009132:Muscles / Q000378:metabolism; D009525:Niacin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014280:Triglycerides / Q000378:metabolism
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D020738:Leptin; D014280:Triglycerides; D009525:Niacin; D003907:Dexamethasone