ORIGINAL ARTICLE
Linoleic Acid Decreases Leptin and Adiponectin Secretion
from Primary Rat Adipocytes in the Presence of Insulin
P. Pe
´
rez-Matute Æ J. A. Martı
´
nez Æ A. Marti Æ
M. J. Moreno-Aliaga
Received: 12 September 2006 / Accepted: 18 June 2007 / Published online: 24 July 2007
Ó
AOCS 2007
Abstract Obesity rates have dramatically increased over
the last few decades and, at the same time, major changes
in the type of fatty acid intake have occurred. Linoleic acid,
an n-6 polyunsaturated fatty acid, is an essential fatty acid
occurring in high amounts in several western diets. A
potential role of this fatty acid on obesity has been sug-
gested. Controversial effects of linoleic acid on insulin
sensitivity have also been reported. Thus, the aim of this
study was to examine the direct effects of linoleic acid on
leptin and adiponectin production, two adipokines known
to influence weight gain and insulin sensitivity. Because
insulin-stimulated glucose metabolism is an important
regulator of leptin production, the effects of linoleic acid
on adipocyte metabolism were also examined. For this
purpose, isolated rat adipocytes were incubated with lino-
leic acid (1–200 lM) in the absence or presence of insulin.
Linoleic acid (1–200 lM) significantly decreased insulin-
stimulated leptin secretion and expression (P < 0.05),
however, no changes in basal leptin production were
observed. Linoleic acid also induced a significant decrease
(~20%) in adiponectin secretion (P < 0.05), but only in the
presence of insulin and at the highest concentration tested
(200 lM). This fatty acid did not modify either glucose
uptake or lactate production and the percentage of glucose
metabolized to lactate was not changed either. Together,
these results suggest that linoleic acid seems to interfere
with other insulin signalling pathway different from those
controlling glucose uptake and metabolism, but involved in
the regulation of leptin and adiponectin production.
Keywords Linoleic acid Á Insulin Á Glucose metabolism Á
Adipocytes Á Leptin Á Adiponectin Á Obesity Á
Insulin resistance
Abbreviations
n-6 PUFA n-6 Polyunsaturated fatty acids
Introduction
While the debate continues on whether dietary fat is the
primary determinant of excessive body fat, the evidence is
compelling for the greater importance of types of fat, rather
than the total amount of fat, as a risk for chronic disease
[1]. Thus, several studies have suggested that the type of fat
ingested may be an important determinant in the devel-
opment of obesity and other associated diseases such as
insulin resistance, type 2 diabetes and cardiovascular dis-
eases [2, 3]. In this sense, it has been demonstrated that
saturated fat intake induces obesity and insulin resistance
[4, 5] meanwhile diets rich in fish oils (n-3 PUFAs) seem to
prevent the development of these diseases [6, 7]. Further-
more, body fat accumulation is greater in rats fed a beef
tallow diet (rich in saturated fatty acids) than in rats fed on
diets enriched with other types of fatty acids such as n-3
fatty acids [8] or n-6 PUFAs [9–11].
Concerning the intake of n-6 and n-3 polyunsaturated
fatty acids (PUFAs), a striking rise in the linoleic acid/a
linolenic acid ratio has been observed during the last dec-
ades, which is likely related to an increase in linoleic acid
P. Pe
´
rez-Matute Á J. A. Martı
´
nez Á A. Marti Á
M. J. Moreno-Aliaga (&)
Department of Physiology and Nutrition,
University of Navarra, 31008 Pamplona,
Navarra, Spain
e-mail: mjmoreno@unav.es
123
Lipids (2007) 42:913–920
DOI 10.1007/s11745-007-3092-y