Regulation of PPAR but not obese
gene expression by dietary fat
supplementation
Michael E. Spurlock,* Karen L. Houseknecht,* Carla P. Portocarrero,*
Steven G. Cornelius,
²
Gawain M. Willis,
²
and Christopher A. Bidwell*
*Purdue University, West Lafayette, IN USA and
²
Purina Mills, Inc., St. Louis, MO USA
Leptin, the product of the obese gene, and peroxisome proliferator activated receptor gamma (PPAR) are
important regulators of energy metabolism, adipogenesis, and immune function. In rodent models, both genes
seem to respond at the mRNA and/or protein levels to dietary fat consumption. To determine the effect(s) of
dietary saturated and polyunsaturated fatty acids on the expression (mRNA abundance) of these genes, adipose
tissue was obtained from pigs fed three different dietary fat sources. Corn-soybean meal diets containing no
added fat (NO, control) or 10% beef tallow (BT), safflower oil (SO), or fish oil (FO) were fed ad libitum (n =
12) for 12 weeks. The abundance of obese, PPAR1, and PPAR2 mRNA was quantified relative to 18S rRNA
using ribonuclease protection assays. The gain:feed ratio was improved (P 0.05) 21% by all fats with a
corresponding reduction (P 0.05) in feed intake. Relative to pigs fed NO, serum total cholesterol was increased
(P 0.01) in pigs fed BT and triglyceride and nonesterified fatty acid concentrations were increased (P 0.01)
by all supplemental fats. Serum insulin was increased (P 0.10) only by SO. Neither obese nor PPAR1 mRNA
abundance were responsive to added fat (P 0.15). However, the abundance of PPAR2 mRNA was increased
fourfold by SO compared with the NO diet. These data indicate that the abundance of obese mRNA is independent
of dietary fat consumption per se, whether saturated or unsaturated, when feed consumption is reduced due to
greater dietary caloric density. Furthermore, we provide evidence that expression of the PPAR2 gene in porcine
adipose tissue is selectively responsive to SO (presumably linoleic acid, 18:2n-6). (J. Nutr. Biochem. 11:
260 –266, 2000) © Elsevier Science Inc. 2000. All rights reserved.
Keywords: porcine; PPAR; leptin; fatty acids; dietary fat
Introduction
The peroxisome proliferator activated receptors (PPARs)
are members of the nuclear hormone receptor superfamily
and have been linked to myriad biological processes includ-
ing glucose homeostasis, monocyte function, lipid metabo-
lism, and adipocyte differentiation.
1–3
To date, there are
three known PPARs: , , and , with PPAR having at
least three isoforms that originate from the use of different
promoters and alternative splice sites.
4,5
It is possible that
there are no functional differences in the PPAR isoforms.
However, PPAR2 has received much attention recently
because it is highly expressed in adipose tissues compared
with other tissues and is associated with adipocyte differ-
entiation and lipid filling. Similarly, leptin, the product of
the obese gene, is a key regulator of energy balance and
metabolism in mammalian species
6,7
and is also an integral
component of specific immunologic processes.
8,9
Although
there is a paucity of information regarding endogenous
ligands for the PPAR proteins, some prostaglandins
10
and
polyunsaturated fatty acids (PUFA), including 18:2n-6,
11
have been implicated as activators. As regards the obese
gene, regulatory factors known to date include glucose,
nonesterified fatty acids (NEFAs), cyclic adenosine mono-
phosphate (cAMP), cortisol, insulin, and growth hormone.
Furthermore, increased dietary fat consumption may in-
crease obese mRNA and/or circulating leptin concentra-
tions, even when adiposity is not changed.
Collectively, several findings indicate a possible bio-
chemical linkage of PPAR and leptin. Recent studies by
Address correspondence to Dr. Michael E. Spurlock, Purdue University,
3-230 Lilly Hall, West Lafayette, IN 47907 USA.
Presented in part at the annual meeting of the American Society of Animal
Sciences, July 20 –24, 1999, Indianapolis, IN USA.
Received November 11, 1999; accepted February 11, 2000.
J. Nutr. Biochem. 11:260 –266, 2000
© Elsevier Science Inc. 2000. All rights reserved. 0955-2863/00/$–see front matter
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