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Dietary Fat Influences Testosterone, Cholesterol, Aminopeptidase A, and Blood Pressure in Male Rats

Short Communication 1
Segarra AB et al. Dietary Fat and Blood Pressure Control Horm Metab Res 2008 ; 40: 1 – 3
HMR/473/12.2.2008/Macmillan
received
accepted
Bibliography
DOI 10.1055/s-2008-1046800
Horm Metab Res 2008 ;
40: 1 – 3
© Georg Thieme Verlag KG
Stuttgart · New York
ISSN 0018-5043
Correspondence
M. Ramirez
Unit of Physiology
University of Ja é n
Bldg B-3-263
23071 Ja é n
Spain
Tel.:
Fax: + 34 / 953 / 21 29 43
msanchez@ujaen.es
Dietary Fat Infl uences Testosterone, Cholesterol,
Aminopeptidase A, and Blood Pressure in Male Rats
Authors A . B . S e g a r r a
1
, M . R a m i r e z
1
, I . B a n e g a s
1
, F. A l b a
2
, F. V i v e s
3
, M . d e G a s p a r o
4
, E . O r t e g a
2
, E . R u i z
3
, I. Prieto
1
Affi liations
1
Unit of Physiology, University of Ja é n, Ja é n, Spain
2
Department of Biochemistry and Molecular Biology, University of Granada, Granada, Spain
3
Department of Physiology, University of Granada, Granada, Spain
4
MG Consulting Co., Rossemaison, Switzerland
Introduction
&
A high intake of monounsaturated fat (MUFA)
has been proposed to be a dietary factor able to
decrease the incidence of cardiovascular disease
and hypertension [1] . It has been shown that an
increase in the saturation of dietary fat results in
increased concentrations of total plasma choles-
terol [2] and higher blood pressure [3] . It was
previously shown that serum total cholesterol
levels were higher in mice fed diets containing
saturated oils than in those consuming unsatu-
rated fat. In addition, angiotensin II – degrading
(aminopeptidase A) activity increased progres-
sively with the degree of saturation of dietary
fatty acids [4] . A subsequent study found that
dietary fatty acid composition affected amino-
peptidase A activity in the testes of mice, sug-
gesting a role for fatty acids in male reproductive
functions, including androgen synthesis [5] . It
was recently observed that a diet enriched with
Iberian pig lard remarkably increased serum tes-
tosterone levels in comparison to diets contain-
ing other types of fatty acids with different
degrees of saturation [6] . This and other studies
suggested an infl uence of gonadal steroids and
cholesterol on angiotensin-degrading activities
[7] . Other actions of gonadal steroids by non-
genomic-dependent mechanisms have been
reported, such as stimulation of insulin secretion
and Ca
2 +
uptake as well as vasodilatory effects
[8, 9] . In the present report we analyze the effect
of various diets enriched in fatty acids with dif-
ferent degrees of saturation on systolic blood
pressure, plasma levels of testosterone, total cho-
lesterol, HDL cholesterol, LDL cholesterol, and
angiotensin II – degrading activity.
Materials and Methods
&
Six groups of adult male Wistar rats (200 250 g,
n = 8 in each group) were fed with isocaloric diets
for 16 weeks. Each diet was supplemented with
10 % of the oil under investigation: sesame oil,
sunfl ower oil, fi sh oil, olive oil, Iberian pig lard, or
coconut oil. The characteristics of the different
types of dietary fat compared in this study are
summarized in Table 1 [10, 11] .
At the end of the feeding period, systolic blood
pressure in each rat was recorded, and then the
animals were killed by Equithesin anesthesia.
Blood samples were obtained and plasma was
isolated by centrifugation for 10 minutes at
2000 g and stored at 20 ° C. Plasma testosterone
levels were measured by radioimmunoassay as
previously reported [6] and expressed as nano-
grams per milliliter. Cholesterol levels were
determined colorimetrically with a commercial
kit purchased from Sigma. Aminopeptidase A
activity was determined with a fl uorometric
assay using glutamyl- -naphthylamide as the
substrate, as previously described [12] . Systolic
blood pressure was measured with a tail-cuff
plethysmograph (LE 5001 Pressure Meter, Letica
SA, Barcelona, Spain) in trained, unanesthetized
animals as previously reported [13] . For the sta-
tistical analysis we used one-way analysis of
variance to analyze differences between groups.
Post-hoc comparisons were made with Tukey s
test. P-values below 0.05 were considered signi-
cant.
Results and Discussion
&
The results are summarized in
F i g . 1 . R a t s f e d
with the fi sh oil or Iberian pig lard diet had sig-
nifi cantly lower blood pressure, plasma total
cholesterol, and LDL cholesterol (p < 0.001) than
animals fed with the other diets. Plasma HDL
Short Communication2
Segarra AB et al. Dietary Fat and Blood Pressure Control Horm Metab Res 2008 ; 40: 1 – 3
HMR/473/12.2.2008/Macmillan
cholesterol was higher in rats fed the olive oil, Iberian pig lard,
and coconut oil diets but was signifi cantly lower (p < 0.01) in ani-
mals given the sesame oil diet. The sunfl ower and fi sh oil diets
showed a tendency toward lower HDL cholesterol, but the dif-
ferences did not reach statistical signifi cance. Testosterone lev-
els were signifi cantly higher (ranging from two-fold to four-fold)
in animals fed the Iberian pig lard enriched diet than in rats fed
olive oil (p < 0.001), sh oil (p < 0.01), or sesame, sunfl ower, or
Table 1 Fatty acid composition of food fats (grams fatty acid per 100 g total fatty acids)
Fatty acid type Sesame oil [11] Sunfl ower oil [11] Fish oil [11] Olive oil [11] Iberian pig lard [10] Coconut oil [11]
C
8:0
caprylic 10.1
C
10:0
capric 6.6
C
12:0
lauric 45.8
C
14:0
myristic 0.1 4.5 1.2 18.4
C
16:0
palmic 8.9 6.6 0.6 11.8 20.0 8.0
C
16:1
palmitoleic 0.3 0.1 22.1 0.9 2.9
C
16:2
hexadecadienoic 2.8
C
17:0
margaric 0.8
C
18:0
stearic 6.0 4.3 6.1 2.8 6.3 2.4
C
18:1
oleic 40.7 22.4 21.7 74.5 59.1 6.0
C
18:2
linoleic 41.7 65.2 2.1 8.7 9.4 1.7
C
18:3
linolenic 1.7 0.3 1.2 1.0
C
18:4
stearidonic 0.5
C
20:0
arachidic 0.8 0.4
C
20:1
eicosenoic 2.0
C
20:4
arachidonic 3.0
C
20:5
timnodonic 13.2
C
22:0
behenic 0.7
C
22:5
docosapentaenoic 1.5
C
22:6
clupanodonic 17.3
SAFA 15.7 12 12 13.2 27.6 86.5
MUFA 41 22.4 45.8 73.2 62 5.8
PUFA 43.4 60.7 41.6 8.9 9.4 1.8
SAFA / MUFA 0.38 0.53 0.26 0.18 0.44 14.9
SAFA / PUFA 0.36 0.19 0.28 1.4 2.9 48.0
SAFA = saturated fatty acids; MUFA = monounsaturated fatty acids; PUFA = polyunsaturated fatty acids
0
2
4
6
8
10
12
ng/ml
TESTOSTERONE
*
**
***
0
10
20
30
40
pmol/min/mg prot
AMINOPEPTIDASE A
***
***
0
40
80
120
160
200
mmHg
SYSTOLIC BLOOD PRESSURE
***
***
S
0
40
80
120
160
200
mg/dL
TOTAL CHOLESTEROL
***
***
0
10
20
30
40
50
mg/dL
HDL CHOLESTEROL
**
0
30
60
90
120
150
mg/dL
LDL CHOLESTEROL
***
***
CLOFSF
SCLOFSF
SCLOFSF
SCLOFSF
SCLOFSF
SCLOFSF
Fig. 1 Systolic blood pressure and plasma levels of testosterone, total cholesterol, HDL cholesterol, LDL cholesterol, and aminopeptidase A activity in adult
male Wistar rats fed diets enriched with sesame oil (S), sunfl ower oil (SF), fi sh oil (F), olive oil (O), Iberian pig lard (L), or coconut oil (C). Values are means ±
SEM, n = 8. Total cholesterol was signifi cantly lower in groups F and L than in the other groups. HDL cholesterol was signifi cantly lower in group S than in groups
L and C. LDL cholesterol was signifi cantly lower in group L than in groups S, SF, O, and C and was signifi cantly lower in group F than in group C. Testosterone
concentration was signifi cantly higher in group L than in the other groups. Aminopeptidase A was signifi cantly lower in group S than in groups SF, O, L, and C
and was signifi cantly lower in group F than in group L. Systolic blood pressure was signifi cantly lower in groups L and F than in groups S, SF, O, and C. * p < 0.05,
* * p < 0.01, * * * p < 0.001.
Short Communication 3
Segarra AB et al. Dietary Fat and Blood Pressure Control Horm Metab Res 2008 ; 40: 1 – 3
HMR/473/12.2.2008/Macmillan
coconut oil (p < 0.05). The diet containing sesame oil signifi cantly
decreased (p < 0.001) aminopeptidase A activity compared with
the other types of dietary fat except for fi sh oil, whereas in ani-
mals fed the latter diet, aminopeptidase A activity was lower
(p < 0.001) than in the Iberian pig lard group. Interestingly, only
rats treated for 16 weeks with the Iberian pig lard diet showed a
marked increased in plasma testosterone levels, which paral-
leled a reduction in total and LDL cholesterol and a decrease in
blood pressure.
To our knowledge, the only comparable study published to date
on the infl uence of fatty acid saturation is a previous report by
Arechaga and colleagues [4] . In this study Balb / C mice were
treated with different diets containing 2.4 g fat per 100 g for 10
weeks. The diet containing pig lard signifi cantly increased total
cholesterol compared with mice fed a diet enriched with sun-
ower oil. No difference in aminopeptidase A activity was
observed between the group that consumed pig lard and the
other groups. However, it should be noted that the present study
differed in the experimental model used (rats rather than mice),
the duration of treatment (16 weeks rather than 10 weeks), and
the degree of fat enrichment of the diet (10 g per 100 g food vs.
2.4 g per 100 g). The most important difference is that Iberian pig
lard differs in composition from the pig lard used by Arechaga
and colleagues, which was rich in oleic acid C18:1 (41.1 % ), satu-
rated fatty acids (SAFA; 37.4 % ), monounsaturated fatty acids
(MUFA; 45.9 % ), and polyunsaturated fatty acids (PUFA; 11.3 % )
[4] . In contrast, Iberian pig lard contains a higher percentage of
MUFA + PUFA (62 + 9.5 % ) (mainly oleic C18:1, 59.1 % ) compared
with SAFA (27.6 % ). We therefore propose that the discrepancy
between the two studies is related to the difference in the
unsaturated / saturated fat ratios of the different lard-containing
diets. Indeed, the SAFA / MUFA ratio is 0.44 for Iberian pig lard
and 0.81 for regular pig lard, and the SAFA / PUFA ratio is 2.9 for
Iberian pig lard and 3.4 for regular pig lard. The most remarkable
nding is the greater effect of the Iberian pig lard diet on testo-
sterone and lipid levels compared with the effects of other fat-
enriched diets.
The benefi cial effects of testosterone [14] and the deleterious
infl uence of dyslipidemia [15] on cardiovascular function are
well documented. The high levels of aminopeptidase A activity
in animals that consumed the Iberian pig lard enriched diet
might refl ect the decreased pressor responsiveness to angio-
tensin II caused by increased inactivation of angiotensin II by the
enzyme. Angiotensin II is indeed metabolized to angiotensin III
by aminopeptidase A activity [12] . Moreover, angiotensin II is
considered the main effector peptide of the renin angiotensin
system, and more than a century of research has documented its
widespread involvement in the pathophysiology of cardiovascu-
lar disease [16] .
However, while both sesame oil and fi sh oil decrease amino-
peptidase A activity, only fi sh oil produces a fall in blood pres-
sure. There is therefore an apparent discrepancy with Iberian pig
lard in that it increases aminopeptidase A activity but also
decreases blood pressure. It should be noted, however, that ses-
ame oil does not improve the lipid profi le. Moreover, there is a
signifi cant decrease in HDL cholesterol for the sesame oil group.
In contrast, both fi sh oil and Iberian pig lard have a clear benefi -
cial effect on lipids. This suggests that aminopeptidase A is not
the only or main factor that infl uences blood pressure. There is
no doubt that lipids have a direct effect on vessel walls and
therefore control their stiffness [17] . The benefi cial effect of fi sh
oil on the lipid profi le may therefore compensate for the
decreased aminopeptidase A activity, which is not the case for
the sesame oil. The lipid profi le, together with the level of testo-
sterone, that results from the type of fat used in the diet may
therefore account (in part) for that discrepancy.
Taken together, the present results suggest that the use of Ibe-
rian pig lard (a type of fat with a low SAFA / MUFA ratio and a
moderately low SAFA / PUFA ratio) in the diet may benefi t cardio-
vascular function in adult male rats. The effect of dietary Iberian
pig lard also should be investigated in female rats to gain a fuller
understanding of the present results, which suggest a benefi cial
role for testosterone.
Acknowledgments
&
This research and work done by A. B. Segarra were supported by
a grant from the University of Ja é n, (ref. UJA2003-015). The
authors thank K. Shashok for improving the use of English in the
manuscript.
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... The reduction in SAFA in substitution by MUFA attenuates the increase in blood pressure (BP) [4]. These alterations, depending on the degree of fatty acid saturation, are related to changes in the systemic or local renin-angiotensin systems (RAS) [5][6][7][8][9][10]. The activation of the RAS participates in the development of MetS, heart failure [11], and pathophysiology of hypertension [4,7,[12][13][14][15][16][17][18][19][20][21][22][23][24][25]. ...
... [4,7,9]. Elevated plasma cholesterol levels are another important risk factor widely recognized for its relationship with angiotensin metabolism [4,5,7,10,12,72], with Mediterranean countries showing lower rates of heart disease than other countries due to the usual diet rich in olive oil [75]. ...
... HFDs alter the baroreceptor reflex [76], and the type of fatty acid that makes up the diet is capable of modulating the central [10,26,77] and local RAS regulatory APs [4,5,7,9,57]. Our results show that the VOO diet favored the stabilization of the RAS with respect to the Bch diet, by lowering the values of GluAP (mb) activities in the aorta, ArgAP (mb) in the ventricle and aorta, and CysAP (mb) in the atrium. ...
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High-fat diets (HFD) have been widely associated with an increased risk of metabolic disorders and overweight. However, a high intake of sources that are rich in monounsaturated fatty acids has been suggested as a dietary agent that is able to positively influence energy metabolism and vascular function. The main objective of this study was to analyze the role of dietary fats on hepatic peptidases activities and metabolic disorders. Three diets: standard (S), HFD supplemented with virgin olive oil (VOO), and HFD supplemented with butter plus cholesterol (Bch), were administered over six months to male Wistar rats. Plasma and liver samples were collected for clinical biochemistry and aminopeptidase activities (AP) analysis. The expression of inducible nitric oxide synthase (iNOS) was also determined by Western blot in liver samples. The diet supplement with VOO did not induce obesity, in contrast to the Bch group. Though the VOO diet increased the time that was needed to return to the basal levels of plasma glucose, the fasting insulin/glucose ratio and HOMA2-%B index (a homeostasis model index of insulin secretion and valuation of β-cell usefulness (% β-cell secretion)) were improved. An increase of hepatic membrane-bound dipeptidyl-peptidase 4 (DPP4) activity was found only in VOO rats, even if no differences in fasting plasma glucagon-like peptide 1 (GLP-1) were obtained. Both HFDs induced changes in hepatic pyroglutamyl-AP in the soluble fraction, but only the Bch diet increased the soluble tyrosyl-AP. Angiotensinase activities that are implicated in the metabolism of angiotensin II (AngII) to AngIV increased in the VOO diet, which was in agreement with the higher activity of insulin-regulated-AP (IRAP) in this group. Otherwise, the diet that was enriched with butter increased soluble gamma-glutamyl transferase (GGT) and Leucyl-AP, iNOS expression in the liver, and plasma NO. In summary, VOO increased the hepatic activity of AP that were related to glucose metabolism (DPP4, angiotensinases, and IRAP). However, the Bch diet increased activities that are implicated in the control of food intake (Tyrosine-AP), the index of hepatic damage (Leucine-AP and GGT), and the expression of hepatic iNOS and plasma NO. Taken together, these results support that the source of fat in the diet affects several peptidases activities in the liver, which could be related to alterations in feeding behavior and glucose metabolism.
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Although at present depression is one of the most disabling disorders in our social environment, the understanding of its pathogenesis and the resources for its treatment are still unsatisfactory. The importance of brain asymmetry in the pathogenesis of disorders in brain function, including mood disorders such as depression, is a highly unexplored, sometimes underrated, and even ignored topic. It is important to note that the basal and pathological functional lateralization must have an underlying neurochemical substrate. It is also necessary to indicate that the brain asymmetry extends to a neurovisceral integration whose behavior may also be lateralized. One of the most studied axis from the functional point of view is the brain-heart connection, in whose operation there are observations that suggest an asymmetric behavior in basal conditions that is modified by central and peripheral changes, as well as by pharmacological treatments. There are evidences that connect cardiovascular function, neurochemical asymmetries, and depression. A deep understanding of the bilateral behavior of the brain following pathophysiological changes in blood pressure as well as pharmacologically induced, can provide us with therapeutic suggestions for the treatment of depression. In this article, we analyze remarkable results of some representative selected contributions, with which we discuss our proposal on the relationship between hypertension, depression and neurochemical asymmetry.
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