Download Weight loss in obesity reduces epicardial fat thickness

J Appl Physiol 106: 1–2, 2009;
doi:10.1152/japplphysiol.91396.2008.
Invited Editorial
Weight loss in obesity reduces epicardial fat thickness; so what?
Harold S. Sacks
Department of Medicine, University of Tennessee Health Science Center; and The Baptist Heart Institute, Baptist Memorial
Hospital, Memphis, Tennessee
Address for reprint requests and other correspondence: H. S. Sacks, Dept. of
Medicine, Univ. of Tennessee Health Science Center, 6027 Walnut Grove
Road, Memphis, TN 38120 ([email protected]).
http://www. jap.org
(BMI) ⬃ 31 kg/m2] Japanese men was reduced after 3 mo of
an aerobic exercise training program. Daily caloric intake
was kept constant from the start to the end of the study so
that the 3.6-kg body weight loss was explained by increased
energy expenditure. Mean epicardial fat thickness decreased
from 8.11 to 7.39 mm, a 0.72-mm statistically significant
difference. Exercise training decreased blood pressure and
VAT area, measured by CT scan, and increased insulin
sensitivity. The percent reduction in EAT thickness from
baseline was less than the percent decrease in VAT area
from baseline. In another study (6), a greater percent reduction in EAT thickness relative to that in waist circumference
occurred after 6 mo on a very low calorie (900 kcal/day)
diet. This suggests that the method used to attain weight loss
may be responsible for relative differences in fat loss in
EAT and VAT seen in the two studies.
The study of Kim et al. (8) investigated exercise training
with isocaloric intake. This can be compared and contrasted
with the results of two other studies summarized in Table 1 that
also used ECHO to measure RV EAT thickness before and
after weight loss induced by bariatric surgery (12) or by
supervised caloric restriction without exercise (6). The number
of patients in each group was small and heterogeneous. There
was variability in mean pretreatment thickness and in the
decrease in posttreatment thickness, possibly due to ethnicity
rather than to adiposity. Thus morbidly obese South Florida
patients [body wt, 154 kg; BMI, 54 kg/m2] (12) had less initial
EAT thickness than the mildly obese Japanese men [body wt,
88 kg; BMI, 31 kg/m2] (8) but approximately similar reductions of ⬃1 mm after weight loss. In contrast, the morbidly
obese Caucasian Canadian patients [body wt, 154 kg; BMI, 45
kg/m2] (6) had the thickest EAT layer and the largest decrease
of ⬃4 mm. A key observation (6) was the improvement in left
ventricular (LV) mass and diastolic function, which correlated
better with the decrease in EAT than in waist, suggesting that
excess local fat around the heart is pathological. Notably, EAT
mass correlates directly with intramyocardial triglyceride content (7), so the deleterious factor causing LV dysfunction (6, 7)
might be cardiomyocyte triglyceride overload leading to lipotoxic cardiomyopathy (10), rather than adipokine-mediated
cardiomyocellular damage or physical constraints imposed on
the myocardium by too much EAT.
So what does it mean if EAT thickness goes down after
weight loss? If EAT expansion during the evolution of
obesity proves to be proinflammatory and deleterious for
myocardial and/or coronary function, then EAT shrinkage
by weight loss may be therapeutically important. What
future investigations can be devised to test this hypothesis?
Human studies could be difficult to do because they should
include larger numbers of people from different ethnic
groups using circulating inflammatory or other biomarkers
as yet undefined that specifically target EAT pathogenicity,
and a radiological technique that measures EAT volume (see
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of human epicardial adipose tissue
(EAT) are not well defined because this strategically located
white adipose tissue (WAT) depot is difficult to access and
study, and most of the information about it comes from
humans with severe cardiac diseases undergoing open heart
surgery or by implication from animal experiments (9, 10).
Hypothetically, its functions include lipid storage for myocardial energy use, coronary artery mechanical buffering
against arterial wave torsion, coronary artery vasomotion
and remodeling, protection of the cardiac and coronary autonomic nerve supply, and expression and secretion of adipokines,
a collective definition for WAT-derived hormones, growth factors, coagulation mediators, and pro- and anti-inflammatory cytokines (9 –11).
Echocardiography (ECHO), computed tomography (CT),
and magnetic resonance imaging (MRI) have been used to
quantitate EAT thickness or volume in healthy lean and obese
subjects and in patients with coronary atherosclerosis (CAD)
(1–5, 12). One rationale driving these studies is that EAT, itself
visceral fat by definition, shares some common features with
the more comprehensively studied mesenteric/omental visceral
adipose tissue (VAT). Thus 1) each has the same intra-abdominal embryological derivation (10); 2) each depot’s mass increases in obesity (3, 5, 12); 3) the increase in size of one
directly correlates with the other (4); and 4) their increases
show significant independent associations with established
cardiovascular risk predictors, such as high blood pressure, low
blood high-density lipoprotein (HDL)-cholesterol, high triglycerides, and insulin resistance (3, 5, 12). Putatively, EAT might
exhibit a proinflammatory adipokine profile in obesity like
VAT and play a role in coronary atherogenesis (9, 10). Expansion of adipocytes with triglyceride is thought to be the trigger
for increased expression and production of inflammatory cytokines such as TNF-␣, monocyte chemoattractant protein-1
(MCP-1), IL-1␤, ⫺6, and ⫺8, and plasminogen activator
inhibitor-1 (PAI-1), and decreased expression and production
of leptin and vasoprotective adiponectin by the various cell
types that constitute VAT (10).Importantly, there are no published data yet that demonstrate a VAT-like adipokine profile
in EAT from obese humans. This primary metabolically mediated pathophysiological inflammatory response of VAT (and
potentially of EAT) to fat loading must be distinguished from
the secondary proinflammatory adipokine response in EAT
overlying coronary atherosclerotic inflammation (9, 10).
In a study in the Journal of Applied Physiology, Kim et al.
(8) report the novel finding, which is a significant addition to
current knowledge in the field, that EAT thickness measured
by ECHO over the free wall of the right ventricle (RV) of
obese [mean body weight ⬃ 88 kg; body mass index
THE PHYSIOLOGICAL ROLES
Invited Editorial
2
Table 1. Effect of weight loss in obesity on epicardial fat thickness measured by ECHO
Study (Ref. No.)
Sex, n
Ethnicity
Age, yr
Initial body wt, kg
Initial BMI, kg/m2
Intervention
Duration
Weight loss, kg
Epicardial fat thickness
Preintervention, mm
Postintervention, mm
Decrease, mm
Decrease, %
LV mass and function
Willens et al. (12)
Iacobellis et al. (6)
Kim et al. (8)
15F/8M
C7/AA7/H9
44⫾11
154⫾10
54⫾12
Bariatric surgery
6 mo postoperative
40⫾14
12F/8M
C
35⫾10
154⫾17
45⫾5
900 kcal/day
3 mo
25⫾10
24M
Japanese
49⫾10
88⫾11
31⫾3
Exercise 3 days/wk
3 mo
3.6⫾1
5.3⫾2.4
4.0⫾1.6
1.3⫾1.9
24
Not determined
12.3⫾1.8
8.3⫾1.0
4.0⫾0.8
32
Improved
8.11⫾1.64
7.39⫾1.54
0.72⫾0.10
9
Not determined
Values are means ⫾ SD; n ⫽ no. of female (F) and/or male (M) subjects. ECHO, echocardiography; C, Caucasian; AA, African American; H, Hispanic; BMI,
body mass index; LV, left ventricular.
J Appl Physiol • VOL
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106 • JANUARY 2009 •
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below). Experimental approaches using obese pigs or primates may give better insight but are more expensive than
smaller obese rodents, which can prove unreliable (10, 11).
A guinea pig under current investigation (11) has an epicardial fat layer that sits astride the aortic arch and base of
the heart extending along epicardial coronaries in the atrioventricular grooves. In this model, the changes in EAT
resulting from obesity and its effects on the myocardium and
coronary arteries remain to be elucidated. The congenital
absence of EAT in humans does not prevent atherogenesis
(10). However, animal models of atherosclerosis might be
useful to determine if and how EAT contributes to the
progression of CAD once it has occurred.
In experienced hands, ECHO can reproducibly determine
maximal EAT thickness over the free wall of the RV (5, 6,
12), but it has several limitations as an index of EAT mass
(2, 3). EAT is a three-dimensional structure. ECHO measures EAT in two dimensions. EAT volume is more accurately quantitated at submillimeter resolution by CT (3) or
MRI (2). The ECHO detection limit is 1 mm (10), which
becomes important when differences between measurements
are of this order of magnitude (see Table 1). ECHO is
problematic if the region of interest is fat in the immediate
vicinity of the coronary artery. Although contiguous, pericoronary, and perimyocardial fat may not necessarily have
the same biochemical properties. Correlations between RV
EAT thickness measured by ECHO and the extent of CAD
are not a consistent finding (1) and can be challenged by a
recent report in which there was no relationship between
EAT volume or pericoronary fat thickness, both measured
by CT, and the severity of angiographically determined
CAD (4). Therefore, future human studies to assess whether
EAT is a CAD risk factor or contributes to CAD should
employ CT or MRI in conjunction with coronary angiography or intravascular ultrasound (IVUS) or perhaps coronary
magnetic resonance angiography (MRA) (3) because MRA
can simultaneously measure EAT volume, EAT thickness
over RV, EAT thickness around coronary arteries, and
atherosclerotic plaque burden.