Heart health risk: CR vs. weight loss

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Hi All,

The below paper appears to distinguish between the effects of weight loss and CR

on

cardiovascular risk. This may be summarized well in the concluding paragraph of

the

text:

" In summary, this study suggests a discordant effect of moderate body weight

loss on

reducing cardiovascular risk in obese patients, at least during energy

restriction.

Inflammatory markers such as CRP (20) and IL-6 (18) appear to be most sensitive

for

energy restriction, whereas the anti-inflammatory adiponectin and IL-10 are not

affected by a moderate weight decrease and might require prolonged periods of

energy-restricted diets to revert to normal. "

For definition, there is:

andromorphous: Having a male form or habitus. Synonym: android.

gynobase: A dilated base or receptacle, supporting a multilocular ovary.

morpho: Meaning form, shape, structure.

The pdf is available for the below.

Manigrasso MR, Ferroni P, Santilli F, Taraborelli T, Guagnano MT, Michetti N,

Davi

G.

Association Between Circulating Adiponectin and Interleukin-10 Levels in Android

Obesity. Effects of Weight Loss.

J Clin Endocrinol Metab. 2005 Jul 19; [Epub ahead of print]

PMID: 16030165

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve & db=pubmed & dopt=Abstra\

ct & list_uids=16030165 & query_hl=13

.... RESULTS

Baseline HOMA, BMI, WHR, and related measurements for the three groups of

subjects

are

summarized in Table 1. Only one of the obese women (in the android group) had a

BMI

of 28.1,

which is lower than 30, i.e. the commonly recommended cutoff for definition of

obesity (12). The

exclusion of this subject from the analysis did not significantly affect the

results. Baseline

median [iQR] levels of circulating adiponectin were significantly lower in 64

android vs. 20

gynoid obese and vs. 20 non-obese women (5.2 [3.3–7.8] vs. 12.1 [9.7–13.9] and

vs.

15.0 [12.6–

18.2] µg/mL, Kruskal-Wallis Test: H=40.2, p<0.0001) (Figure 1A). In addition, we

observed

significantly lower IL-10 levels in android vs. either gynoid or non-obese

healthy

women (1.8

[1.2–3.3] vs. 3.5 [2.9–4.3] and vs. 4.1 [3.5–4.8] pg/mL, H=35.1, p<0.0001),

whereas

IL-10 levels

of gynoid obese did not significantly differ from those observed in non-obese

women

(Figure 1B).

Table 1: Clinical characteristics of study participants

.........................................

----Non-obese n=20 Gynoid vs., non-obese p* Gynoid obese n=20 Gynoid vs.,

android p

Android obese n=64 Android vs., non-obese p

........................................

Age, years 46±11 NS 49±11 NS 49±14 NS

Body weight, Kg 69±6 <0.0001 86±10 NS 90±13 <0.0001

BMI 25.2±2.2 <0.0001 33.4±2.6 <0.01 37.1±5.3 <0.0001

Waist circumference, cm 94±5 NS 97±8 <0.0001 112±10 <0.0001

WHR 0.81±0.04 NS 0.81±0.03 <0.0001 0.96±0.06 <0.0001

Fasting insulin, µ U/ml 11.8±6.0 NS 13.2±5.5 <0.05 22.1±14.8 <0.01

HOMA 2.7±1.6 NS 3.0±1.4 <0.05 5.1±3.5 <0.01

...........................................

BMI: body mass index; WHR: waist-to-hip ratio; HOMA: homeostasis model

assessment.

*Bonferroni test for android vs., non-obese women

No correlation was observed between either adiponectin or Il-10 baseline levels

or

the

anthropometric measures in the non-obese group. Baseline IL-10 levels were

significantly

related to adiponectin concentrations (Rho=0.594, P<0.0001) among android, but

not

gynoid

obese women. No correlation was found between either adiponectin or IL-10 levels

and

HOMA

index. Univariate regression analysis of IL-10 predictor variables (age, WHR,

BMI,

HOMA

index and adiponectin levels) in all 84 obese women showed that WHR (Beta [sE]:

-0.20 [0.09],

p=0.02), HOMA index (Beta [sE]: 0.16 [0.08], p=0.05) and adiponectin levels

(Beta

[sE]: 0.67

[0.09], p< 0.0001) were all independently related to IL-10. Multivariate

analysis

performed by

backward stepping demonstrated that adiponectin (Beta [sE]: 0.72 [0.08], p<

0.0001)

was the

only variable independently associated to IL-10. Similar results were observed

in

the subgroup

of women with android, but not gynoid obesity (data not shown).

The effects of a short-term weight loss program on circulating adiponectin and

IL-10

levels were investigated in 15 android obese women. A median 8% decrease of BMI

was

observed in all 15 women, but a significant reduction of weight (from 113 [15]

to 95

[10] kg,

mean 8± 4 kg, p< 0.01) was achieved in 12 participants. Adiponectin and IL-10

were

analyzed before and after weight loss in all 15 patients according to an

intent-to-treat basis,

irrespectively of a successful reduction of body weight. HOMA index

significantly

decreased

by 17% (p< 0.02), whereas no significant changes either in adiponectin (median

percent

change 1%, ranging from –19 to 40%, p=0.23) or IL-10 levels (median percent

change

7.3,

ranging from –17 to 32%, p=0.99) were observed. Multivariate regression analysis

of

IL-10

predictor variables (age and percent changes of weight, HOMA index and

adiponectin

levels)

showed that adiponectin percent changes (Beta [sE]: 0.65 [0.24], p=0.017), but

not

HOMA

index (Beta [sE]: 0.48 [0.24], p=0.071) were independently related to IL-10

percent

changes.

DISCUSSION

A transcriptional mechanism leading to decreased adiponectin plasma levels in

obese

women

has been previously demonstrated and low levels of adiponectin have been

associated

with high

levels of CRP and IL-6 (13). To our knowledge, this is the first study

demonstrating

that android,

but not gynoid obesity is associated with a down-regulation of circulating

IL-10,

and that low

adiponectin concentrations are independently related to decreased IL-10 levels

in

women with

android obesity, independently of insulin resistance. Based on these results, we

hypothesize that

adiponectin might modulate the anti-inflammatory response through IL-10

expression,

as recently

suggested in in vitro models of human monocyte-derived macrophages (5, 14).

The finding of decreased IL-10 levels in android obese women looks controversial

to

previously published data that showed higher IL-10 levels in obese women

compared to

normal

weight individuals (15). However, we must consider that one of the exclusion

criteria of our

study was the presence of metabolic syndrome, and our obese subjects were

otherwise

healthy,

whereas in the cited study both obese and non-obese groups included women with

metabolic

syndrome or one or more cardiovascular risk factors (15). Furthermore, Esposito

et

al. performed

no comparative analysis between android and gynoid obesity (15). In the present

study, we found

no difference in IL-10 levels between gynoid obese and non-obese women, whereas

low

IL-10

levels were significantly associated to an increased WHR, suggesting that

different

fat

distribution might be responsible for decreased levels of this cytokine. Thus,

differences in the

populations recruited and design of the studies may explain an apparent

discrepancy

between the

two studies.

IL-10 exerts multifaceted anti-inflammatory properties, and its reduction may

favor

the

progression of atheromatous lesions toward a vulnerable phenotype (16).

Adiponectin

may

also have anti-atherogenic and anti-inflammatory properties, and high

circulating

levels of

both proteins have been related to a lower risk of coronary heart disease (16).

Since these

factors may be regulated by adipocytes and/or adipose tissue, it seems

reasonable to

expect

that weight loss programs might have favorable effects. However, our data do not

support

this and are in agreement with recent reports indicating that moderate weight

loss

(17) did not

result in a change in plasma adiponectin concentrations. In contrast, Esposito

et

al. reported

that a long-term program of body weight reduction was capable of increasing

adiponectin

concentrations (18). However, it should be noticed that in the latter study a

weight

reduction

by 10% or more maintained for 2 years was required for inclusion, whereas in

others

(17) and

our study a reduction of approximately 8 Kg was achieved over a 12-week period.

Moreover,

in the study by Esposito et al. (18) adiponectin concentrations were

significantly

increased in

obese individuals who had lost a mean of 14 kg, but not in subjects who had lost

a

mean of 3

kg. These considerations suggest that changes in plasma adiponectin may not

become

apparent until substantial amounts of weight have been lost.

Our results also indicated that substantial improvements in insulin sensitivity

(assessed

by HOMA index) after moderate weight loss were not associated with an increase

in

plasma

adiponectin concentration in android obese women. Because there is ample

evidence

that

insulin resistance is attenuated with this degree of weight loss (19), our

findings

imply that

changes in circulating adiponectin may not mediate weight loss-induced

improvements

in

insulin sensitivity. These data differ from those when much greater amounts of

weight are

lost (18) but are consistent with the findings by Abbasi et al., who showed that

moderate

weight loss in obese women was not associated with an increase in plasma

adiponectin

concentration either in insulin-sensitive or insulin-resistant individuals (17).

Plasma IL-10 levels did not show any significant change after moderate weight

loss,

which is in agreement with the finding that a lifestyle change program was

unable to

substantially modify IL-10 levels in obese women with metabolic syndrome (15).

The

significant association observed between the percent changes of IL-10 and

adiponectin after

diet could be biased by the minimal variation observed and the limited number of

subjects,

and do not allow any conclusion at this time. However, the independent

association

of

adiponectin and IL-10 levels at multivariate analysis is suggestive for their

close

relationship.

In summary, this study suggests a discordant effect of moderate body weight loss

on

reducing cardiovascular risk in obese patients, at least during energy

restriction.

Inflammatory markers such as CRP (20) and IL-6 (18) appear to be most sensitive

for

energy

restriction, whereas the anti-inflammatory adiponectin and IL-10 are not

affected by

a

moderate weight decrease and might require prolonged periods of

energy-restricted

diets to

revert to normal.

Al Pater, PhD; email: old542000@...

____________________________________________________

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