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Higher baseline irisin concentrations are associated with greater reductions in glycemia and insulinemia after weight loss in obese subjects

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Irisin is assumed to be a relevant link between muscle and weight maintenance as well as to mediate exercise benefits on health. The aim of this study was to assess the possible associations between irisin levels and glucose homeostasis in obese subjects with metabolic syndrome (MetS) following an energy-restricted treatment. Ninety-six adults with excessive body weight and MetS features underwent a hypocaloric dietary pattern for 8 weeks, within the RESMENA randomized controlled trial (www.clinicaltrials.gov; NCT01087086). After the intervention, dietary restriction significantly reduced body weight and evidenced a dietary-induced decrease in circulating levels of irisin in parallel with improvements on glucose homeostasis markers. Interestingly, participants with higher irisin values at baseline (above the median) showed a greater reduction on glucose (P=0.022) and insulin (P=0.021) concentrations as well as on the homeostasis model assessment index (P=0.008) and triglycerides (P=0.006) after the dietary intervention, compared with those presenting low-irisin baseline values (below the median). Interestingly, a positive correlation between irisin and carbohydrate intake was found at the end of the experimental period. In conclusion, irisin appears to be involved in glucose metabolism regulation after a dietary-induced weight loss.
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SHORT COMMUNICATION
Higher baseline irisin concentrations are associated with greater
reductions in glycemia and insulinemia after weight loss
in obese subjects
P Lopez-Legarrea
1,2
, R de la Iglesia
1
, AB Crujeiras
3,4,5
, M Pardo
3,4
, FF Casanueva
4
, MA Zulet
1,3
and JA Martinez
1,3
Irisin is assumed to be a relevant link between muscle and weight maintenance as well as to mediate exercise benefits on health.
The aim of this study was to assess the possible associations between irisin levels and glucose homeostasis in obese subjects
with metabolic syndrome (MetS) following an energy-restricted treatment. Ninety-six adults with excessive body weight
and MetS features underwent a hypocaloric dietary pattern for 8 weeks, within the RESMENA randomized controlled trial
(www.clinicaltrials.gov; NCT01087086). After the intervention, dietary restriction significantly reduced body weight and evidenced a
dietary-induced decrease in circulating levels of irisin in parallel with improvements on glucose homeostasis markers. Interestingly,
participants with higher irisin values at baseline (above the median) showed a greater reduction on glucose (P¼0.022) and insulin
(P¼0.021) concentrations as well as on the homeostasis model assessment index (P¼0.008) and triglycerides (P¼0.006) after
the dietary intervention, compared with those presenting low-irisin baseline values (below the median). Interestingly, a positive
correlation between irisin and carbohydrate intake was found at the end of the experimental period. In conclusion, irisin appears to
be involved in glucose metabolism regulation after a dietary-induced weight loss.
Nutrition & Diabetes (2014) 4, e110; doi:10.1038/nutd.2014.7; published online 24 February 2014
INTRODUCTION
Obesity is a worldwide health burden, accompanied by a number
of comorbidities including glucose intolerance, insulin resistance
and type 2 diabetes.
1
In this context, the myokine irisin,
2
which is a
cleavage product of the type I membrane protein fibronectin type
III domain-containing 5, has been hypothesized as a target to
counteract obesity and type 2 diabetes.
3,4
Irisin is expressed in the
muscle and the adipose tissue and has been associated with
adiposity and body weight in animals
5,6
and humans.
7,8
However,
the precise role and underlying mechanisms concerning irisin
actions and signaling pathways remain incompletely understood.
The aim of this research was to assess changes on circulating
irisin concentrations in obese subjects presenting metabolic
syndrome (MetS) features after a treatment designed to lose
weight and to analyze the potential relationships of this myokine
with glucose homeostasis after dieting.
MATERIALS AND METHODS
Study protocol
This research reports the findings of the 8-week intervention period of
the RESMENA randomized intervention trial (www.clinicaltrials.gov;
NCT01087086), which was conducted following the CONSORT 2010
criteria. A full list of inclusion criteria, as well as a complete description
of the study methodology can be found in earlier publications.
9,10
Briefly,
participants were randomized into two intervention groups, with the same
energy restriction (–30% E), but differing mainly in the carbohydrate/
protein ratio and meal frequency: control group supplying 55% E from
CHO and 15% E from proteins within a 3–5 meals per day pattern,
and RESMENA group providing 40% E from CHO and 30% E from proteins
within a 7 meals per day plan.
Subjects
Ninety-six adults (mean age ¼50 years old; range 21–70 years old)
with excessive body weight (mean body mass index ¼35.9 kg m
–2
; range
26.9–49.4 kg m
–2
) suffering MetS according to the International Diabetes
Federation criteria completed the intervention period. All the participants
gave a written informed consent to participate as approved by the Ethics
Committee of the University of Navarra (065/2009) and in accordance with
the Declaration of Helsinki.
Participant’s dietary intake was assessed by means of 48-h weighed
records at baseline and at the end of the intervention and further analyzed
using the DIAL software (Alce Ingenieria, Madrid, Spain). Subjects were
asked to maintain their usual activity levels during the study, which was
monitored at the beginning and endpoint with a validated 24-h physical
activity questionnaire.
9
Anthropometric measurements and body composition determinations
were performed, as described elsewhere.
9
Overnight fasting plasma levels
of glucose and triglycerides were measured in an autoanalyzer Pentra
C-200 (HORIBA ABX, Madrid, Spain) with specific kits from this company.
Insulin concentrations were determined with an enzyme-linked
immunosorbent assay kit (Mercodia, Uppsala, Sweden) in a Triturus
autoanalyzer (Grifols SA, Barcelona, Spain) and the homeostasis model
(homeostatic model assessment-insulin resistance (HOMA-IR)) was applied
to estimate insulin resistance.
Irisin plasma levels were determined using a commercial enzyme-linked
immunosorbent assay kit following the manufacturer’s instructions (Irisin
ELISA kit EK-067–52; Phoenix Pharmaceuticals, Inc., Burlingame, CA, USA),
1
Department of Nutrition, Food Science and Physiology, University of Navarra, Pamplona, Spain;
2
Faculty of Health Science, Universidad Autonoma de Chile, Santiago, Chile;
3
CIBERObn, Carlos III Health Institute, Madrid, Spain;
4
Laboratory of Molecular and Cellular Endocrinology, Health Research Institute (IDIS), University of Santiago Hospital Complex
(CHUS) and Santiago de Compostela University (USC), Santiago de Compostela, Spain and
5
Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute
(IDIBELL), Barcelona, Spain. Correspondence: Professor JA Martinez, Department of Nutrition, Food Science and Physiology, University of Navarra, C/Irunlarrea 1, Pamplona 31008,
Spain.
E-mail: jalfmtz@unav.es
Received 5 September 2013; revised 4 January 2014; accepted 18 January 2014
Citation: Nutrition & Diabetes (2014) 4, e110; doi:10.1038/nutd.2014.7
&
2014 Macmillan Publishers Limited All rights reserved 2044-4052/14
www.nature.com/nutd
on a spectrophotometric reader at a wavelength of 450 nm (Versamax
Microplate Reader, East Falmouth, MA, USA). This test provided a range of
detection of 0.066–1024ng ml
–1
and exhibited a coefficient of variation of
6–10% inter- and intra-assay. The samples were kept at 80 1C and were
analyzed immediately after the experiment was ended.
Statistical analysis
The sample size of this secondary analysis was calculated for an a¼0.05
and a power of 80% based on the waist circumference reduction, as
described elsewhere.
9
Normality distributions of the measured variables
were determined according to the Shapiro–Wilk test. Irisin plasma levels
were not normally distributed, but based on the sample size (n460) a
parametric test was performed. Indeed, after analysis with a log
transformation of irisin values the statistical outcomes were maintained.
Differences between baseline and endpoint values within groups were
analyzed by a paired t-test. Analyses between dietary groups were
performed with unpaired t-tests. A multiple linear regression analysis was
applied in order to assess the potential relationships among irisin with
anthropometric and biochemical measurements (95% confidence interval).
The median value of irisin baseline concentrations was considered as the
cutoff for analyzing the effect of high- or low-irisin levels on glucose
regulatory factors, as previously applied.
11
This tool is based on the
assignment of the studied population into two groups of disease risk. The
association between irisin levels and carbohydrate intake was assessed
using the parametric Pearson correlation. Specific statistical analyses
(analysis of covariance) were performed after excluding outlier values in
order to control the regression to the mean phenomenon. Statistical
analysis was performed using SPSS15.1 software (SPSS Inc., Chicago, IL,
USA). An alpha level of 0.05 was set up for determining statistically
significant differences. Data are reported as mean±s.e.
RESULTS
At the beginning of the intervention, there were no differences
between groups in any of the anthropometric and routine
biochemical markers (P40.05). After the intervention, an improve-
ment (reduction) was observed on these measurements with
apparently equal effectiveness between the two dietary treat-
ments (P40.05, Table 1), except for adiponectin, which was
increased in both groups, but without reaching statistical
significance. Changes in irisin concentrations were similar
(P40.05) in the control group ( 87.3±18.4 ng ml
–1
) as compared
with the RESMENA group ( 59.8±11.8 ng ml
–1
), after following
the energy-restricted treatment. Therefore, both groups were
merged for subsequent analyses. Considering the whole sample,
participant’s mean body weight loss was 6.9±3.0 kg and irisin
plasma concentrations diminished (Figure 1a) in association with
changes in body weight (r¼0.21; P¼0.046) and fat mass (r¼0.22;
P¼0.037). As the main objective of this study was to evaluate the
potential role of irisin on glucose homeostasis and given that
some of the participants were diabetic, a preliminary analysis
separating non-diabetic and diabetic participants was also
performed. Differences were found for glucose concentrations
and HOMA index between both groups after the nutritional
intervention with energy restriction, but similar outcomes were
found concerning irisin concentrations (data not shown).
Similar values were found concerning physical activity assess-
ments at the beginning and at the end of the intervention in both
dietary groups. Moreover, the regression analysis showed no
relationships between physical activity factor and irisin levels
changes (P¼0.736). An association of circulating glucose
(B¼0.134, 95% confidence interval: 0.245 to 0.024;
P¼0.018) and irisin concentrations changes was found, irrespec-
tive of confounding factors: gender, age, diet, body weight loss
and irisin baseline values.
Interestingly, after adjusting for gender, age and weight loss,
participants belonging to the high-irisin group at baseline
(4308.0 ng ml
–1
) evidenced significantly greater reductions
(Figure 1b) on glucose (P¼0.022), insulin (P¼0.021), HOMA index
(P¼0.008) and triglycerides (P¼0.006), compared with those
belonging to the low-irisin group at baseline (o308.0 ng ml
–1
).
Furthermore, the decrease in irisin concentrations was signifi-
cantly greater (Po0.001) within the group with high-irisin values
at baseline ( 126.6±15.9 ng ml
–1
) than within the lower
irisenemia group ( 18.2±9.1 ng ml
–1
). After 8 weeks of nutri-
tional intervention, irisin concentrations were positively correlated
with carbohydrate intake (cereals, pulse, fruits and vegetables;
r¼0.234, P¼0.023; Figure 1c).
DISCUSSION
This study evidenced that irisin per se may exert an effect on the
reduction of glucose, insulin and triglycerides concentrations after
prescribing an 8-week nutritional intervention to obese subjects
with MetS traits.
Irisin is a recently discovered muscle-derived hormone, whose
secretion is induced by exercise.
2
This myokine has been shown to
be able to increase energy expenditure, and therefore, it has been
proposed to have a potential role in obesity and diabetes
treatments.
2,12–14
Since discovery, a number of original studies
have addressed various aspects of the biology of irisin.
15
However,
the regulation and specific role of irisin in human’s glucose
metabolism remain still unclear. Thus, the main objective of the
current research was to investigate the potential relationships
between irisin concentrations and glucose homeostasis, after
dieting.
Table 1. Changes in selected anthropometric and biochemical parameters within each dietary group (control and RESMENA) after the 8-week
intervention and comparison between groups
Control group RESMENA group Difference between diet
groups (P-value)
Baseline Endpoint P-value Baseline Endpoint P-value
Body weight (kg) 99.5±2.8 92.7±2.7 o0.001 100.0±2.4 92.9±2.3 o0.001 0.555
BMI (kg m
–2
) 36.2±0.7 33.7±0.7 o0.001 35.6±0.6 33.0±0.6 o0.001 0.732
Fat mass (%) 39.1±1.1 36.2±1.1 o0.001 39.2±0.9 36.4±1.0 o0.001 0.854
Fat mass (kg) 39.0±1.6 33.7±1.5 o0.001 39.2±1.4 33.8±1.3 o0.001 0.886
Glucose (mg dl
–1
) 121.0±5.0 108.0±2.0 0.006 123.8±5.5 110.2±3.8 0.016 0.939
Insulin (mUml
–1
) 15.3±1.7 9.3±1.1 o0.001 14.4±1.2 9.1±0.9 o0.001 0.557
HOMA 4.7±0.6 2.6±0.3 o0.001 4.5±0.4 2.6±0.3 o0.001 0.686
Triglycerides (mg dl
–1
) 176±13 145±10 0.005 194±18 151±14 o0.001 0.421
Irisin (ng ml
–1
) 412.3±31.6 326.7±22.6 o0.001 299.4±16.3 239.6±8.8 o0.001 0.234
Leptin (ng ml
–1
) 22.4±2.3 14.8±1.8 o0.001 20.2±2.1 12.8±1.6 o0.001 0.883
Adiponectin (ng ml
–1
) 13.6±1.5 13.8±1.3 0.863 12.1±1.3 17.6±3.3 0.127 0.152
Abbreviations: BMI, body mass index; HOMA, homeostasis model assessment.
Irisin and glucose homeostasis
P Lopez-Legarrea et al
2
Nutrition & Diabetes (2014), 1 – 4 &2014 Macmillan Publishers Limited
The study was designed as a randomized controlled nutritional
intervention comparing two energy-restricted dietary treatments.
9
Both control and RESMENA dietary strategies proved to be
effective for improving MetS disturbances by lowering
anthropometric and biochemical markers, being these outcomes
in agreement with other studies concerning hypocaloric diets.
16
However, no differences between treatments were observed for
any of the studied variables including irisin. For that reason, the
sample was merged and considered as a whole for the
subsequent analyses regarding irisin concentrations and its
potential associations with glucose metabolism.
First, changes on irisin concentrations after the 8 weeks of
nutritional intervention were evaluated. This study evidenced that
irisin plasma concentrations decreased after the energy restriction
program and the subsequent weight loss, independently of the
dietary group. This finding is in agreement with a previous study
that reported a reduction in irisin levels after surgically induced
weight markdown.
8
Then, the potential role of irisin on glucose homeostasis-related
parameters was analyzed in order to reach the main objective of
the research. The prime finding of the current investigation was
that higher irisin concentrations at the beginning of the
intervention were associated with greater reductions on glucose
and insulin concentrations as well as on the HOMA index,
independently of body weight loss. Although this outcome should
be carefully examined, similar results have been reported in
children by Al-Daghri et al.
17
where a crucial role for irisin in
glucose homeostasis was suggested. On the other hand, those
individuals with higher irisin concentrations at the beginning of
the intervention also achieved higher beneficial effects regarding
the lowering of triglycerides concentrations. This effect could be
explained by the fact that triglycerides levels have been revealed
to positively correlate with glucose levels.
18
Thus, the effects of
irisin on the changes of glucose concentrations may have been
subsequently reflected on triglycerides. In addition, taking into
account that irisin has been evidenced to increase energy
expenditure,
19
the greater reduction observed in triglycerides
according to the high-irisin levels at baseline may be also due to a
higher utilization of triglycerides as energy substrate. Previous
studies have also evidenced an inverse association of irisin levels
with triglycerides concentrations.
20
Taking together these
outcomes, it can be suggested that irisin may be involved in the
regulation of glucose homeostasis in obese subjects presenting
MetS features. Thus, irisin could mean a physiological feedback to
counteract potential glucose metabolism-related disturbances
associated to an excessive body weight state. Irisin would seem
to be increased in unfavorable metabolic situations acting as a
compensatory triggering mechanism. Other authors have likewise
claimed that the increase in irisin under obesity conditions may
indicate a physiological adaptation to improve glucose tolerance,
which is often impaired in obese subjects.
3
Indeed, this behavior
has been observed predominantly in individuals with metabolic
disease
21
as it is the condition of our study population. However,
other studies reported associations between plasma irisin levels
and important metabolic factors in non-diabetic subjects, but not
in individuals with type 2 diabetes.
4,22
Our suggested corollary
would be that irisin is increased in metabolically altered situations
and may diminish as a consequence of the weight loss, as irisin is
then ‘less’ needed to restore the altered metabolic state. Thus, the
theory about a possible irisin resistance appears similar to the
well-known leptin insensitivity in obesity and cannot be
discarded
21
as has been reported for leptinemia and insulinemia
after dieting.
11
The association between irisin concentrations and carbohydrate
intake was related to the consumption of some sources of
carbohydrates (cereals, pulse, fruits and vegetables). This outcome
may be explained because the dietary modifications during the
hypocaloric intervention evolved with shifts in carbohydrate
consumption within the energy restriction. Thus, irisin could be
increased in response to the dietary pattern, depending on the
carbohydrate content, in order to prevent/improve the rise on
glucose, insulin or HOMA index values, linked to latter damage on
multiple organs.
23
This finding is interesting given that modifying
the macronutrient distribution is a recurrent approach for treating
obese and MetS patients.
24
The observed results appear to be irrespective to the physical
activity, as patients in this study maintained the same physical
activity level along the intervention. The statistical adjustments for
sex did not revealed specific differences between males and
females concerning the analyzed irisin outcomes. A limitation of
this study is that it demonstrated an association but not evidenced
causation. Moreover, the methods to assess the dietary intake and
physical activity were based on questionnaires, which could bias the
results interpretation. Also, some other relevant measurements in
relation to glucose metabolism, such as OGTT or Clamp-test would
be appropriate. However, the design of the current trial based on a
Figure 1. Irisin changes from baseline (week 0) to the end (week 8)
of the intervention (a); changes in glucose, insulin, HOMA index and
triglycerides, depending on irisin baseline levels after the interven-
tion of 8 weeks duration (b); and irisin correlation with carbohydrate
intake (cereals, pulse, fruits and vegetables) at the endpoint of the
intervention (c).
Irisin and glucose homeostasis
P Lopez-Legarrea et al
3
&2014 Macmillan Publishers Limited Nutrition & Diabetes (2014), 1 – 4
nutritional intervention involving a quite large human sample is
indeed a valuable feature enabling pre- and post-test comparisons
within subjects. An effect of regression to the mean could not be
attributed since pertinent statistical procedures were performed in
order to control this phenomenon.
This research concerns the investigation of a potential role of
irisin on impaired glucose homeostasis associated to obesity and,
consequently, the metabolic interplay on glucose metabolism and
insulin secretion control. Indeed, the search of predictive
laboratory markers is of value for clinical practice.
CONFLICT OF INTEREST
The authors declare no conflict of interest.
ACKNOWLEDGEMENTS
This work was supported by the Government of Navarra (48/2009), the LE
Nutrition, Obesity and Health (University of Navarra LE/97) and CIBERobn/RETICS,
ISCIII initiatives. PL-L is funded by the Government of Navarra (233/2009) and ABC
and MP by the ISCIII (Sara Borrell C09/00365 and Miguel Servet schemes). This
research is collaborative study of the CIBERobn program on Fisiopatologia de la
Obesidad y la Nutricion funded by the Institute Carlos III of the Spanish Ministry of
Health, Madrid.
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Irisin and glucose homeostasis
P Lopez-Legarrea et al
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Nutrition & Diabetes (2014), 1 – 4 &2014 Macmillan Publishers Limited
... A possible explanation for this phenomenon and integrating the other reported evidence may be that irisin levels can increase in the context of adverse metabolic states to ameliorate the detrimental consequences of these conditions, including vascular damage. This compensatory mechanism, as explained previously, is acknowledged as irisin resistance, suggesting that irisin levels may be associated with several cardiometabolic risk variables due to an underlying corrective secretion by adipose or skeletal muscle tissue [22,96]. As a result, in states of abnormal compensation or reduced irisin sensitivity, the protective role of irisin is lost. ...
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Endothelial dysfunction is a crucial physiopathological mechanism for cardiovascular diseases that results from the harmful impact of metabolic disorders. Irisin, a recently discovered adipomyokine, has been shown to exert beneficial metabolic effects by increasing energy consumption, improving insulin sensitivity, and reducing the proinflammatory milieu. Multiple preclinical models have assessed irisin's possible role in the development of endothelial dysfunction, displaying that treatment with exogenous irisin can decrease the production of oxidative stress mediators by up-regulating Akt/mTOR/Nrf2 pathway, promote endothelial-dependent vasodilatation through the activation of AMPK-PI3K-Akt-eNOS pathway, and increase the endothelial cell viability by activation of ERK proliferation pathway and downregulation of Bad/Bax/Caspase 3 pro-apoptotic pathway. However, there is scarce evidence of these mechanisms in clinical studies, and available results are controversial. Some have shown negative correlations of irisin levels with the burden of coronary atherosclerosis and leukocyte adhesion molecules' expression. Others have demonstrated associations between irisin levels with increased atherosclerosis risk and higher carotid intima-media thickness. Since the role of irisin in endothelial damage remains unclear, in this review, we compare, contrast, and integrate the current knowledge from preclinical and clinical studies to elucidate the potential preventive role and the underlying mechanisms and pathways of irisin in endothelial dysfunction. This review also comprises original figures to illustrate these mechanisms.
... Serum irisin can reflect the metabolic status (4). In addition, it has been demonstrated that serum-circulating irisin levels are associated with significantly increased fibronectin type III domain protein 5 (FNDC5) gene expression in adipose tissue (5,6). The expression of FNDC5 in fat is approximately 1/100 of that in muscle (7). ...
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Objective The present research aimed to study the relationship between body mass index (BMI), sex hormones, leptin, and irisin in children and adolescents with different body types. Methods In this study, a stratified cluster random sampling method was used to select students aged 8-15 years from two 9-year schools as the research subjects. Based on a case-control study, 183 overweight/obese students were selected. After using sex and age matching to create a matched sample of normal-weighted students, a total of 366 students, including 214 boys (58.5%) and 152 girls (41.5%) were included. We measured their height and weight and calculated their body mass index BMI. Afterward, their concentrations of leptin, irisin, oestradiol (E2), and testosterone (T) in the serum were detected. Results There were significant differences in T, E2, leptin, and irisin between normal-weighted boys and girls ( p < 0.05). There were statistically significant differences in T, E2, and irisin between overweight/obese boys and girls ( p < 0.05). Overweight/obese students had higher concentrations of irisin and leptin than normal-weight students (p < 0.05). The direct effect of BMI on irisin was not statistically significant in either normal or overweight/obese students, but their indirect effects via leptin were statistically significant (for normal-weight boys and girls, standardized indirect effect coefficient: 0.29 and 0.38, respectively; for overweight/obese boys and girls, standardized indirect effect coefficient: 0.36 and 0.34, respectively). There was a negative pathway of E2 → leptin → irisin in normal-weight boys (standardized indirect effect coefficient: −0.24) and a negative pathway of T → leptin → irisin in overweight/obese boys (standardized indirect effect coefficient: −0.27). Conclusion The indirect effects of BMI on irisin via leptin exist in children and adolescents of different body types. E2 was negatively correlated with leptin in normal-weight boys, whereas T was negatively correlated with leptin in overweight/obese boys.
... Dietary intervention is another effective way to reduce body adipose tissue by reducing energy intake. Lopez-Legarre et al. demonstrated that following 8 weeks of lowenergy dietary intervention, the weights of patients who were overweight and those with metabolic syndromes decreased significantly, and the levels of IRISIN circulating in their blood were significantly reduced (42). However, animal experiments have shown that after 3 months of energy restriction, Fndc5 and Ucp1 levels in the WAT of rats increased significantly (43), suggesting that dietary control could promote WAT beigeization. ...
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... 26 In a study by Lopez-Legarrea et al., it has been shown that irisin is decreased after the weight loss program since it is needed less to improve the altered metabolism. 27 Similarly, in the study of Crujeiras et al., a significant decrease was observed in the irisin levels after the hypocaloric diet programme and they concluded that irisin levels demonstrated the body fat mass and that irisin levels were modified according to the adiposity level of the body. 23 Conversely, we found a significant increase in irisin levels at 32 nd weeks. ...
... Harcanandan fazla enerji alımı sonucu insülin direnci ve viseral obezite ile bağlantılı olarak irisin seviyesinin yükseldiği belirlenmiştir (Gavrieli & Mantzoros, 2016). Obez bireylerde 8 hafta boyunca farklı makro besin ögesi oranları içeren ancak enerji kısıtlı diyet uygulamaları sonucu özellikle diyetin karbonhidrat kaynağının tam tahıllı ürünler, meyve ve sebze olduğu grupta irisin seviyesinin anlamlı düzeyde düştüğü saptanmıştır (Lopez-Legarrea et al., 2014). Deney hayvanlarında uygulanan yüksek ve düşük yağlı diyetin irisin seviyesini iki grupta da anlamlı olarak değiştirmediği belirlenmiştir (Gavrieli & Mantzoros, 2016). ...
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... Also positive association of irisin concentration and HOMA-IR, fasting insulin and blood glucose levels were reported in some studies. Studies have shown that insulin resistance is positively associated with serum irisin concentration (41,42). In other study, it is reported that children with impaired glucose tolerance, had higher circulating irisin levels (43). ...
... However, in contrast with the above reports, several other studies question the beneficial role of irisin and in some cases even its existence (101)(102)(103)(104). There is also a disagreement regarding the induction of FNDC5/irisin by exercise (105,106), and its association with markers of glucose and lipid homeostasis disturbance in obesity and metabolic syndrome (107)(108)(109)(110). Such controversies could be explained by the fact that irisin levels increase only when muscle ATP concentration decreased in absence of physical activity during sedentary lifestyle (105). ...
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Irisin, a novel myokine, increases energy expenditure and glucose tolerance and, thus, improves carbohydrate homeostasis in humans. This hormone has potential therapeutic applications for weight loss and improvement of insulin resistance in subjects with obesity and diabetes mellitus type 2 (T2DM). In this cross-sectional study we aimed to associate circulating levels of irisin and several anthropometric and metabolic parameters among Arab children. A cohort of 153 Saudi children [81 boys age: 12.4±3.2y; BMI: 19.5±5.9 kg/m(2) ] and 72 girls: [age: 12.9±3.2y; BMI: 20.6±5.2], were examined. Anthropometry was obtained and fasted bloods were collected for biochemical analyses. Irisin was assessed by a specific enzyme-linked immunosorbent assay (ELISA). Girls had higher circulating irisin levels than boys (p=0.04). There were several significant correlations between circulating irisin and fasting blood glucose (FBG) (r= -0.35, p<0.001), sagital abdominal diameter (SAD) (r=-0.34, p<0.001) and HDL cholesterol (r=0.17, p=0.04) across the entire cohort studied. Notably in girls, but not in boys, HOMA-IR correlated negatively with irisin levels (r=-0.32, p=0.02), as previously noted in adults. FBG was a significant predictor of circulating irisin (R(2) =0.16) followed by SAD. In multivariate linear regression analysis, after controlling for potential confounders such as gender, age, and BMI, irisin levels were independently associated with FBG (β=-0.34, p=0.01), particularly in girls. Serum irisin levels were higher in girls than in boys and correlated negatively with HOMA-IR. They were also independently associated with FBG predominantly in girls, suggesting that this hormone may play a crucial role in glucose metabolism from an early age. This article is protected by copyright. All rights reserved.
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Context: Irisin, a recently identified hormone, has been proposed to regulate energy homeostasis and obesity in mice. Whether irisin levels are associated with risk of the metabolic syndrome (MetS), cardiometabolic variables, and cardiovascular disease (CVD) risk in humans remains unknown. Objective: Our objective was to assess the associations between baseline serum irisin levels and MetS, cardiometabolic variables, and CVD risk. Design, setting, and subjects: We conducted a comparative cross-sectional evaluation of baseline circulating levels of the novel hormone irisin and the established adipokine adiponectin with MetS, cardiometabolic variables, and CVD risk in a sample of 151 subjects. Results: Baseline irisin levels were significantly higher in subjects with MetS than in subjects without MetS. Irisin was associated negatively with adiponectin (r = -0.4, P < .001) and positively with body mass index (r = 0.22, P = .008), systolic (r = 0.17, P = .04) and diastolic (r = 0.27, P = .001) blood pressure, fasting glucose (r = 0.25, P = .002), triglycerides (r = 0.25, P = .003), and homeostasis model assessment for insulin resistance (r = 0.33, P < .001). After adjustment for potential confounders, including body mass index, subjects in the highest tertile of irisin levels were more likely to have MetS (odds ratio [OR] = 9.44, 95% confidence interval [CI] = 2.66-33.44), elevated fasting blood glucose (OR = 5.80, 95% CI = 1.72-19.60), high triglycerides (OR = 3.89, 95% CI = 1.16-13.03), and low high-density lipoprotein cholesterol (OR = 3.30, 95% CI = 1.18-9.20). Irisin was independently associated with homeostasis model assessment for insulin resistance and general Framingham risk profile in multiple linear regression analyses after adjustment for confounders. Adiponectin demonstrated the expected associations with outcomes. Conclusions: Irisin is associated with increased risk of MetS, cardiometabolic variables, and CVD in humans, indicating either increased secretion by adipose/muscle tissue and/or a compensatory increase of irisin to overcome an underlying irisin resistance in these subjects.
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Background & aims: Obesity is closely related to non-alcoholic fatty liver disease (NAFLD), which has become an important public health problem because of its high prevalence and association with metabolic syndromes. Irisin was recently identified as a novel peptide to improve obesity and glucose homeostasis, and considered to be therapeutic for human metabolic diseases. The aim of this study was to examine the association of serum irisin concentration and liver triglyceride contents in obese Chinese adults. Methods: Serum irisin levels were measured and liver fat contents determined by (1)H MRS in 296 obese adults. Anthropometric parameters and blood biochemical indexes including liver enzymes, glucose, and lipid profiles were detected. The liver triglyceride contents of subjects were measured by (1)H MRS. The protein levels of irisin were determined by quantitative ELISA. Results: We found that serum irisin levels were reduced in obese adults with NAFLD. By dividing the distribution of intrahepatic triglyceride (IHTG) contents into quartiles, serum irisin levels were reduced gradually with the increase of IHTG contents (p<0.01). Higher serum irisin levels were associated with preferable TG levels. Serum ALT and AST concentrations were inversely correlated with serum irisin levels. Multivariate linear regression analysis demonstrated that serum irisin levels were independently associated with liver fat (p<0.01). By logistic regression analysis, the odds ratio for higher IHTG contents was reduced by 12.4% per 1 SD increase in serum irisin concentrations after adjustment for multivariate metabolic factors [OR (95% CI); 0.876 (0.777-0.987)]. Conclusions: These results demonstrated that serum irisin concentrations were inversely associated with the triglyceride contents in the liver and liver enzymes in obese Chinese adults.