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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 (; 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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Higher baseline irisin concentrations are associated with greater
reductions in glycemia and insulinemia after weight loss
in obese subjects
P Lopez-Legarrea
, R de la Iglesia
, AB Crujeiras
, M Pardo
, FF Casanueva
, MA Zulet
and JA Martinez
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
(; 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
Obesity is a worldwide health burden, accompanied by a number
of comorbidities including glucose intolerance, insulin resistance
and type 2 diabetes.
In this context, the myokine irisin,
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.
Irisin is expressed in the
muscle and the adipose tissue and has been associated with
adiposity and body weight in animals
and humans.
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.
Study protocol
This research reports the findings of the 8-week intervention period of
the RESMENA randomized intervention trial (;
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.
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.
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
; range
26.9–49.4 kg m
) 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.
Anthropometric measurements and body composition determinations
were performed, as described elsewhere.
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),
Department of Nutrition, Food Science and Physiology, University of Navarra, Pamplona, Spain;
Faculty of Health Science, Universidad Autonoma de Chile, Santiago, Chile;
CIBERObn, Carlos III Health Institute, Madrid, Spain;
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
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,
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
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
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.
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.
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.
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
) as compared
with the RESMENA group ( 59.8±11.8 ng ml
), 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
) 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
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
) than within the lower
irisenemia group ( 18.2±9.1 ng ml
). 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).
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.
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
Since discovery, a number of original studies
have addressed various aspects of the biology of irisin.
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
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
) 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
) 121.0±5.0 108.0±2.0 0.006 123.8±5.5 110.2±3.8 0.016 0.939
Insulin (mUml
) 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
) 176±13 145±10 0.005 194±18 151±14 o0.001 0.421
Irisin (ng ml
) 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
) 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
) 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
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.
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.
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.
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.
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.
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
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.
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.
Indeed, this behavior
has been observed predominantly in individuals with metabolic
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.
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
as has been reported for leptinemia and insulinemia
after dieting.
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.
This finding is interesting given that modifying
the macronutrient distribution is a recurrent approach for treating
obese and MetS patients.
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
&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.
The authors declare no conflict of interest.
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
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. ...
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). ...
Full-text available
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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Background: Obesity is a growing problem worldwide, and newer therapeutic strategies to combat it are urgently required. This study aimed to analyze the effect of diet and exercise interventions on energy balance in mice and elucidate the mechanism of the peroxisome proliferator-activated receptor-gamma co-activator-1-alpha-IRISIN-uncoupling protein-1 (PGC-1α-IRISIN-UCP-1) pathway in the beigeization of white adipose tissue. Methods: Four-week-old male C57BL/6 mice were randomly divided into normal (NC) and high-fat diet (HFD) groups. After 10 weeks of HFD feeding, obese mice were randomly divided into obesity control(OC), obesity diet control (OD), obesity exercise (OE), and obesity diet control exercise (ODE) groups. Mice in OE and ODE performed moderate-load treadmill exercises and the diet constituted 70% of the food intake of the OC group for 8 weeks. Results: Long-term HFD inhibits white adipose tissue beigeization by downregulating PGC-1α-IRISIN-UCP-1 in the adipose tissue and skeletal muscles. Eight weeks of exercise and dietary interventions alleviated obesity-induced skeletal muscle and adipose tissue PGC-1α-IRISIN-UCP-1 pathway downregulation promoted white adipose tissue beigeization and reduced body adipose tissue. The effects of the combined intervention were better than those of single interventions. Conclusions: Diet and exercise intervention after obesity and obesity itself may affect the beigeization of WAT by downregulating/upregulating the expression/secretion of skeletal muscle and adipose PGC-1α-IRISIN, thereby influencing the regulation of body weight. The effects of the combined intervention were better than those of single interventions.
... 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). ...
Conference Paper
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Fitokimyasallar, bitkiler tarafından çeşitli kimyasal yollarla üretilen besleyici olmayan kimyasal bileşiklerdir. Sağlık üzerine birçok yararlı etkileri olan fitokimyasallar polifenoller, terpenoidler, organosülfürler, fitosteroller olmak üzere dört başlık altında incelenebilir. Polifenoller kendi içinde 5 ana başlığa daha ayrılır: Basit fenolik asitler, stilbenler, kurkuminoidler, lignanlar ve flavonoidler. Terpenoidlerin arasında karotenoidler (laykopen, lutein ve karoten) ve sesquiterpenler bulunur. Organasülfür bileşikler arasında allil sülfit, allisin ve alliksin bulunur. Bu bileşikler sarımsak, soğan, pırasa gibi sebzelerde bol miktarda bulunmaktadır. Son olarak kolesterol benzeri yapıda olan ve kalp sağlığı ile ilgili önemli etkileri olduğu düşünülen fitostreroller arasında kampestrol, stigmasterol ve sitosterol bulunur. Birçok hastalığın önlenmesi veya tedavisinde etkili olan fitokimyasallar sebzelerde yoğun olarak bulunur. Genel olarak sebzeler pişirilerek tüketilmektedir. Toplumda sebzelerin çiğ olarak tüketilmesinin daha doğru olduğu kanısı olsa da pişirme ile aktif olan biyoaktif bileşikler nedeniyle pişirmenin olumlu yanları da vardır. Pişirmenin sebzeler üzerinde tek bir etkisi yoktur. Bunun sebebi sebze türlerinin farklı olması olduğu gibi pişirme süresi, sıcaklık gibi etkilerden kaynaklanıyor olabilir. Pişirme yöntemlerinden biri olan haşlama yöntemi pişirme yöntemleri arasında beslenme ve diyetetik uzmanları tarafından en çok önerilen yöntemlerden biridir. Son zamanlarda haşlama suyuna geçen vitamin ve mineraller nedeniyle haşlamanın sağlıklı olarak değerlendirilmesi sorgulanmaktadır. Bu nedenle bu çalışmada fitokimyasalları kategorize etmek ve fitokimyasalların yoğun olarak bulunduğu çeşitli sebzelerde haşlama yöntemi ile fitokimyasalların değişimini incelemek amaçlanmıştır.
... 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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Obesity is a global health problem and a major risk factor for several metabolic conditions including dyslipidemia, diabetes, insulin resistance and cardiovascular diseases. Obesity develops from chronic imbalance between energy intake and energy expenditure. Stimulation of cellular energy burning process has the potential to dissipate excess calories in the form of heat via the activation of uncoupling protein-1 (UCP1) in white and brown adipose tissues. Recent studies have shown that activation of transforming growth factor-β (TGF-β) signaling pathway significantly contributes to the development of obesity, and blockade or inhibition is reported to protect from obesity by promoting white adipose browning and increasing mitochondrial biogenesis. Identification of novel compounds that activate beige/brown adipose characteristics to burn surplus calories and reduce excess storage of fat are actively sought in the fight against obesity. In this review, we present recent developments in our understanding of key modulators of TGF-β signaling pathways including follistatin (FST) and myostatin (MST) in regulating adipose browning and brown adipose mass and activity. While MST is a key ligand for TGF-β family, FST can bind and regulate biological activity of several TGF-β superfamily members including activins, bone morphogenic proteins (BMP) and inhibins. Here, we review the literature supporting the critical roles for FST, MST and other proteins in modulating TGF-β signaling to influence beige and brown adipose characteristics. We further review the potential therapeutic utility of FST for the treatment of obesity and related metabolic disorders.
... Previous studies have not found a relationship between gender and irisin levels in obese people (Lopez-Legarrea et al., 2014;Blüher et al., 2014). However, in this study the difference between male and female poults in irisin levels bordered on being significant (P =0.054). ...
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In this study, the effects of different methods of feeding turkeys on the neuropeptide nesfatin-1 and the hormone irisin were evaluated. A total of 90 turkeys were distributed to three treatment groups, namely T1: conventional system, T2: 50% feed and pasture, and T3: pasture. There were 30 birds in each group with three random replications. The birds were fed for 18 weeks. At the end of the study, blood was collected from 10 birds of each group. Plasma nesfatin-1 and irisin levels were measured with an enzyme-linked immunoassay. The nesfatin-1 levels of male turkeys in T1, T2, and T3 were 0.76 ± 0.1 ng/m, 0.41 ± 0.1 ng/ml, and 1.24 ± 0.2 ng/ml, respectively. Nesfatin-1 levels in the female turkeys in T1, T2 and T3 were 0.53 ± 0.07 ng/ml, 1.18 ± 0.3 ng/ml, 1.32 ± 0.1 ng/ml, respectively. The irisin levels in the male turkeys in T1, T2, and T3 were 575.93 ± 42.5 pg/ml, 188.39 ± 1.8 pg/ml, and 607.54 ± 24.1 pg/ml, respectively. Irisin levels of the female turkeys in T1, T2 and T3 were 603.20 ± 42.2 pg/ml, 241.42 ± 18.4 pg/ml, and 399.29 ± 21.5 pg/ml, respectively. Because nesfatin-1 is involved in regulating food intake, food intake by turkeys might differ, depending on the management system. Different management systems might also alter irisin secreation because it can be induced by exercise.
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Incretins are gut hormones that potentiate glucose-stimulated insulin secretion (GSIS) after meals. Glucagon-like peptide-1 (GLP-1) is the most investigated incretin hormone, synthesized mainly by L cells in the lower gut tract. GLP-1 promotes β-cell function and survival and exerts beneficial effects in different organs and tissues. Irisin, a myokine released in response to a high-fat diet and exercise, enhances GSIS. Similar to GLP-1, irisin augments insulin biosynthesis and promotes accrual of β-cell functional mass. In addition, irisin and GLP-1 share comparable pleiotropic effects and activate similar intracellular pathways. The insulinotropic and extra-pancreatic effects of GLP-1 are reduced in type 2 diabetes (T2D) patients but preserved at pharmacological doses. GLP-1 receptor agonists (GLP-1RAs) are therefore among the most widely used antidiabetes drugs, also considered for their cardiovascular benefits and ability to promote weight loss. Irisin levels are lower in T2D patients, and in diabetic and/or obese animal models irisin administration improves glycemic control and promotes weight loss. Interestingly, recent evidence suggests that both GLP-1 and irisin are also synthesized within the pancreatic islets, in α- and β-cells, respectively. This review aims to describe the similarities between GLP-1 and irisin and to propose a new potential axis–involving the gut, muscle, and endocrine pancreas that controls energy homeostasis.
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Type 2 diabetes is now a pandemic and shows no signs of abatement. In this Seminar we review the pathophysiology of this disorder, with particular attention to epidemiology, genetics, epigenetics, and molecular cell biology. Evidence is emerging that a substantial part of diabetes susceptibility is acquired early in life, probably owing to fetal or neonatal programming via epigenetic phenomena. Maternal and early childhood health might, therefore, be crucial to the development of effective prevention strategies. Diabetes develops because of inadequate islet β-cell and adipose-tissue responses to chronic fuel excess, which results in so-called nutrient spillover, insulin resistance, and metabolic stress. The latter damages multiple organs. Insulin resistance, while forcing β cells to work harder, might also have an important defensive role against nutrient-related toxic effects in tissues such as the heart. Reversal of overnutrition, healing of the β cells, and lessening of adipose tissue defects should be treatment priorities.
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Objective: Low-carbohydrate (L-CHO) diets are often used for weight loss but their effects on cognitive function are not well understood. The present study compared the effects of a L-CHO and high-carbohydrate (H-CHO) weight-loss diet on cognitive function adults. Design: PARTICIPANTS were randomized to either a L-CHO (n=22) or H-CHO (n=25) weight-loss diet. Cognitive function was evaluated by four computerized cognitive tasks (Stroop Task, Continuous Performance Task, Word Recall and Wisconsin Card Sorting Task) presented in random order before and at 1, 4, 12 and 24 weeks after the initiation of the L-CHO or H-CHO diet. Participants: Forty-seven adults (25 males) with a mean±s.d. age of 47.4±8.7 years and body mass index of 35.3±3.4 kg m(-2). Results: There were no significant differences in weight loss between groups at any time point. There were significant improvements on color Stroop task accuracy over time in both diet groups (P<0.05), but there were no differences in performance between groups on this or any other cognitive task at any time period. Conclusion: These findings suggest that weight loss has neither a positive nor a negative effect on cognitive function and that L-CHO and H-CHO weight-loss diets have similar effects on cognitive performance.
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Differences in body fat distribution contribute to the metabolic abnormalities associated with overweight and obesity; however, such differences have not been adequately explored during pregnancy. Our aim was to compare longitudinal trends in maternal abdominal adipose tissue deposition during pregnancy in overweight/obese compared with normal weight women. Pregnant women, classified as normal weight (body mass index (BMI) <25 kg m(-2); N=61) or overweight/obese (BMI 25 kg m(-2); N=57), were enrolled in a prospective cohort study starting in the first trimester. Maternal subcutaneous (smin) and preperitoneal (pmax) fat were measured by ultrasound at five time points starting between 6 and 10 weeks gestation. The abdominal fat index (AFI), an established marker of visceral adipose tissue, was calculated as the ratio of pmax to smin. The trajectories of smin, pmax, cumulative fat index (smin plus pmax) and the AFI across pregnancy were analyzed using mixed linear models. The rate of maternal weight gain during pregnancy was significantly lower for overweight/obese women compared with their non-overweight counterparts (P<0.05). Accordingly, the rate of change of pmax and smin differed significantly in normal weight compared with overweight/obese women (P=0.0003 and 0.01, respectively). The cumulative fat index did not change across gestation in normal weight women, whereas it decreased for overweight/obese women (P=0.0005). The log AFI increased across pregnancy in both strata, but significantly more rapidly for normal weight compared with overweight/obese women (P=0.06). Adipose tissue is preferentially deposited in the more metabolically active visceral compartment as pregnancy progresses. However, this process differs in normal weight compared with overweight/obese women and may contribute to metabolic differences between these groups. Our study is a step toward a more refined description of obesity and its consequences during pregnancy.
Objectives The aim of this study was to compare the effect of two energy-restricted, differing with regard to protein content, on the inflammation state of obese individuals with features of metabolic syndrome. Methods Ninety-six participants completed an 8-wk randomized intervention trial that compared the RESMENA diet (−30% energy, with 30% energy from protein) with a control diet (−30% energy, with 15% energy from protein) that was based on American Heart Association criteria. Results The mean body weight losses were 7.09 ± 0.82 kg and 6.73 ± 0.71 kg, respectively, with no differences seen between the groups. The endpoint inflammation score—which was based on high-sensitivity C-reactive protein, interleukin-6, tumor necrosis factor-α, and plasminogen activator inhibitor-1 levels—was significantly lower (P = 0.012) in the low-protein group (6.81 ± 2.32 versus 7.94 ± 1.94). The linear regression analyses revealed that total protein intake was positively associated with inflammation (P = 0.007) as well as with animal protein (P = 0.025) and meat protein (P = 0.015), but neither vegetable- nor fish-derived proteins were found to influence inflammatory status. Conclusions Our results suggest that the type of protein consumed (more than the total protein consumed) within an energy-restricted diet influences the inflammation status associated with obesity-related comorbidities.
Many important associations have been found between the newly discovered myokine irisin and measures of metabolic disease. However, not much is known regarding the role of irisin in human disease. Two recent reports now identify novel metabolic associations for this molecule in humans.
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.
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.
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.