AN UPDATE ON IRISIN TRIGGERS AND EFFECT OF EXERCISE TRAINING
ON SEDENTARY WOMEN SERUM IRISIN LEVEL
By
MAHNOOR
F18-BSZOO-1062
Session: 2018-2022
Thesis submitted in partial fulfilment of
the requirements for the degree of
BACHELORS
IN
ZOOLOGY
DEPARTMENT OF ZOOLOGY,
UNIVERSITY OF OKARA (PAKISTAN)
1
ABSTRACT
Irisin is a myokine secreted into the bloodstream by the proteolytic cleavage of precursor
fibronectin type III domain containing 5 (FNDC5). Irisin after its release activates mitochondrial
uncoupling protein 1(UCP1) and transforms white adipose tissue (WAT) into brown adipose tissue
(BAT). Irisin is expressed in various brain and muscle tissues. The serum irisin levels are regulated
by a number of factors such as exercise, temperature, diet, obesity, insulin resistance and various
pathological states. It has been suggested that irisin secretion is triggered by muscle contraction.
In this review, we have discussed the chief triggers of irisin secretion and effect of exercise on the
circulating serum irisin level in sedentary women. In conclusion, irisin level significantly increased
after physical activity of sedentary women.
KEYWORDS
FNDC5, Exercise, Obesity, Insulin Resistance.
INTRODUCTION
Skeletal muscle is not just for motility, but also perform endocrine functions by producing myokine
(Pedersen & Febbraio, 2012). One of the most recently discovered myokine is irisin firstly
observed in animals then in humans by Bostrom in 2012 in Harvard University (BostrÖm, Wu,
Jedrychowski, & Korde, 2012). Irisin, primarily discussed as a myokine of skeletal and cardiac
muscle triggered by exercise and exposure to low temperatures, endorsing an adaptive response of
browning and thermogenesis (Flori, Testai, & Calderone, 2021).
About 60 % of its release from skeletal muscles. However, some studies have shown that it can
also be released from liver, pancreas, testis, liver and stomach (Korta, Pocheć, & Mazur-Biały,
2019). As we know that irisin is a myokine thus, it gets activated and regulated by muscular activity
and stimulation. Our day-to-day lifestyle has a huge impact on our body. Changes in lifestyle, diet
and physical activities effect our body and different hormones stimulated actions and functions
significantly. Exercise or increase in physical activity stimulates irisin secretion. Its level may
fluctuate and go up or down in people living with sedentary or non- sedentary lifestyle depending
upon their regular physical activities.
2
SYNTHESIS OF IRISIN
The level of Irisin and its release and biosynthesis is effected by exercise and PGC1-α (Waseem
et al., 2021). As mentioned, exercise effects the level and release of Irisin. Irisin was found to be
released only after intense exercise or through thermogenesis via the release of PGC1- α and
proteolytic breakdown of FNDC-5. Thus, assuming that its level may go up or down in people
living with sedentary or non- sedentary lifestyle depending upon their daily activities. PGC1- α is
a transcriptional coactivator that is involved in energy metabolism. In skeletal muscle, PGC1- α is
produced by exercise by initiating mitochondrial biogenesis, angiogenesis and fiber – type
switching (Handschin & Spiegelman, 2008). PGC1- α also plays an important role in inciting the
release of skeletal muscle factor that can change the working of other tissues.
The synthesis of Irisin started when a person performs prolonged intensive exercises. In case of
prolonged exercises the PGC1- α expresses itself in different organs like heart and skeletal muscle
which causes insulin sensitivity and signaling (Norheim et al., 2014). Due to prolonged exercises,
the level of Ca+2 in the blood that in turn enhance the secretion of various gene products from the
muscle including FNDC-5 through PGC1- α. FNDC-5 gene then encode the protein to release
Irisin in blood (Pontus Boström, Jun Wu, Mark P Jedrychowski, et al., 2012). Akimoto et al.
showed that prolonged intense exercises and increases muscular activity with the surge in Ca+2
triggers the start of P38 MAPK pathway.
Figure 1 IRISIN synthesis; p38pathway
3
In C2C12 cells, the start of P38 MAPK instigates the start of PGC1- α pathway whose release is
later blocked by P38 inhibitors. Studies suggest that activation of P38 pathway in mice result in
appearance of PGC1- α protein (Akimoto et al., 2005). Some studies have also shown that control
in release of PGC1- α is due to a cellular transcription factor cAMP response element Binding
protein (CREB) (Handschin, Rhee, Lin, Tarr, & Spiegelman, 2003) . Safarpor et al. in 2020 showed
that serum level of Sirtuin (Sirt 1) and Irisin increases due to the intake of Vitamin D supplement
which shows the relation between Irisin and Sirt 1. The involvement of Sirt 1 cause release of
PGC1- α and FNDC-5 (Safarpour et al., 2020).
Hence, the P38 pathway cause the release of PGC1- α gene that leads to FNDC5 upregulation and
its proteolytic breakdown produces irisin. The triggers of P38 pathway; Ca+2 upsurge that was due
to prolonged and intense physical activity caused alternation in skeletal muscle. The involvement
of CREB and Sirt 1 pathway causes regulation and association of FNDC-5 and PGC1-α in irisin
release.
FNDC-5 and Irisin Structure
Irisin is an exercise-induced myokine. It is a peptide consist of 112 amino acids (Hecksteden et
al., 2013). Irisin emerges from type I membrane protein breakdown encoded by fibronectin type
III domain containing 5 (FNDC5) genes(Pontus Boström, Jun Wu, Mark P Jedrychowski, et al.,
2012). FNDC-5 protein has mass that ranges from 20 to 32 kDa. This mass of FNDC-5 protein
rely on the oligosaccharide structure and number which combine with FNDC-5. FNDC5 is a 29amino acid signaling peptide, a 94-amino acid domain and has two segments a C- terminal and N
– terminal. The C- terminal side present in the cytoplasm which is lytic site of peptide before it is
being secreted into circulation as irisin while the N- terminal in extracellular region breakdown
that produce Irisin (Pontus Boström, Jun Wu, Mark P Jedrychowski, et al., 2012) (Schumacher,
Chinnam, Ohashi, Shah, & Erickson, 2013) (H. K. Kim et al., 2017b). Irisin is a glycosylated
protein hormone, a fragment of a cell membrane protein called fibronectin type III domaincontaining protein 5 (FNDC5). The removal of glycosyl radical in irisin decreases its molecular
weight. The structure of Irisin under X- ray crystallography shows that Irisin occurs in form of
homodimers where β- sheet is created between the units (Pontus Boström, Jun Wu, Mark P
Jedrychowski, et al., 2012) (Roca-Rivada et al., 2013).
4
Figure 2 FNDC5 proteolytic breakdown into irisin
FNDC-5 is an N- glycosylated protein. De- glycosylation can affect the stability and location of
FNDC-5. In fact, the de-glycosylated FNDC-5 is somehow more subtle towards the action protein
synthesis, inhibitors compared towards the glycosylated molecule. De- N- glycosylation can also
cause the half-life of FNDC-5. (Nie & Liu, 2017).
Irisin has expression in other mammals as well, and have been found to have almost functions and
structure; as in between mice and humans, it is exactly same (Aydin, 2014).
Receptors of Irisin
Gene expression of FNDC5 mRNA seems to be extensively expressed in tissues of brain and
muscle (H. K. Kim et al., 2017a; B. M. Varela-Rodríguez et al., 2016). The expression of FNDC5
been found to be influenced by important body peptide hormones such as insulin, glucagon and
leptin and might be regulating glucose homeostasis (B. M. Varela-Rodríguez et al., 2016).
Kim proposed in a recent study that the αV family of integrin receptors are likely Irisin receptors
in fats and bone cell (H. Kim et al., 2018). Integrins are expressed as transmembrane receptors that
binds with cell matrix interactions and intercellular interactions and soluble ligands (Takada, Ye,
& Simon, 2007) They play an important role in union, accumulation and movement of cells
(Rabiee et al., 2020). Non Covalent interactions are present between 18α- subunits and 8 βsubunits that can make 24 integrin heterodimers (Takada et al., 2007). Kim suggested that the
5
limiting of Irisin to a few integrins present in fat cells and bone cells include α1β1 and with most
elevated to high affinity to αvβ5 integrins. The treatment of bone cells with Irisin efficiency
expanded the phosphorylation level of central bond kinase FAK (Major intracellular signal
molecules that play an important role for integrin signaling). The utilization of RGD peptide which
ties to αvβ5 and goes about as response that is activated by Irisin The writers proposed that
heterodimers having place with αV integrin family are likely the primary receptors for Irisin in
every tissue (H. Kim et al., 2018). All the above data reported that however there has been no
receptor of Irisin has recognized but the action αV/β5 integrin takes place in adipose and bone
tissues (Pignataro et al., 2021).
Blood Level of Irisin
Bostrom et al. 2012 first time revealed the level of irisin in control mice which is about 40nm
(Pontus Boström, Jun Wu, Mark P Jedrychowski, et al., 2012). Jedrychowski and his colleagues
suggested that the level of irisin is 3- 5 ng/ ml. But some studies also reported that the level of
Irisin in rodents and humans varies considerably (Jedrychowski et al., 2015). The level of Irisin
varies depends upon the lifestyle of individuals. Kits like EIA and RIA are used to measure
biological fluid levels. These kits suggested the level of Irisin varies from 50pg/ml to more than
10 mg/ ml (Jedrychowski et al., 2015).
Different western blots have been used to study the estimated value of Irisin by reacting it with
other protein serum (Bain et al., 2007). So, the normal level of Irisin have not been identified yet.
Irisin can be found in both glycosylated and non- glycosylated forms which then leads to confusion
of its level in blood. Different mass spectrometry techniques that have been developed that helps
to check the level of Irisin (Jedrychowski et al., 2015). For the distribution of Irisin Kim et al.
suggested the short half-life of recombinant Irisin injected in mice (H. Kim et al., 2018). If this
short half-life is also valid for the local Irisin. Mice and other species this may be an important
factor accounting for a change in detection of Irisin in blood (Albrecht et al., 2020). Bostrom
observed after 10 weeks of training the level of adipomyokine increased by twice in blood of
healthy people and hence the level of Irisin increases (Pontus Boström, Jun Wu, Mark P
Jedrychowski, et al., 2012).
However, still the effect of physical exercise on the concentration of Irisin in blood has not been
completely identified yet and thus there is no absolute result. In some cases, it has been observed
6
that the people who lives a non – sedentary lifestyle has lower level of Irisin in blood (Qiu et al.,
2015). In some cases, the level of Irisin has found to be in normal concentration to be 3.6 ng/ml
and in people having a sedentary lifestyle to be 4.3ng/ml (Jedrychowski et al., 2015). Patients of
renal Failure has Irisin in lower concentration.
The concentration of irisin also depends on the gender. It has been observed that there is lower
level of Irisin in obese men then in women. It means women usually shows higher level of Irisin
which then cause involvement of estradiol a hormone which then leads to higher muscle mass and
increased concentration of Irisin in women (Al‐Daghri et al., 2014; Fukushima et al., 2016; Yan
et al., 2014).
Factors triggering Irisin secretion
In some studies, Irisin has considered to be increased after exercise. However, there is
disagreement in results and complex link between exercise and level of Irisin. Irisin is primarily
discussed as a myokine of skeletal and cardiac muscle triggered by exercise and exposure to cold,
work by endorsing browning mechanism and thermogenic response in fat tissues. Irisin has a link
with usage of energy. It is a pleiotropic hormone interceding the beneficial effects of exercise and
enhanced physical activity including energy expenditure or fat oxidation (Pontus Boström, Jun
Wu, Mark P Jedrychowski, et al., 2012). Irisin is released only after heavy exercise or through
thermogenesis by the release of PGC1- α and proteolytic breakdown of FNDC-5. Conversely,
recent reports infer a complex relationship with exercise, exposure to cold and irisin in animal as
well as human studies conflicting with the earlier literature.
Animal study:
In 2012 Bostrom found a depleted UCP1 expression when injected the mice understudy with antiFNDC5 antibodies before subjected to exercise, this suggested that irisin releasing pathway is
important factor in the effect of exercise that activates the browning of WAT (Pontus Boström,
Jun Wu, Mark P. Jedrychowski, et al., 2012). Exercise stimulates a significant enhancement in the
expression of PGC-1α, mRNA of gene FNDC5, and irisin in blood (Pontus Boström, Jun Wu,
Mark P. Jedrychowski, et al., 2012; Huh et al., 2012a). Endurance exercise has been found to be
prominent factor in triggering UCP1 and FNDC5 expression in mice under study (Reisi, Ghaedi,
Rajabi, & Marandi, 2016; Wrann et al., 2013). While treadmill run showed immediate but shortlived surge in irisin levels (Brenmoehl et al., 2014). Tavassoli in 2019, used mice induced with
7
type 2 diabetes millitus in resistance exercise program that resulted in dramatic drop of irisin level
after T2DM induction and upraise after exercise (Tavassoli, Heidarianpour, & Hedayati, 2022).
Human study:
Some factors that can control the level of Irisin include obesity, drugs, lipid profile, pathological
conditions that include renal failure and other hormonal conditions (Novelle, Contreras, RomeroPicó, López, & Diéguez, 2013). Here some factors are discussed.
Exercise and Low Temperature:
Researches have been up to find the answers since a decade now, the reports from first half of
decade agreed upon idea that the exercise and increased physical activity triggers the irisin
expression however, reports from past 5 years are at variance, evident toward decrease in
concentration of irisin in different diseases like obesity and diabetic conditions (José María
Moreno-Navarrete et al., 2013; Yan et al., 2014; Z. Yang, Chen, Chen, & Zhao, 2015). Studies
reveal resistance and higher irisin levels in observed obese subjects (F. De Meneck, Victorino de
Souza, Oliveira, & do Franco, 2018; Sahin-Efe et al., 2018a). All the experimental data exhibit
that overall upregulation is just an act of maintaining a certain concentration of irisin in blood after
exercise or some physical activities under some pathological states.
Lee et al. in 2014, confirmed the positive correlation of exercise and cold with irisin secretion.
However, the difference in work done and energy consumed while doing maximal exercise and
change during cold was very clear that exercise made a prominent mark in triggering irisin levels.
The levels of irisin doesn’t confine with work down which indicates that exercise and exposure to
cold are independent factors (Lee et al., 2014). A systematic review, from 2017 proposed that
exercise is not the only trigger in exaggeration of the circulation of irisin and UCP1 production,
but it might be combined reaction to colder temperatures and exercises (Flouris et al., 2017). Coker
et al. in same year, measured the serum level of irisin in healthy subjects. He found that low
temperature and intense exercise encouraged a significant rise in irisin, making it more evident
that a positive correlation exists (COKER et al., 2017). Ӧzbay et al. in 2020 witnessed a slight rise
in serum irisin value that was brought about by aerobic exercise. However, an 18-week training
program depicted no noticeable change in irisin levels, yet dropped considerably when aerobic
exercises were performed at regular temperature (25-27 ⁰C), suggests temperature regulation sure
does effect irisin release (Ozbay et al., 2020).
8
Table: Effect on irisin production after exercise and exposure to low temperatures.
Research/ Year
(Pontus
Stimulus
Aerobic training (4–5
Boström, Jun
sessions of half hour/
Wu, Mark P
week)
Subjects
Results
Healthy subjects
↑ irisin
Adult women (no
↑ irisin in adults
exercise), obese (no
↓ irisin and
exercise) and healthy
FNDC5 in obese
Jedrychowski,
et al., 2012)
(Huh et al.,
2-months training
2012a)
young athletes
(Lee et al.,
2014)
An hour-long
Healthy human
endurance training,
↑ irisin and
FNDC5
cold exposure
Acute exercise training
Healthy adults
↑ irisin
(Nygaard et al.,
1-hour intense
Healthy subjects
↑ irisin, PGC-1α,
2015)
endurance/ strength
(Daskalopoulou
et al., 2014)
FNDC5 (brief)
training
(Löffler et al.,
Half hour intensive
Healthy adults/obese
↑ irisin after
2015)
exercise, 6-week-
children
stimulus (brief)
Running
Human
↑ irisin
(Palacios-
8-month aerobic
Norma/obese children
no change in
González et al.,
training
chronic in-house
exercise
(Hew-Butler et
al., 2015)
concentration
2015)
9
(Blizzard
45-min aerobic and 6-
LeBlanc et al.,
week endurance
2017)
exercise
(COKER et al.,
2017)
Cold exposure or
Obese adults
↑ irisin
Healthy subjects
↑ irisin
↑ irisin
intense aerobic
exercise
(Morelli et al.,
Vigorous-intensity
Mediterranean-diet fed
2020)
physical activity
teenagers
(Ozbay et al.,
Outdoor and Indoor 40- Healthy subjects
2020)
↓ irisin in indoor
min running for 18
no change in
weeks
outdoor
Exercise
The control of FNDC5 expression and the change in level of Irisin by exercise is controversial
(Pontus Boström, Jun Wu, Mark P Jedrychowski, et al., 2012). Huh and his colleagues observed
that there is a relation between FNDC-5 expression and level of Irisin (Huh et al., 2012b).
Depending upon the difference in intensity and time of exercise session can cause the difference
in the result. Continuous strength training can help to increase the level of Irisin in aged mice and
it also helps to have a better strength of muscle in non- sedentary old animals (H.-j. Kim, So, Choi,
Kang, & Song, 2015). It has been mentioned in various papers that exercise and diet in unite have
a huge effect in prolonged exercises can affect the energy usage and browning of fat by changing
UCP1, PGC1- α, FNDC-5 expressions in all skeletal muscle. These types of changes have been
observed in all types of feeding animals (Morton et al., 2016). Myokine are released after muscle
contraction, so there might have a link between exercise and protection against diseases and their
relationship with physical activity of an organism (Pardo et al., 2014). Steward has studied in
humans the relationship between FNDC-5 and PGC1- α genes with physical exercises measured
through gas exchange. According to him there is a positive relationship between PGC1- α and
FNDC-5 genes and the aerobic capacity which is same in articles published by Bostrom (Lecker
et al., 2012). Kim suggested a positive relation between Irisin and improvement in strength of legs
in aged individuals after a few weeks of exercise program. The writers have written that irisin is a
hormone that helps to increase the muscular function in aged individuals (H.-j. Kim et al.,
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2015).When the level of ATP in muscle decreases the concentration of irisin increases (Huh et al.,
2012a). Some studies have also shown that exercise is stimulus that helps to provoke the release
of Irisin in body (Fatouros & Medicine, 2018; Fox et al., 2018). The strength of exercise can be an
important factor that effects the release or the removal of Irisin. Because the strength of exercise
is low then the concentration of Irisin also decreases as compared to the level right after exercise
in contrast to high intensity at the same time (Nigg et al., 2017). Exercises show powerful stimulus
for the secretion of Irisin if the intensity is appropriate and its level decreases right after 1 hour
(Huh et al., 2015). But some papers have shown that the level of Irisin increases from 30 min. to
1 hour after exercise (Tsuchiya et al., 2014).
It recommends that time course changes of irisin fixation in light of intense activity are
complicated. Notwithstanding the factors like activity power, term and subjects' health status, a
more upgraded practice program that incorporates a detail time course is expected to investigate
the reaction of irisin to intense practice from here on out. It is recommended that irisin fixation
with regard to intense physical activities are complicated. Anyhow the factors like activity power,
subject’s wellness level, and the kind of practice program must be considered while investigating
the irisin reaction to exercise.
A study conducted on healthy human subjects in 2014, hypothesized that muscular energy
requirements upregulated irisin levels in body. The study showed intense physical activity, leads
to significant increase in irisin levels that may be trigger by high muscle tension and low ATP
production (Daskalopoulou et al., 2014). In 2015, a study showed a surge in serum irisin levels
was reported after short but intense training in young adults. However, an exercise training
program administered on obese children showed no major change in irisin levels (Löffler et al.,
2015). On another side a significant escalation in irisin and leptin circulating concentration was
reported in obese youth after exercise (Palacios-González et al., 2015). Hew-Butler et al., showed,
irisin downregulation after 10 weeks aerobic training (Hew-Butler et al., 2015). A later conflicting
human study shown a raise in irisin levels in obese adults after submaximal exercise, whereas no
changes were reported after 6-week long endurance training (Blizzard LeBlanc et al., 2017).
Higher irisin levels in active participants than in sedentary ones and negative correlation with
metabolic parameters like cholesterol, LDL and triglycerides during intense physical activity was
reported in adults in a 2020 study (Morelli et al., 2020).
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Obesity
Obesity is epidemic of 21st century and a major reason of death in different parts of world. Obesity
is the reason to spread various diseases including diabetes mellitus and cardiovascular disease.
Irisin is a myokine that leads to increased energy expenditure by stimulating the 'browning' of
white adipose tissue. Many studies have shown the relation between obesity and regulation of
Irisin. Overweight individuals have shown alteration in level of Irisin and FNDC-5 expression.
Some studies have shown a down-regulation of FNDC-5 expression in skeletal muscle and adipose
tissues caused by obesity (Lu et al., 2016; Morton et al., 2016; Rocha-Rodrigues et al., 2016; X.
Yang et al., 2016; Zaigang Yang, Chen, Chen, Zhao, & pathology, 2015).
Irisin is a myokine that is secreted from adipose tissues as well beside directly from skeletal
muscles tissues (Roca-Rivada et al., 2013). That’s why called, adipokine and thus, it also
modulates the advantageous effects of exercise (Grygiel-Górniak & Puszczewicz, 2017). In
humans, the circulation of FNDC-5/Irisin is hundred times less in white adipose tissues as
compared to muscle (Perakakis et al., 2017). Many studies have shown the link between the level
of irisin and obesity in humans. It has been studied by many researchers that there is a positive
link between the level of Irisin in blood, adiposity and BMI (Crujeiras et al., 2014; Grygiel-Górniak
& Puszczewicz, 2017; Hee Park et al., 2013; Kleerebezem, 2004; Liu et al., 2013).
While on the other hand some studies have also shown a negative relation between Irisin , BMI
and the no fat tissues (Grygiel-Górniak & Puszczewicz, 2017). The concentration of Irisin when
of irisin when observe in obese people. In the beginning it was observed that obese people has
higher level of Irisin (Franciele De Meneck, de Souza, Oliveira, do Franco, & Diseases, 2018;
Sahin-Efe et al., 2018b). According to Pardo 1kg increase in fat mass can cause the Irisin level to
double (Pardo et al., 2014). While some studies have also shown that weight loss in obese
individuals cause decrease in level of Irisin (Crujeiras et al., 2014; Huerta et al., 2015). In
compliance to above discussed point, Yan et al. study on Chinese young obese group of people
implicated upon a negative relation between the muscular mass and irisin concentration. The
concentration of irisin decreases as waist circumference, hip circumference increase (D. Espes, J.
Lau, & P. O. Carlsson, 2015).
Some studies have also shown no relation between obesity and FNDC-5/Irisin level (Pekkala et
al., 2013; Peterson, Mart, & Bond, 2014; Roberts et al., 2013). Irisin concentration compared in
12
normal weight, overweight, and obese healthy individuals in a study in 2014, showed no major
differences (Sanchis-Gomar et al., 2014).
In a research, higher concentration of circulating irisin in obese people in comparison with normal
weight and anorexia people was reported, hints toward positive association between the percentage
of fat mass and irisin concentration and a negative correlation with fat free mass. In this study, it
was implied that condition of obesity in humans may be affected by different types of adipose
tissues depending upon amount of irisin being produced by these tissues; Pardo also, evidenced
towards possible irisin resistivity (Pardo et al., 2014).
There’s a positive relation between Irisin and the obesity been observed that shows obesity
increases the level of Irisin. The positive affiliation was made on the basis of Irisin level drop
following weight reduction which happens because of loss of muscle mass. But as suggested earlier
muscles have higher concentration of irisin, thus losing muscle mass leads to drop in irisin
concentration.
Furthermore, it has been recommended that higher level Irisin could be a compensatory instrument
for unusual digestion and insulin sensitivity in obese people (Huh et al., 2012a). Recently, a metaanalysis study stated that the irisin level is higher in obese than normal weight individuals (Jia et
al., 2019). Roca Rivada and his colleagues have shown that the precursor of Irisin, PGC1-α,
expressed higher level of Irisin in adipose tissues than in muscles after exercise in relation with
the release of Irisin. Like other adipokines, irisin discharge from subcutaneous fat tissues is
affected by circulating level of Irisin (Roca-Rivada et al., 2013).
This came in occurrence with Moreno Navarrate who revealed that better expression of FNDC-5
in fat tissue was found and further established that the capacity and limit of fat tissues are
accomplished by a positive feedback mechanism by surging the level of Irisin which drove them
to hypothesize that Irisin can additionally be emitted from fat tissues (J. M. Moreno-Navarrete et
al., 2013).
Insulin Resistance and Diet
Irisin is a type of hormone that stimulate beneficial changes in adipose tissue; thus, an increases in
irisin improves insulin resistance induced by a diet (Pontus Boström, Jun Wu, Mark P
Jedrychowski, et al., 2012). In a study, obesity and Insulin resistance data showed that high caloric
diet is not linked with higher level of Irisin.
13
In all the non – diabetic individuals, it has been found that there is a positive relation between the
level of Irisin and insulin resistance (Huerta et al., 2015; Li et al., 2015; Moreno et al., 2015). Some
studies reported that increase in level of Irisin may be because of increase glucose level. Moreover,
the increase in level of Irisin can be found to be a sign for insulin resistance. Some papers on the
other hand suggested that there is no link between insulin and irisin on (Fasting Plasma Glucose)
FPG test (Chang et al., 2014; Hirsch, Gross, Pollak, Eldar-Geva, & Gross-Tsur, 2015; Huh et al.,
2012b). A negative relation between glucose and irisin metabolism has been found. Decreasing
irisin concentration
increased
the possibility of metabolic syndrome and hyperglycemia,
considering it to be protective against insulin resistance as it does not show positive associations
between fasting insulin and glycosylated hemoglobin (D. Espes et al., 2015).
All the people with Diabetes Mellitus Type -1 have higher level of Irisin (Ates et al., 2017; D.
Espes, J. Lau, & P.-O. J. D. m. Carlsson, 2015) that cause high inflammatory markers leads to
shattering of insulin producing cells. The reanalyzed studies about Irisin issued in 2015 that
focused on the relationship between Irisin and insulin resistance. The study revealed a positive
relationship between increase inflammatory markers and Diet enriched in Carbohydrates increases
the level of Irisin. While healthy diet shows decrease in level of Irisin which leads to show a
positive relationship between Irisin and insulin resistance (Qiu et al., 2016). Qiu and his colleagues
(Qiu et al., 2016) showed on animals that Diet enriched with fat caused increase in FNDC-5 and
Irisin (Bárbara María Varela-Rodríguez et al., 2016).
EFFECT OF EXERCISE ON SEDENTARY WOMEN
The conversion of white fat into brown fat is contemplated as a solution to overcome many
unwanted problems in human due to obesity. Irisin create heat, energy expenditure, and prevent
obesity by transforming WAT to BAT and activating UCP1(Segsworth (2015)).The aim is to
compare the effect of exercise of various intensities on secretion of serum irisin in sedentary and
non-sedentary women.
HIIT and Control Group of Sedentary Obese Women
A control group of 20 sedentary young obese women of age ranging from 20-30 years and BMI
22-30kg/m2 is subjected to training of 8 weeks. The 10 subjects in control group and rest of the 10
in HIIT group. The session was conducted 3 times per week. Blood samples of subjects observed
14
before after each training session and after 48 hours at the end of study. The serum amount of
irisin, FGF21 and lipid profile were measured in subjects. The level of significance was P≤ 0.05.
High Intensity Interval Training Program
Subjects exercised on treadmill for 8 weeks, 3 times per week. Each training session was of 10
minutes warmup exercise and 4 minutes of repeating bouts with 90% THR. Active recovery
between bouts with 50% THR and 5 minutes cooldown at the end.(Tofighi, Alizadeh, & Tolouei
Azar, 2017)
Table 1: HIIT program (3 sessions per week)
Weeks
Target
Heart
No. of Bouts Duration of Duration of Active
Rate (min)
bouts (min)
(THR)
recovery
recovery
between
intensity
bouts (min)
1st week
90
3
4
2
50-60
2nd week
90
4
4
2
50-60
3rd week
90
5
4
2
50-60
4th week
90
6
4
2
50-60
5th week
90
7
4
2
50-60
6th week
90
8
4
2
50-60
7th week
90
6
4
2
50-60
8th week
90
5
4
2
50-60
HIIT EFFECT ON SEDENTARY OBESE WOMEN
The results of dependent t tests and independent t tests before and after HIIT revealed notable
increase in serum irisin levels and FGF21 levels. Dependent t tests show 7.87% increase in serum
irisin (p=0.001) levels and 6.11% increase in FGF21 levels in sedentary obese women compared
to control group. Independent t tests show significant contrast in irisin and FGF21 levels. Although
there is no notable variation in BMI, HDL-C, LDL-C, VO2 max, cholesterol and LDL/ HDL.
Table 2: Results of Independent and Dependent t-tests in determining the difference between
research variable
15
Variables
Groups
Before-test
After-test
Inter-
Intra
Group
Group
Change
Change
t
p
t
p
-5.95
*0.000
-5.16
*0.000
2.20
*0.041
1.39
*0.128
Irisin
Control
162.03±2.5
162.29±4.4 -0.15
0.87
(ng/ml)
Exercise 162.73±4.5
175.55±7.2 -4.69
#0.001
FGF21 (pg/ml)
Control
249.73±2.7
249.90±3.3 -0.14
0.89
Exercise 250.85±4.4
265.93±6.6 -6.23
#0.000
Control
0.92±0.5
0.91±0.1
0.84
0.43
Exercise 0.91±0.3
0.87±0.2
4.26
#0.0002
Total
Control
169.46±5.3
168.64±4.3 1.16
0.29
Cholesterol
Exercise 170.94±3.3
165.76±4.9 2.83
#0.020
WHR (cm)
(mg/dl)
Case 2: High and Low Intensity RT Group of Sedentary Young Women
A study on sedentary young women showed effect of exercise on irisin level. This study selected
21 sedentary young subjects having BM1 22-25 Kgm2 and age in range of 20-30 years. The
sedentary young subjects were split up into 2 groups and blood samples were taken before and
after each training session that was of 8 weeks. Low and high intensity resistance exercise sessions
were conducted on both groups. The significance degree was P < 0.05.
Acute and Chronic Effect of RT on Sedentary Young Women
The results showed no remarkable change in irisin levels and BMI in both low and high intensity
training groups (P < 0.05). Moreover, irisin level was decreased in subjects after high intensity
training session.(Moienneia & Hosseini, 2016)
Case 3: Exercise and Control Group of Sedentary Diabetic Obese Women
A control and exercise group of diabetic sedentary women subjected to training program in order
to monitor any significant change in irisin levels. Insulin sensitivity, glucose tolerance and
maximal aerobic capacity were measured before and after training session. Samples of skeletal
muscles and subcutaneous adipose tissues were taken in fasting stage and during euglycemic
hyperinsulinemia before and after exercise.
16
Effect of Exercise on Sedentary Diabetic Obese Women
Training session tended to increase the muscle FNDC5 RNA in prediabetic obese subjects but not
in subjects having T2D. FNDC5 and irisin were reduced by 40% and 50% in T2D subjects. Neither
hyperinsulinemia nor exercise affected FNDC5 or Irisin levels. A positive association of irisin
with body metabolism, strength and body mass and negative association with fasting glycemia has
been observed. Exercise didn’t effect serum irisin levels (Timea Kurdiova1, Miroslav Srbecky4,
Christian Wolfrum7, & Jozef Ukropec1 and Barbara Ukropcova1, 2014).
Results
Irisin has a link with energy expenditure, physical activity and certain metabolic factor that may
trigger its circulating concentration. Physical activity triggers the myokine surge. In sedentary
women the concentration of circulating irisin significantly increased after exercise. Metabolic
factors like temperature, obesity, insulin resistance and exercise found to have complex relation
with irisin levels in body. This review of different research data exhibit that overall upregulation
of irisin is just an act of maintaining a certain concentration of myokine in blood only when
triggered by factors such as exercise, temperature or physical activities under some pathological
states.
17
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