one of the most important issues of the health system in the worldwide is obesity , which is presented as one of the top 10 global health problems by the world health organization . nowadays ,
some believe that it is the most perilous disease in the world . in recent years , with increasing prevalence of obesity , an intense interest in clarifying the mechanisms underlying the formation of adipose tissue has been formed . caloric excess , inactivity , and inherited factors are the main causes of changes in adipose tissue , which leads to alterations in its normal function as a lipid buffer , energy store , and a dynamic endocrine organ that is critical for normal metabolic homeostasis .
peroxisome proliferator - activated receptor  gene ( pparg ) is a candidate gene with a direct link to adiposity .
ppar  is a transcription factor , which is abundantly expressed in adipose tissue and has a key role in adipocyte differentiation .
these receptors form heterodimers with the retinoid x receptor ( rxr ) , bind to ppar response elements ( ppres ) in the regulatory region of target genes , and modulate their transcription .
there are a lot of evidence shows that ppar  is a prominent regulator in the formation of fat cells and their ability to function normally in the adults .
ppar  is induced during adipocyte differentiation and forced expression of ppar  in non - adipogenic cells effectively changes them into mature adipocytes .
there is a vast range of naturally compounds seeming to act as ligands for ppars .
it seems that long - chain polyunsaturated fatty acids ( lc - pufas ) are probable candidates as compounds , which regulate ppar  expression .
also , a range of eicosanoids have been shown to be ppar ligands , which often have more coherence than their parent molecules .
some from animal studies showed that n-3 lcpufa supplementation can reduce weight gain and diminish body fat , in particular visceral fat , which is related to changes in gene expression .
some ex vivo studies showed that activation of ppar  in adipose tissue is a possible cause of apoptosis of large fat cells in visceral and/or sc fat depots from rodents .
some studies showed that treatment of zucker ( fa / fa ) rats with thiazolidinedione ( a ppar agonist ) , increased the number of small adipocytes and decreased the number of large adipocytes .
results of these studies imply that ppar  gene expression partially could be controlled , by nutritional regulation .
however , the direct effect of various nutrients on ppar  gene expression is ambiguous .
recent evidence demonstrated interactions between ppar and thyroid hormone nuclear receptors ( trs ) that regulate some genes involved in lipid oxidation and thermogenesis .
the aim of the present study was to verify the effects of n-3lc pufa supplementation on plasma levels of ppar  and thyroid hormones in obesity .
this was a randomized , double - blind , placebo - controlled study in adults with obesity .
sixty six persons were recruited from a specialty and subspecialty clinic of tabriz university of medical science , tabriz , iran , by local advertisements .
the study was carried out from april to november 2011 . by considering 0.05% significant level and 95% power , from other studies ,
the maximum sample size was calculated 25 in each groups , based on t4 ( sd=1.78 for placebo group , sd=2.81 for intervention group and a difference equal 1.4 ) .
taking in to account a drop - out rate of 30% we increased sample size to 33 in each group , which at the end of the study remained 29 and 31 persons in placebo and intervention groups , respectively .
inclusion criteria were non - smoking , aged 1845 years with body mass index > 30 kg / m and not trying to lose weight .
persons should not have endocrine causes of obesity , history of any medical illness , including hiv , diabetes , hepatic , renal or thyroid disease .
additional inclusion criteria were no medication , which would affect their plasma lipid levels , no treatment with blood dilutors , beta blockers , anti - inflammatory drugs and omega 3 or vitamin a supplements for the last 2 months .
the study protocol was approved by the medical ethics committee of the tabriz university of medical science ( code 901 ) .
the protocol and aims of the study were fully explained to the participants and all volunteers gave informed consent at the beginning of the study .
eligible participants were randomly assigned to receive either 1,000 mg of n-3lc pufa capsules containing 180 mg of epa and 120 mg of dha ( n=33 ) or 1,000 mg of paraffin as placebo ( n=33 ) twice a day for 4 weeks .
therefore , neither the participants nor the investigators were aware of treatment assignments in this double blind study [ figure 1 ] .
flowchart of subject screening and enrollment placebo was similar in size , color and shape to n-3lc pufa capsules .
the capsules were provided by zahravi pharmacy , tabriz , iran . at the beginning of the study some variables ( gender and bmi )
participants were instructed to consume the supplements with a meal and to maintain their usual dietary habits and physical activity during the study .
consumption of capsules was followed by phone in study duration and if they did not take more than 5 capsules was excluded .
blood samples were collected before and at the end of the study after 12 h fasting .
venous blood was drawn into edta tubes and within 1 h after the samples were taken centrifuged , and plasma was frozen at -70c until analyses were performed .
ppar  levels in plasma were determined using an elisa kit ( cusabio biotech co. , china ) according to the manufacturer s specifications .
total triiodothyronine ( t3 ) , thyroxine ( t4 ) and thyrotropin ( tsh ) were measured in plasma using an elisa kit ( monobind inc , usa ) .
weight and height measurements were performed at baseline and on 30 day of the study .
weight was measured without shoes using a carefully calibrated scale ( seca , germany ) and height was measured with use of wall - mounted calibrated meter scales .
the food intakes of participants were collected at the beginning and the end of the study using three 24-h dietary recalls . regarding the physical activity , all participants were in similar category .
all analyses were performed using statistical software minitab15 and spss15 for windows and p value of less than 0.05 was considered statistically significant .
this was a randomized , double - blind , placebo - controlled study in adults with obesity .
sixty six persons were recruited from a specialty and subspecialty clinic of tabriz university of medical science , tabriz , iran , by local advertisements .
the study was carried out from april to november 2011 . by considering 0.05% significant level and 95% power , from other studies ,
the maximum sample size was calculated 25 in each groups , based on t4 ( sd=1.78 for placebo group , sd=2.81 for intervention group and a difference equal 1.4 ) .
taking in to account a drop - out rate of 30% we increased sample size to 33 in each group , which at the end of the study remained 29 and 31 persons in placebo and intervention groups , respectively .
inclusion criteria were non - smoking , aged 1845 years with body mass index > 30 kg / m and not trying to lose weight .
persons should not have endocrine causes of obesity , history of any medical illness , including hiv , diabetes , hepatic , renal or thyroid disease .
additional inclusion criteria were no medication , which would affect their plasma lipid levels , no treatment with blood dilutors , beta blockers , anti - inflammatory drugs and omega 3 or vitamin a supplements for the last 2 months .
the study protocol was approved by the medical ethics committee of the tabriz university of medical science ( code 901 ) .
the protocol and aims of the study were fully explained to the participants and all volunteers gave informed consent at the beginning of the study .
eligible participants were randomly assigned to receive either 1,000 mg of n-3lc pufa capsules containing 180 mg of epa and 120 mg of dha ( n=33 ) or 1,000 mg of paraffin as placebo ( n=33 ) twice a day for 4 weeks .
therefore , neither the participants nor the investigators were aware of treatment assignments in this double blind study [ figure 1 ] .
flowchart of subject screening and enrollment placebo was similar in size , color and shape to n-3lc pufa capsules .
the capsules were provided by zahravi pharmacy , tabriz , iran . at the beginning of the study some variables ( gender and bmi )
participants were instructed to consume the supplements with a meal and to maintain their usual dietary habits and physical activity during the study .
consumption of capsules was followed by phone in study duration and if they did not take more than 5 capsules was excluded .
blood samples were collected before and at the end of the study after 12 h fasting .
venous blood was drawn into edta tubes and within 1 h after the samples were taken centrifuged , and plasma was frozen at -70c until analyses were performed .
ppar  levels in plasma were determined using an elisa kit ( cusabio biotech co. , china ) according to the manufacturer s specifications .
total triiodothyronine ( t3 ) , thyroxine ( t4 ) and thyrotropin ( tsh ) were measured in plasma using an elisa kit ( monobind inc , usa ) .
weight and height measurements were performed at baseline and on 30 day of the study .
weight was measured without shoes using a carefully calibrated scale ( seca , germany ) and height was measured with use of wall - mounted calibrated meter scales .
the food intakes of participants were collected at the beginning and the end of the study using three 24-h dietary recalls . regarding the physical activity , all participants were in similar category .
all analyses were performed using statistical software minitab15 and spss15 for windows and p value of less than 0.05 was considered statistically significant .
of all the participants , 60 participants finished the intervention ( n=31 in intervention group and n=29 in placebo group ) .
two of the participants receiving n-3lc pufa capsules and four participants in placebo group dropped out .
baseline characteristics of study participants ( n=60 ) clinical variables at baseline and after 4 weeks of intervention in two groups are shown in table 2 .
after 4 weeks of supplementation , there were no significant differences between the groups in ppar  levels ( p=0.972 ) .
clinical variables at baseline and after 4 weeks of intervention in two groups as shown in table 2 , plasma t3 , t4 and tsh levels in n-3lc pufa and placebo groups were 1.80  0.02 , 8.06  0.37 and 2.26  0.36 , respectively , after supplementation . among the thyroid hormones ,
t4 concentration was increased considerably over this period in the n-3lc pufa group but not in the placebo group ( p=0.009 ) .
however , there were no significant differences between the groups in the change in t3 and tsh .
although , their level was also increased in n-3lc pufa group but it was not statistically significant .
pufas act via nuclear receptors such as ppar  and thyroid hormones . in this study , we assessed the effect of epa and dha on plasma levels of ppar  , and thyroid hormones . as a result of our study [ table 2 ] , ppar  levels had no significant changes after 4 weeks .
no published data are available about the effects of n-3lc pufa supplementation on plasma ppar  levels in obesity in vivo .
for example , our results were similar to the study conducted by maclaren et al . which reported that epa supplementation by dose of 100 m for 24 h , had not significant effects on ppar  mrna levels in cultured bovine endometrial cells .
our result was also in line with the lack of effect of rosiglitazone , a potent activator of ppar  , and is also in agreement with previous results obtained in human fat cells .
on the other hand , li et al . reported that 10 mol / l epa and 100 mol / l dha increased ppar  mrna levels in hk-2 cells . in the other study ,
chambrier et al . showed that 50 m epa but not dha significantly increased ppar  mrna levels in human isolated adipocytes .
these authors suggest , therefore , that ppar  probably does not regulate the expression of its own gene in human adipocytes . in rodent adipose
cell lines , however , activation of ppar  with thiazolidinediones appeared to reduce ppar  expression , conflicting results from these studies suggesting that there may be species - related differences in the regulation of the ppar  gene in adipocytes .
the lack of effect of n-3lc pufa ( synthetic agonist of ppar ) on plasma ppar in this study might be a consequence of a low level of retinoid x receptor ( rxr ) , the partner of the ppars to form active heterodimers .
these ppar - rxr heterodimers bind to dna at direct repeats ( dr ) in promoters of many genes that regulate gene expression .
we did not assess differential effects of epa and dha and this is a limitation of our study .
the authors suggest that epa or dha may have a different effect on ppar gene expression and other researches are necessary in the future .
however , in this study , epa and dha did not induce a significant increase together in ppar  levels .
n-3lc pufa supplementation had no noticeable effect on plasma t3 and tsh but a significant increase in t4 concentration was observed in our study [ table 2 ] .
contradictory results are apparent in a study by souza et al . that 2 groups of rats consumed fish oil or soybean oil as an isocaloric and normolipid diets during lactation .
souza et al . suggested similar serum total t3 , t4 and tsh between 2 groups of rats . in knoop
study , animals were fed ad libitum the above basal diet with fish oil or cocoa butter . after 3 weeks of dietary treatment
, the findings of the same level of thyroid hormones - t4 and t3 - showed that there was no effect of fish oil supplementation on the thyroid function in rats .
t4 is the most abundant thyroid hormone , accounting for 80% , while t3 accounts for 20% of the thyroid hormones .
t4 significant changes in our observation may be due to its high levels in the blood .
trs bind to tr receptor ( tres ) not only as homodimers but also as heterodimers with other members of the receptor superfamily , such as rxrs .
heterodimerization with rxr dramatically increases the binding of trs to tres , the responsiveness of tr to t3 , and the transcriptional activation .
recently , it was shown that tr competes with ppar  for binding to dr1 as a heterodimer with rxr in vitro and in vivo to repress the transcriptional activity of ppar . thyroid receptors interact with ppars in part by sharing binding sites and heterodimeric partners such as rxr .
in summary , the present study shows that n-3lc pufas supplementation in obese adults resulted in higher t4 levels accompanied by no significant changes in t3 , tsh and ppar  plasma levels .
these findings suggest that the increase in thyroid hormone may be one of the mechanisms by which n-3lc pufas exert part of their effects in obesity .
first , we could not assess differential effects of epa and dha in this study and second was short duration of the intervention .
future studies are needed to show long - terms effects of n-3 lcpufas on ppar  in obesity .
first , we could not assess differential effects of epa and dha in this study and second was short duration of the intervention .
future studies are needed to show long - terms effects of n-3 lcpufas on ppar  in obesity .
 background : peroxisome proliferator - activated receptor gamma ( ppar  ) is a transcription factor , which is abundantly expressed in adipose tissue and has a direct link to adiposity . it seems that long - chain polyunsaturated fatty acids ( lc - pufas ) can regulate ppar  expression . 
 the purpose of this study was to investigate the effects of n-3lc pufa supplementation on plasma levels of ppar  and thyroid hormones in obesity.materials and methods : in a randomized double - blind controlled trial , 66 subjects with obesity were assigned to 2 groups . 
 participants in intervention group consumed omega3 capsules contained 1000 mg n-3 fatty acids ( 180 mg of eicosapentaenoic acid [ epa ] and 120 mg of docosahexaenoic acid [ dha ] ) and placebo group consumed placebo capsules contained paraffin twice a day for 4 wk . 
 fasting blood samples and weight measurements were collected at the baseline and at the end of the trial . 
 plasma ppar  and thyroid hormones were measured by elisa . 
 data were analyzed using a repeated measure model - two factor for comparing two groups in two times.results:no significant changes were observed in ppar  levels between and within the groups after supplementation ( p>0.05 ) . 
 n-3lc pufa supplementation significantly increased t4 levels after 4 wk ( p<0.05 ) but t3 and tsh did not change significantly.conclusion:our study showed that n-3lc pufas supplementation increased t4 levels . 
 however , no significant changes in t3 , tsh and ppar  plasma levels were observed in obese adults . 