Effect of substituting saturated with monounsaturated ...

International Journal of Food Sciences and Nutrition, November 2012; 63(7): 772–781

Effect of substituting saturated with monounsaturated fatty acids on serum visfatin levels and insulin resistance in overweight women: A randomized cross-over clinical trial

Int J Food Sci Nutr Downloaded from informahealthcare.com by Universitisi Putra Malaysia on 09/03/13 For personal use only.

FAHIMEH HAGHIGHATDOOST1, MOHAMMAD JAVAD HOSSEINZADEH-ATTAR1, AKRAM KABIRI1, MOHAMMADREZA ESHRAGHIAN2, & AHMAD ESMAILLZADEH3 1

Department of Nutrition and Biochemistry, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran, Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran, and 3 Department of Community Nutrition, School of Nutrition and Food Science, Food Security Research Center, Isfahan University of Medical Sciences, Isfahan, Iran 2

Abstract Objective: This study aimed to determine the effects of a monounsaturated fatty acids (MUFA)-rich diet on serum visfatin, interleukin-6 and insulin levels among overweight women. Design: In this randomized cross-over clinical trial, 17 premenopausal overweight women were included. Participants were randomly assigned to consume either a hypocaloric, saturated fatty acids (SFA)-rich diet (16% SFA and 8% MUFA) or a hypocaloric, MUFA-rich diet (16% MUFA and 8% SFA) for 12 weeks crossing over after a 2-week washout period. Percentages of energy from other macronutrients were similar between the two diets. Biochemical and anthropometric assessments were done at the first and at the end of each period. Statistical analyses were done using paired t-test. In all statistical analysis, p , 0.05 was considered as significant. Results: The participant’s mean body mass index was 27.6 kg/m2. Mean percentages of MUFA intake were 13% during MUFA-rich diet and 7% during SFA-rich diet. The corresponding values for SFA intake were 8.5% and 14%, respectively. We failed to find any significant differences between two intervention diets in terms of their effect on the serum levels of IL-6, visfatin and insulin. However, serum visfatin and IL-6 levels increased during the SFA-rich diet (0.4 ^ 0.4 ng/ml and 0.19 ^ 0.3 pg/ml, respectively) and decreased during the MUFA-rich diet (20.7 ^ 0.5 ng/ml and 20.17 ^ 0.3 pg/ml, respectively). In spite of a slight reduction in both periods, changes in serum insulin levels did not reach significant levels comparing the two periods. Conclusions: Our findings did not support any significant effect of a MUFA-rich intake on serum IL-6 and insulin levels as compared with a SFA-rich diet; however, it has the potential to favourably affect serum visfatin levels.

Keywords: visfatin, inflammation, MUFA, overweight, fatty acids, adipocytokines

Introduction Obesity, a proinflammatory condition, is a major public health problem in both developed and developing countries. Recent data indicated a growing prevalence of obesity as well as abdominal obesity worldwide (Popkin 2001; Ogden et al. 2006; Kelishadi 2007; Kelishadi et al. 2008). Nationally representative data from Iran have suggested that two-thirds of women and one-thirds of men are centrally obese (Azadbakht et al. 2005). Central obesity, which results from fat mass accumulation in the abdomen, has been

reported as a strong predictor for metabolic abnormalities (Janssen et al. 2004; Hotchkiss and Leyland 2010; Pajunen et al. 2011). Adipose tissue has been considered as the largest endocrine gland due to secretion of several adipocytokines (Vidal-Puig et al. 1996). These molecules have been at the centre of several studies in the last decade. Visfatin, the pre-b cell colony enhancing factor, is a newly detected adipocytokine secreted mainly by visceral adipose tissue (Fukuhara 2005) and in

Correspondence: Mohammad Javad Hosseinzadeh-Attar, Department of Nutrition and Biochemistry, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran. Tel: (þ98) 2188951395. Fax: (þ98) 2188951395. E-mail: [email protected] ISSN 0963-7486 print/ISSN 1465-3478 online q 2012 Informa UK, Ltd. DOI: 10.3109/09637486.2012.665044


MUFA-rich diet and adipocytokines a lower amount by other tissues such as skeletal muscle, liver, bone marrow and lymphocytes (Ognjanovic 2001). Visfatin gene expression increases by IL-6 (Fukuhara 2005; Sethi and Vidal-Puig 2005). A positive relationship has been found between the stimulation of peroxisome proliferator-activated receptor g (PPAR-g) and serum visfatin levels (Choi et al. 2005; Storka et al. 2008; Li et al. 2009). Visfatin has paracrine/autocrine and endocrine roles. In terms of paracrine/autocrine role, it promotes the development and differentiation of adipose tissue, while in its endocrine role, it has an insulin-mimetic function (Sethi and Vidal-Puig 2005). Visfatin has also been found to have a proinflammatory feature (Fukuhara 2005) and induces insulin resistance. Its elevated serum levels have been shown in obesity, type 2 diabetes and insulin resistance syndrome (Klebanova et al. 2007; Rodrı´guez et al. 2007; Baranova 2008; Al-Dokhi 2009; Ikeoka et al. 2010). Dietary determinants of body fat distribution and serum adipocytokine levels are not well understood. Dietary fatty acids have long been as a sole focus of several studies in this field. Current evidence suggests that dietary intake of monounsaturated fatty acids (MUFA) stimulates peripheral and prevents central fat accumulation, while dietary saturated fatty acids (SFA) stimulates central fat accumulation (Piers et al. 2003). Dietary intake of fatty acids might modify gene expression (Duplus et al. 2000), metabolism and secretion (Flachs et al. 2006) of adipocytokines from adipose tissue. Dietary MUFA intake might affect serum visfatin and IL-6 levels by its stimulating effect on PPAR-g (Sanderson et al. 2008) or its favourable effect on visceral fat accumulation (Piers et al. 2003). So far, few studies were undertaken to assess the effect of different macronutrients on serum adipocytokine levels. These studies have reported that dietary fatty acids composition might influence adipocytokine levels independent of weight loss (van Dijk et al. 2009). For instance, an inverse association between fruit, vegetable and fibre consumption and serum IL-6 levels has been shown (Ma et al. 2008). Western dietary pattern (containing high amounts of red and processed meat, high-fat dairy products, butter, refined grain and sweet) has been associated with elevated levels of serum IL-6 and other cytokines (Lopez-Garcia et al. 2004; Esmaillzadeh et al. 2007; Esmaillzadeh and Azadbakht 2008). Moreover, a favourable effect of MUFA consumption on serum levels of adiponectin (Paniagua et al. 2007a,b), leptin (Soriguer et al. 2003) and IL-6 (Han et al. 2002; Aeberli et al. 2006; van Dijk et al. 2009) or their gene expression has been reported. High SFA intake was found to act as a down-regulator of adiponectin gene expression (Matsuzawa et al. 2004) and inducer of proinflammatory status by enhancing serum IL-6 levels (van Dijk et al. 2009). However, few studies have assessed the dietary determinants of adiponectin, leptin, IL-6 and visfatin levels. To the best of our

773

knowledge, there is no randomized cross-over clinical trial assessing the effect of dietary factors on serum visfatin levels, and available data are very limited (de Luis et al. 2010; Siahanidou et al. 2011). This study aimed to examine the effects of substitution SFA with MUFA on serum visfatin, IL-6 and insulin levels among overweight women. Subjects and methods Subjects This single-blind and randomized cross-over trial was conducted among overweight (25 # body mass index (BMI) # 29.9 kg/m2) premenopausal women aged 20– 50 years. All subjects expressed their willingness to participate in the study by providing a written informed consent. Participants were apparently healthy and free of chronic diseases (coronary heart disease, diabetes mellitus, gastro-intestinal disorders, arthritis rheumatoid, trauma, infection, hypothyroidism or hyperthyroidism). Not using medications such as non-steroidal anti-inflammatory drugs, corticosteroids, oral contraceptive pills, oral hypoglycaemic and weight- or satietyreducing agents was another criterion for inclusion in the study. Required sample size for the study was determined using serum visfatin level as the principal dependent variable (Lee et al. 2010) by using the formula n ¼ ððZ ð12ða=2ÞÞ þ Z 12b Þ=2dÞ2 . A total of 26 volunteers enrolled in the study and 17 individuals completed the randomized cross-over trial (Figure 1). Nine participants dropped out within the study because of poor compliance (n ¼ 5), surgery (n ¼ 1) and excess weight loss (n ¼ 1). Two participants were excluded from the study due to missing data. No significant differences were found between those dropped out and those remained in the study in terms of age and other variables. The study was approved by the ethical committee of Tehran University of Medical Sciences, Tehran, Iran and has been registered (IRCT138812223550N1) at Iranian web site for clinical trials (www.irct.ir). Study design To obtain more accurate information about habitual dietary intakes and physical activity patterns of participants, a 10-day run-in period was considered before the start of the trial. A 3-day food diary as well as physical activity records was taken from each participant during this period. At the end of run-in period, participants were randomly assigned by using computer-based software to consume either a SFA-rich diet or MUFA-rich diet (explained below) in a random order, each during two 6-week periods separated by a 2-week washout period. Because all subjects were overweight, we prescribed calorie-restricted diets (2500 kcal) for both groups. The caloric needs were individually estimated according to equations suggested by the

774 F. Haghighatdoost et al.

Screened for eligibility (n = 38)

Did not meet inclusion criteria (n = 7)

Run-in period (10 days) Randomized (n = 26)


MUFA-rich diet (n = 13)

Intervention (6 weeks)

Washout (2 weeks)

Intervention (6 weeks)

Withdrawn due to poor compliance (n = 3)

Refused to participate (n = 5)

Iranian-usual diet (n = 13)


End of first phase (n = 10)

End of first phase (n = 12)

Did not continue the trial (n = 2)

Withdrawn due to surgery (n = 1)

Started the second phase (n = 10)

Started the second phase(n = 9)

Withdrawn due to excess weight loss (n = 1)


End of second phase (n = 9)

End of second phase (n = 8)

Completed the trial (n = 17) Figure 1. Diagram of the study. Among 38 subjects, 26 participants enrolled in the study and were randomly assigned to two groups. Ultimately, the study ended up with 17 participants. SFA-rich diet: an energy-restricted diet that contained 15% of energy from protein, 51% from carbohydrate and 34% from total fat (16% SFA, 8% MUFA and 10% polyunsaturated fatty acid). MUFA-rich diet: an energy-restricted diet that contained 15% of energy from protein, 51% from carbohydrate and 34% from total fat (8% SFA, 16% MUFA and 10% polyunsaturated fatty acid).

Institute of Medicine, Food and Nutrition Board (2002). All volunteers received an exchange list and education in substituting food items and were also educated how to write food diaries. Subjects were asked to keep their physical activity level constant during the study. Anthropometric and biochemical assessments were done before and after of each intervention period. Diets The prescribed diets (SFA- and MUFA-rich diets) were similar in their macronutrient composition, except for MUFA and SFA content. Both diets contained 15% protein, 51% carbohydrate and 34% fat. Dietary polyunsaturated fatty acid (PUFA) composition of both diets was 10% of total energy.

During MUFA-rich intervention phase, participants were prescribed a diet with 16% MUFA (mainly in the form of extra virgin olive oil) and 8% SFA while in the SFA-rich diet intervention phase, 8% MUFA and 16% SFA (according to usual amounts of SFA intake among Iranians (Kalantary and Ghafarpoor 2005)) were included. The dietary SFA in SFA-rich diet was provided by the use of high-fat dairy products, butter and red meat and it was restricted during MUFA-rich diet by inclusion of low-fat dairy products, fish and poultry in the menus. Seven-day cycle menus were created for each diet based on individualized requirements of each participant. These menus were evaluated for nutrient and particularly fatty acid content using food composition database (Dorosti and Tabatabaei 2007).

MUFA-rich diet and adipocytokines All participants were visited every 2 weeks. In order to assess compliance of the prescribed diets, six 1-day food records were provided by each participant during weeks 2, 4, 6, 8, 10 and 12. Analysis of energy and different macronutrient content of dietary records were done using the NUTRITIONIST IV software (version 7.0; N-Squared Computing, Salem, OR, USA) which was modified for Iranian food items. The extra virgin olive oil was freely provided for all subjects.


Anthropometric assessment Height was assessed by a wall-mounted tape measure while the subjects were without shoes in a normal standing position and recorded to the nearest 0.5 cm. Body weight, fat and fat free mass were measured by using a TANITA-418MA body composition analyser (Tanita, Tokyo, Japan), while participants were light clothing without shoes. Body weight was recorded to the nearest 100 g. BMI was calculated as weight in kilograms divided by height in metres squared. Waist and hip circumferences were measured over light clothing using a metal tape measure without imposing any pressure to body surface and were recorded to the nearest 0.5 cm. The location for measuring waist circumference was considered as the narrowest level between the lowest rib and iliac crest and for hip circumference was defined as the largest circumference. All measurements were done after an overnight fast. The physical activity levels were assessed using daily records and were expressed as metabolic equivalent-hours per day (MET-h/d; Ainsworth et al. 2000). Biochemical assessment To measure biochemical indices, 10 ml venous blood samples were taken after a 12-h overnight fasting. Concentrations of plasma glucose and serum lipid profiles were assessed using commercially available enzymatic reagents (Pars Azmoon, Tehran, Iran) adapted to a Selectra-2 autoanalyzer (Vital Scientific, Spankeren, The Netherlands). Fasting plasma glucose, total- and HDL-cholesterol and triacylglycerol levels were assessed via enzymatic (oxidase enzyme of each marker) colorimetric method. Both interand intra-assay coefficients of variability (CVs) for glucose, total- and high-density lipoprotein (HDL)cholesterol and triacylglycerol were less than 5%. Serum low-density lipoprotein (LDL)-cholesterol was measured directly after precipitating of HDL- and very low-density lipoprotein (VLDL)-cholesterol and chylomicrons via an enzymatic colorimetric technique using commercial kits. Inter- and intra-assay CVs for LDL-cholesterol were 1.37% and 0.65%, respectively. Serum insulin levels were quantified using enzymelinked immunosorbent assay (ELISA) method (ELISA; Diagnostic Biochem Canada, Inc., Montreal, Canada). Intra- and inter-assay CVs for insulin were

775

lower than 10% which calculated using a duplicate study sample. Insulin resistance was estimated on the basis of fasting glucose and insulin levels, using the Homeostasis Model Assessment (HOMA-IR) method (Matthews et al. 1985). Serum visfatin and IL-6 levels were also measured by the use of ELISA by means of commercially available kits (ELISA; Adipogen (twin plex), Seoul, Korea; and Diaclone, Paris, France respectively). Inter- and intra-assay CVs for visfatin were 5.9% and 5.6%, respectively, whereas for IL-6 the corresponding values were 9.1% and 4.4%, respectively. To evaluate blood pressure, participants were initially made to rest for 15 min. Then a qualified person measured blood pressure two times during physical examinations in a seated position after one initial measurement for determining peak inflation level using a standard mercury sphygmomanometer. There was at least 30 s interval between these two separate measurements, and thereafter the mean of two measurements was considered as the participant’s blood pressure. Before measuring blood pressure, the participant was questioned about drinking tea or coffee, physical activity, smoking and full bladder. Statistical analysis Statistical analysis was done on 17 subjects who completed the study. We used Kolmogorov–Smirnov test and histogram to ensure the normal distribution of variables. General characteristics of the study participants were expressed as means or percentages by the use of descriptive statistics. For each variable, we computed the changes by subtracting the baseline value from the end-of-trial value. Changes in biochemical markers, anthropometric measurements and food intakes between the two periods were compared using paired t-test. To adjust for some differences between the two groups, we used generalized linear model analysis of covariance in different models taking into account time and diet type. First, we checked for the interaction terms between time (before and after) and diet type. No significant interactions were found. In model 1, we adjusted for dietary fibre and PUFA intake. Additional controlling was made for dietary protein intake in model 2. Further adjustments for changes in fat mass, insulin and fasting plasma glucose were done in other models to ascertain whether the effect of diets on adipocytokine levels is independent of these changes. All statistical analyses were done by Statistical Package for Social Sciences (SPSS, Inc., Chicago IL, USA; version 18). P , 0.05 was considered significant in all statistical analyses. Results The participant’s mean age (^ SD) was 34.8 (^ 7.9) years and their mean BMI was 27.6 kg/m2. The baseline waist circumference and fat mass were


776 F. Haghighatdoost et al. 79.7 ^ 5.8 cm and 23.4 ^ 2.6 kg, respectively. The physical activity level of the participants did not change across the study periods (mean (^ SE) physical activity level in usual diet: 1.45 ^ 0.16 MET-h/d; and in MUFA-rich diet: 1.46 ^ 0.14 MET-h/d; p ¼ 0.9). Mean dietary macronutrient intakes of participants are shown in Table I. Findings from dietary records indicated that mean percentages of MUFA intake was 13% during MUFA-rich diet and 7% during SFA-rich diet. The corresponding values for SFA intake was 8.5% and 14%, respectively. The mean energy intake was 1782 kcal/d during SFA-rich diet period and 1812 kcal/d during MUFA-rich diet period. No significant differences in dietary carbohydrate and total fat intake were found between the two intervention periods, whereas the differences in dietary MUFA ( p , 0.001), SFA ( p , 0.001) and PUFA ( p , 0.002) intake were statistically significant and protein intake was marginally significant ( p ¼ 0.05). Participants consumed significantly more dietary fibre during the period of MUFA-rich diet than that they did during the SFA-rich diet period ( p ¼ 0.02). The effect of the two prescribed diets on anthropometric measures is shown in Figure 2. A significant reduction was observed in body weight, BMI, waist circumference, fat mass and fat-free mass during both phases but comparing MUFA-rich diet with SFA-rich diet, the differences were non-significant. The mean percentage of all changes was less than 5%, except for fat mass which decreased 5.9% during SFA-rich diet and 8.3% during MUFA-rich diet ( p ¼ 0.23). Both SFA- and MUFA-rich diets resulted in a moderate reduction in fasting plasma glucose (23.7 ^ 1.9 vs. 24.3 ^ 1.4 mg/dl; p ¼ 0.7), serum total cholesterol (29.7 ^ 4.8 vs. 214.3 ^ 4.8 mg/dl; p ¼ 0.5), triacylglycerol (2 39.9 ^ 21.8 vs. 2 41.3 ^ 10.7 mg/dl; p ¼ 0.9) and LDL-cholesterol (23.1 ^ 4.7 vs. 26.3 ^ 3.2 mg/dl; p ¼ 0.5) and a slight

increment in HDL-c (1.6 ^ 1.7 vs. 0.2 ^ 2.2 mg/dl; p ¼ 0.6) levels, but no significant differences were observed comparing the two intervention phases. Systolic blood pressure decreased 7 mmHg during consumption of SFA-rich diet and 4 mmHg during the period of MUFA-rich diet ( p ¼ 0.9). Diastolic blood pressure increased moderately during two phases (4 mmHg during SFA-rich diet and 1 mmHg during MUFA-rich diet; p ¼ 0.7). Table II indicates the effects of two prescribed diets on serum visfatin and IL-6 levels. We failed to find any significant differences between the two intervention diets in terms of their effect on the serum levels of these adipocytokines. However, serum visfatin and IL-6 levels increased during the period of SFA-rich diet (0.4 ^ 0.4 ng/ml and 0.19 ^ 0.3 pg/ml, respectively) and decreased during the period of MUFA-rich diet (2 0.7 ^ 0.5 ng/ml and 2 0.17 ^ 0.3 pg/ml, respectively). After adjustment for dietary fibre and PUFA intake in model 1 and additional adjustments for protein intake in model 2 and further for fat mass in model 3, no alterations in findings occurred. Further adjustment for circulating insulin and glucose levels in separate models (4 and 5, respectively) did not affect the findings either. The effects of consuming SFA- and MUFA-rich diet on serum insulin levels are provided in Table III. In spite of a slight reduction in both periods, changes in serum insulin levels did not reach significant levels comparing the two periods. After adjustment for several confounders, including dietary fibre, PUFA and protein intakes, this finding remained non-significant. The effect of SFA- and MUFA-rich diet on HOMA-IR score is shown in Figure 3. Although both prescribed diets resulted in a reduced HOMA-IR score, but we did not find any significant differences between them (2 0.152 ^ 0.198 vs. 2 0.256 ^ 0.165 (MicU/ml)(mmol/l), respectively; p ¼ 0.7).

Table I. The mean ^ SE of macronutrient consumption during the two intervention periods*.

SFA-rich diet† (n ¼ 17)

Energy (kcal/d) Total fat (g/d) SFA§ (g/d) MUFA§ (g/d) PUFA§ (g/d) Carbohydrate (g/d) Protein (g/d) Fibre (g/d)

MUFA-rich diet‡ (n ¼ 17)

Differences between the two diets{ (n ¼ 17)

Mean

SE

Percentage of energy

Mean

SE

Percentage of energy

Mean

SE

p

1781 65.5 27.2 14.1 21.0 224.0 63.4 16.6

25.8 1.1 0.83 0.74 1.4 4.2 1.7 0.9

– 33 14 7 10.6 50.2 14.2 2

1812 63.4 17.3 25.5 15.3 235.1 69.0 19.8

21.5 1.7 0.58 0.83 0.89 5.8 2.1 0.94

– 31.5 8.5 13 7.5 52 15.2 2

33 22.1 210.0 11.4 25.7 11.1 5.4 3.2

33.5 1.1 1.01 1.1 1.6 7.1 2.7 1.3

0.3 0.5 ,0.001 ,0.001 0.002 0.1 0.05 0.02

† * Paired t-test; SFA-rich diet: an energy-restricted diet that contained 15% of energy from protein, 51% from carbohydrate and 34% from total fat (16% SFA, 8% MUFA and 10% polyunsaturated fatty acid); ‡ MUFA-rich diet: an energy-restricted diet that contained 15% of energy from protein, 51% from carbohydrate and 34% from total fat (8% SFA, 16% MUFA and 10% polyunsaturated fatty acid); { Calculated by subsidizing the values of SFA-rich diet from values of MUFA-rich diet; § SFA: saturated fatty acid; MUFA: monounsaturated fatty acid; PUFA: polyunsaturated fatty acid.

MUFA-rich diet and adipocytokines A

Body weight

Baseline End of trial

68

B

67 kg

kg

66 65 64 63 62 SFA C

28.5

SFA

MUFA

Body mass index


D

kg

kg/m2

27.5 27.0 26.5 26.0

SFA

MUFA

MUFA Fat free mass

43.4 43.2 43.0 42.8 42.6 42.4 42.2 42.0 41.8 41.6 41.4



MUFA

Waist circumference

E

cm


28.0

SFA

Fat mass 25.0 24.5 24.0 23.5 23.0 22.5 22.0 21.5 21.0 20.5

777


81.0 80.5 80.0 79.5 79.0 78.5 78.0 77.5 77.0 76.5 SFA

MUFA

Figure 2. The effect of MUFA-rich and SFA-rich diet on anthropometric measures. SFA-rich diet: An energy-restricted diet that contained 15% of energy from protein, 51% from carbohydrate and 34% from total fat (16% SFA, 8% MUFA and 10% polyunsaturated fatty acid). MUFA-rich diet: An energy-restricted diet that contained 15% of energy from protein, 51% from carbohydrate and 34% from total fat (8% SFA, 16% MUFA and 10% polyunsaturated fatty acid). The differences between the two diets were not significant.

Discussion In this randomized cross-over clinical trial, we did not find any significant differences between MUFA- and SFA-rich diets in terms of their effect on serum visfatin, IL-6 and insulin levels among overweight women. Although few studies have reported the effects of MUFA-rich diet on serum visfatin, IL-6 and insulin levels, to the best of our knowledge, this study is the first randomized cross-over clinical trial examining the effect of a MUFA-rich diet on serum visfatin levels. Many studies have demonstrated the beneficial effects of weight loss on inflammatory mediators and adipocytokines (Gallistl et al. 2001; Nicklas et al. 2004), controversial information is available about serum visfatin responses to weight loss (Kovacikova et al. 2008; Sheu et al. 2008; Lee et al. 2010). Discrepancy in findings might be attributed to different dietary compositions, and particularly dietary fatty acid composition, used in different studies. In the current study, consumption of a MUFA-rich diet as compared with a SFA-rich diet did not

significantly influence anthropometric measurements and metabolic profiles. Data on the effect of MUFA consumption on anthropometric measures (Mata et al. 1992; Williams et al. 1999; Vessby et al. 2001; Rasmussen et al. 2007; Moussavi et al. 2008a,b) and metabolic profiles (Piers et al. 2003; Brunerova et al. 2007; Paniagua et al. 2007a,b; Due et al. 2008; Bos et al. 2010) are largely inconsistent which might be resulted from the differences in study design, the amount of MUFA consumed or even the duration of intervention. In this study, serum insulin levels were not affected by high MUFA intake. The same findings have also been reported by other studies (Piers et al. 2003; Paniagua et al. 2007a,b; Bos et al. 2010). However, some investigations have found a favourable effect of MUFA intake on serum insulin levels (Due et al. 2008). It must be kept in mind that such studies have used a higher dosage of MUFA (Piers et al. 2003; Paniagua et al. 2007a,b) as compared with the current study (20% vs. 16%). Furthermore, larger sample sizes and longer duration of these studies might

778 F. Haghighatdoost et al. Table II. The effects of MUFA-rich and SFA-rich diet on serum visfatin and IL-6 levels among overweight women*.


SFA-rich diet† (n ¼ 17)

IL-6 (pg/ml) Crude Model Ik Model II# Model III** Model IV†† Model V‡‡ Visfatin (ng/ml) Crude Model I Model II Model III Model IV Model V


Baseline

End of trial

Changes{

Baseline

End of trial

Changes

p§

0.67 ^ 0.8 0.62 ^ 0.2 0.49 ^ 0.2 0.50 ^ 0.2 0.80 ^ 0.2 0.70 ^ 0.2

0.86 ^ 1.0 0.62 ^ 0.2 0.6 ^ 0.2 0.6 ^ 0.2 0.9 ^ 0.2 0.9 ^ 0.2

0.19 ^ 0.3 0.004 ^ 0.3 0.15 ^ 0.3 0.09 ^ 0.3 0.16 ^ 0.3 0.17 ^ 0.3

0.79 ^ 1.0 0.85 ^ 0.2 0.97 ^ 0.2 0.9 ^ 0.2 0.8 ^ 0.3 0.8 ^ 0.2

0.62 ^ 0.8 0.84 ^ 0.2 0.8 ^ 0.2 0.8 ^ 0.2 0.6 ^ 0.2 0.6 ^ 0.2

20.17 ^ 0.3 20.17 ^ 0.3 20.12 ^ 0.3 20.07 ^ 0.3 20.14 ^ 0.3 20.15 ^ 0.3

0.4 0.9 0.6 0.7 0.7 0.5

20.7 ^ 0.5 20.7 ^ 0.2 20.74 ^ 0.5 20.8 ^ 0.5 20.8 ^ 0.5 20.7 ^ 0.5

0.08 0.1 0.1 0.1 0.1 0.2

1.4 ^ 0.9 1.4 ^ 0.39 1.4 ^ 0.4 1.5 ^ 0.4 1.4 ^ 0.2 1.4 ^ 0.2

1.8 ^ 1.6 1.8 ^ 0.35 1.8 ^ 0.3 2.0 ^ 0.3 1.8 ^ 0.3 1.8 ^ 0.3

0.4 ^ 0.4 0.41 ^ 0.4 0.42 ^ 0.5 0.4 ^ 0.5 0.4 ^ 0.5 0.4 ^ 0.5

2.0 ^ 1.8 1.9 ^ 0.39 2.0 ^ 0.4 1.8 ^ 0.4 2.0 ^ 0.5 2.0 ^ 0.5

1.3 ^ 0.9 1.2 ^ 0.35 1.2 ^ 0.35 1.1 ^ 0.3 1.3 ^ 0.3 1.3 ^ 0.3

† * All values are mean ^ SEM; An energy-restricted diet that contained 15% of energy from protein, 51% from carbohydrate and 34% from total fat (16% SFA, 8% monounsaturated fatty acid and 10% polyunsaturated fatty acid); ‡ MUFA-rich diet: an energy-restricted diet that contained 15% of energy from protein, 51% from carbohydrate and 34% from total fat (8% SFA, 16% monounsaturated fatty acid and 10% polyunsaturated fatty acid); { Calculated by subsidizing the values of SFA-rich diet from values of MUFA-rich diet; § For the comparison of mean changes between the two diets by paired t-test; k Model I: adjusted for dietary PUFA and fibre intake; # Model II: additionally adjusted for protein intake; ** Model III: further adjusted for fat mass changes; †† Model IV: further adjustment for insulin changes; ‡‡ Model V: additional adjustment for blood glucose changes.

provide additional reasons for such discrepancies (Bos et al. 2010). Limited information is available indicating the effects of MUFA-rich diet on IL-6 changes compared with SFA-rich diet. These limited studies, which mainly focused on IL-6 gene expression, have suggested a beneficial effect of MUFA intake on this inflammatory biomarker, while indicated SFA as an inflammation-inducing dietary agent which induces the gene expression of inflammatory mediators (van Dijk et al. 2009). In our study, despite the reduction in serum IL-6 levels during MUFA-rich diet and its increment during SFA-rich diet period, we did not find statistically significant difference between the two diets in terms of their effect on serum IL-6 levels. The up-regulating effects of SFA intake on inflammatory mediators gene expression have been shown by previous studies (van Dijk et al. 2009).

The effects of diet-induced weight loss on serum visfatin levels have been reported by several studies with inconsistent findings (Kovacikova et al. 2008; Sheu et al. 2008; Lee et al. 2010). In the current study, we observed different responses of serum visfatin levels to weight loss in the two prescribed diets. Serum visfatin levels increased during SFA-rich diet and decreased during MUFA-rich diet. These findings underscore the importance of dietary macronutrients composition on responses of serum visfatin levels to weight loss and might explain the inconsistent results of the effect of weight loss on serum visfatin levels. Our results provide evidence indicating that MUFA consumption tended to reduce serum visfatin levels in premenopausal overweight women as compared with SFA intake. Inadequate sample size, limited duration of intervention and relatively moderate amounts (rather than high amounts) of MUFA intake

Table III. The effects of MUFA-rich and SFA-rich diet on serum insulin levels among overweight women*. SFA-rich diet† (n ¼ 17)

Insulin (mlU/ml) Crude Model Ik Model II# Model III** Model IV††


Baseline

End of trial

Changes{

Baseline

End of trial

Changes

p§

8.6 ^ 0.9 8.5 ^ 1.0 8.5 ^ 1.0 9.0 ^ 1.0 8.5 ^ 1.1

8.3 ^ 0.7 8.2 ^ 0.7 8.2 ^ 0.7 8.3 ^ 0.7 8.2 ^ 0.7

20.3 ^ 0.9 20.5 ^ 1.0 20.3 ^ 1.0 20.7 ^ 1.0 20.3 ^ 1.0

8.5 ^ 0.9 8.3 ^ 1.0 8.6 ^ 1.0 8.0 ^ 1.0 8.6 ^ 1.1

7.6 ^ 0.7 7.7 ^ 0.7 7.7 ^ 0.7 7.6 ^ 0.7 7.8 ^ 0.7

20.9 ^ 0.9 20.6 ^ 1.0 20.9 ^ 1.0 20.4 ^ 1.0 20.8 ^ 1.0

0.6 0.9 0.7 0.8 0.7

† * All values are mean ^ SEM; An energy-restricted diet that contained 15% of energy from protein, 51% from carbohydrate and 34% from total fat (16% SFA, 8% monounsaturated fatty acid and 10% polyunsaturated fatty acid); ‡ MUFA-rich diet: an energy-restricted diet that contained 15% of energy from protein, 51% from carbohydrate and 34% from total fat (8% SFA, 16% monounsaturated fatty acid and 10% polyunsaturated fatty acid); { Calculated by subsidizing the values of SFA-rich diet from values of MUFA-rich diet; § For the comparison of mean changes between the two diets by paired t-test; k Model I: adjusted for dietary PUFA and fibre intake; # Model II: additionally adjusted for protein intake; ** Model III: further adjusted for fat mass changes; †† Model IV: additional adjustment for blood glucose changes.

MUFA-rich diet and adipocytokines HOMA-IR 0.00

(Mic U/ml)(mmol/l)

–0.05 –0.10 –0.15 –0.02

SFA MUFA

–0.25


–0.30 Figure 3. The effect of SFA- and MUFA-rich diet on insulin resistance. SFA-rich diet: an energy-restricted diet that contained 15% of energy from protein, 51% from carbohydrate and 34% from total fat (16% SFA, 8% MUFA and 10% polyunsaturated fatty acid). MUFA-rich diet: an energy-restricted diet that contained 15% of energy from protein, 51% from carbohydrate and 34% from total fat (8% SFA, 16% MUFA and 10% polyunsaturated fatty acid). The differences between the two diets were not significant.

in our study might explain why we could not reach significant findings in this regard. The mechanisms by which dietary fatty acids influence serum inflammatory biomarkers remain to be elucidated. Nuclear factor-kB (NF-kB) may provide a molecular mechanism whereby dietary fatty acids modulate inflammation process (Bellido et al. 2004). Indeed, the stimulation of NF-kB by SFA, but not MUFA (Bellido et al. 2004) may lead to induction of IL-6 secretion (Nomi et al. 2010) and consequently the increased gene expression of visfatin (Fukuhara 2005; Sethi and Vidal-Puig 2005). It has been shown that the proinflammatory characteristic of visfatin is mediated by stimulating NF-kB (Oita et al. 2010). Therefore, NF-kB stimulation by SFA leads to the progression of the cycle, while MUFA intake would break this cycle. Furthermore, MUFA intake prevents the visceral fat accumulation (Piers et al. 2003), the original source of visfatin secretion, which could in turn lead to the decrease in serum visfatin levels. Another suggested mechanism is their effects on PPARs (Sanderson et al. 2008), especially PPAR-g. Although the stimulation of PPAR-g is associated with elevated serum visfatin levels in diabetic subjects (Choi et al. 2005; Storka et al. 2008; Li et al. 2009), such findings have not been reported in non-diabetics (Deans et al. 2009). Hence, consumption of MUFA, a better ligand for PPARs rather than SFA, would prohibit the production of visfatin by visceral fat cells. Furthermore, some studies have indicated that the stimulation of PPAR-g is associated with downregulation of inflammatory process (Sharma and Staels 2007) which provides another possible mechanism through which dietary fats affect inflammation. Despite of several strengths, some limitations must also be taken into account when interpreting our

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findings. The main limitation of this study might be inadequate sample size. However, the randomized cross-over design of the study must be kept in mind because the cross-over trials need small sample sizes. Other published randomized cross-over clinical trials have also enrolled the same sample size or even smaller than the one in our study (Piers et al. 2003; Paniagua et al. 2007a,b). Furthermore, for calculation of sample size, we used the suggested formula for cross-over trials by considering the power of the study as 80%. Lack of finding significant effects of MUFA-rich diet in the current study might be attributed to the limited duration of the intervention. We used dietary records as a method of assessing compliance in this study. Others have suggested the use of biomarkers like fatty acid profiles in adipose tissue or in red blood cell or membrane phospholipids content. Due to budget limitation, we could not consider the biochemical markers as an indicator of diet compliance. In conclusion, our findings suggest a within group significant reduced visfatin levels among those consume a hypocaloric MUFA-rich diet in contrast with elevated levels among consumers of a hypocaloric SFA-rich diet. In this study, we did not find any significant effect of a MUFA-rich intake on serum IL6 and insulin levels as compared with a SFA-rich diet; however, MUFA-rich diet has the potential to favourably affect serum visfatin levels. Due to the proinflammatory characteristic of these adipocytokines and their association with obesity-related comorbidities, designing longitudinal studies with large sample size is warranted. Declaration of interest: This study was funded by Tehran University of Medical Sciences (TUMS), Tehran, Iran. The authors would like to express their appreciation to the Research Council of TUMS for financial support of the study. The authors report no conflict of interest. The authors alone are responsible for the content and writing of the paper. Contribution of authors: FH involved in conception, design, data collection, statistical analysis and data interpretation. ME participated in the statistical analysis. AK involved in data collection, statistical analysis and data interpretation. MHA and AE involved in conception, design and statistical analysis. All authors contributed in manuscript drafting and approval of final manuscript for submission. MHA and AE supervised the study.

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