|Year : 2018 | Volume
| Issue : 2 | Page : 69-76
Response of lipids, estradiol level, and liver size to diet and high-intensity interval training in postmenopausal women with fatty liver
Abeer M ElDeeb1, Hany F Elsisi2, Yasser R Lasheen3
1 Department of Physical Therapy for Women’s Health, Cairo University, Giza, Egypt
2 Department of Physical Therapy for Cardiovascular/Respiratory Disorder and Geriatrics, Cairo University, Giza, Egypt
3 Basic Science, Faculty of Physical Therapy, Cairo University, Giza, Egypt
|Date of Submission||21-Mar-2018|
|Date of Acceptance||12-Aug-2018|
|Date of Web Publication||27-Dec-2018|
Abeer M ElDeeb
Department of Physical Therapy for Women’s Health, Faculty of Physical Therapy, Cairo University, 7 Ahmed El-Zayat Street, Bein El-Sarayat, Dokki, Giza 12622
Source of Support: None, Conflict of Interest: None
Background Menopause is associated with changes in body composition and distribution, as well as reduced estradiol level that affect the development and progression of fatty liver diseases.
Aims To determine anthropometric measurements, lipid and estradiol levels, and size of liver in response to diet and high-intensity interval training (HIIT) in postmenopausal women with hepatic steatosis.
Setting and design A single blind, randomized controlled trial was conducted on a total of 56 postmenopausal women with hepatic steatosis.
Patients and methods Participants were randomized to one of two groups. Diet group consisting of 30 patients received hypocaloric diet for 12 weeks, while diet–HIIT group consisting of 26 patients received hypocaloric diet and HIIT three times/week for 12 weeks. Anthropometric measurements including weight, BMI, and waist girth were taken. Blood samples were collected to determine the levels of lipids, including total cholesterol, triglycerides (TGs), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol, as well as estradiol level. Also, ultrasonography was used to measure the liver size. All outcomes were measured at starting and after 12 weeks of the treatment course.
Results The diet–HIIT group showed a greater decrease in the waist girth (0.0001), TG (P=0.002), and liver size (P=0.005), as well as a greater increase in HDL-C (P=0.03) and estradiol level (P<0.0001) than the diet group. Linear regression analysis showed that the mean change in estradiol level accounted for 52% of variability in the liver size.
Conclusion Hypocaloric diet–HIIT intervention is a more effective treatment for improving waist girth, HDL-C, TGs, estradiol level, and liver size than hypocaloric diet alone. The mean change of estradiol level is a significant predictor for improving liver size in obese postmenopausal women with hepatic steatosis.
Keywords: diet, fatty liver, high-intensity interval training
|How to cite this article:|
ElDeeb AM, Elsisi HF, Lasheen YR. Response of lipids, estradiol level, and liver size to diet and high-intensity interval training in postmenopausal women with fatty liver. Bull Fac Phys Ther 2018;23:69-76
|How to cite this URL:|
ElDeeb AM, Elsisi HF, Lasheen YR. Response of lipids, estradiol level, and liver size to diet and high-intensity interval training in postmenopausal women with fatty liver. Bull Fac Phys Ther [serial online] 2018 [cited 2020 Nov 28];23:69-76. Available from: http://www.bfpt.eg.net/text.asp?2018/23/2/69/248789
| Introduction|| |
Nonalcoholic fatty liver disease (NAFLD) is one of the most common liver diseases worldwide . NAFLD is a broad term that has been used to describe a spectrum of liver pathology. Although hepatic steatosis is typically considered as a benign condition, it can increase the risk for developing hepatic steatohepatitis, leading to end-stage liver disease .
Obese patients demosntrate a 58–74% increased prevalence of NAFLD . NAFLD is present in 32% of premenopausal women compared with 58% of postmenopausal women; suggesting that circulating estrogen may be protective against NAFLD . Low estrogen level associated with menopause has been linked to body fat redistribution leading to visceral fat accumulation, which may influence the development and progression of NAFLD .
The majority of patients are asymptomatic; however, some might have hepatomegaly, general malaise, abdominal discomfort, vague right upper quadrant abdominal pain, nausea, and other nonspecific symptoms referred to the gastrointestinal tract . NAFLD development is associated with the presence of factors such as obesity and hyperlipidemia . Although serum aminotransferase level is mildly elevated, liver enzymes may be normal in up to 78% of patients with NAFLD .
To manage or even treat NAFLD, it has been suggested that lifestyle modification through diet and exercise is a highly effective therapy . Hypocaloric diet therapy has been reported to result in decreased total cholesterol (TC) , weight loss, reduced intra-abdominal fat, and improved high-density lipoprotein cholesterol (HDL-C) levels in obese women . Others reported weight loss and decreased BMI following 7 weeks of a low-caloric diet in patients with nonalcoholic hepatic steatosis without changes in HDL-C, low-density lipoprotein cholesterol (LDL-C), and triglycerides (TGs) . Kistler et al.  reported that vigorous, but not moderate-intensity exercise may be effective for treating NAFLD.
High-intensity interval training (HIIT) is characterized by brief, intermittent bursts of vigorous activity, interspersed by periods of rest or low-intensity exercise. HIIT can be used as an alternative to traditional endurance training. It is an effective exercise protocol for reducing fat of overweight patients  through increasing energy expenditure and increasing fatty acid oxidation .
Therefore, this study aimed to: (a) determine the effect of hypocaloric diet–HIIT intervention versus hypocaloric diet alone on anthropometric measurements, lipids, estradiol level, and liver size in obese postmenopausal women with hepatic steatosis; and (b) find out the factors predicting changes in lipids, estradiol level, as well as liver size in response to diet–HIIT intervention. We hypothesized that hypocaloric diet–HIIT intervention would improve anthropometric measurements, lipids, estradiol level, and liver size more than hypocaloric diet in postmenopausal women with hepatic steatosis. Also, changes in anthropometric measurements and lipids may be predictors for the change in estradiol level and liver size in response to diet–HIIT intervention.
| Patients and methods|| |
Sixty postmenopausal women were recruited by a specialist in internal medicine according to the following criteria: patient’s age ranged between 50 and 60 years and BMI more than 30 kg/m2. They experienced menopause for more than 3 years. All postmenopausal women demonstrated mild hepatomegaly (liver size >16–18 cm) . Ultrasonography was used to confirm the diagnosis of hepatic steatosis. Ultrasonographic findings included the presence of diffuse increases in echogenicity of liver parenchyma characterized by the absence of hyperechoic walls of portal vein radicals and absence of a proper interface between the diaphragm and liver .
Exclusion criteria for postmenopausal women included: hypothyroidism, ischemic heart disease, kidney disease, diabetes, secondary causes of liver disease including ethanol abuse, drugs promoting hepatic steatosis, various surgical procedures enhancing NAFLD, and those using hormone replacement therapy or antidiabetic medications.
Postmenopausal women were randomized to either the diet or diet–HIIT group using a computer-generated random numbers method. The diet group received a hypocaloric diet, whereas the diet–HIIT group received a hypocaloric diet and participated in a HIIT protocol equal to three times per week for 12 weeks.
Sample size calculation
A sample size before was calculated based on the changes in waist circumference and TGs . Sample size equal to 25 participants per group was computed to detect medium effect size differences of 0.74 and 0.73 for weight and TG, respectively, at a power equal to 80% and alpha level of 0.05.
All participants provided written informed consent before study participation. All procedures of this study were complied with the Ethical Standards of the Declaration of Helsinki.
| Design of the study|| |
This study was a randomized controlled trial.
A researcher blinded to the group assignment performed all anthropometric measurements. Weight and height were measured to calculate BMI by dividing weight (kg) by height (m2). Waist girth was measured from the narrowest point between the lower borders of the rib cage and the iliac crest at the end of the normal expiration.
Blood samples were collected from postmenopausal women at 9 a.m. following a 12-h fast. Blood samples were collected in tubes containing few milligram of K2EDTA. After centrifuging the samples, plasma was separated and stored in a freezer at −20°C. Stored samples were later analyzed for lipid profiles, including TC, TG, HDL-C, and LDL-C, which were estimated using the enzymatic method . Serum estradiol levels were assessed using the radioimmunoassay method .
Liver size assessment
The radiologist measured the liver size of all postmenopausal women using ultrasonography. He was blinded to the group assignments. He measured the right midclavicular plane as an indicator of liver size, which was suggested to be a valid and reliable method . Liver length greater than 16 cm was used as a criterion for identifying patients with hepatomegaly .
All participants followed a calorie-restricted diet that was moderately low in fat with a recommended macronutrient distribution of 55% carbohydrate, 15% protein, and 30% fat. Calorie prescriptions were calculated using the Harris–Benedict equation, which is a method used to estimate an individual’s basal metabolic rate (BMR). BMR=(10×weight in kg)+(6.25×height in cm)–(5×age in years)–161. Then, total energy intake was calculated by multiplying BMR and a factor of 1.53 . A dietitian blinded to a group assignment interviewed participants for individual counseling sessions at a special clinic. The dietitian reviewed the 3-day food diaries for each participant on a weekly basis to ensure that participants adhered to the restricted diet plans and also provided dietary recommendations during sessions .
High-intensity interval training intervention
Postmenopausal women randomized to the exercise group performed HIIT sessions consisting of treadmill walking. Each participant performed independent exercise sessions supervised by a physical therapist at a physical therapy clinic. During these sessions, participants performed a 5-min warm-up at an intensity corresponding to 65–75% of heart rate maximum (HRmax) before walking four intervals of 4-min length at 85–95% of HRmax. The HIIT intervals were interspersed by 3-min periods of walking at 65–75% of HRmax. Participants ended each session with a 3-min cool down period at 65–75% of HRmax, amounting to a total exercise time of 33 min. All women were trained at the lower-intensity limit for the first 2 weeks of the program before increasing the intensity levels toward the upper limit. The therapist adjusted the speed and inclination of the treadmill, as training progressed through the program intervention to ensure that postmenopausal women performed all training sessions at the desired HR. The total length of the HIIT intervention was 12 weeks, which included three sessions per week. The therapist encouraged all women to maintain their normal level of daily living activities, while not engaging in any outside exercise training programs during the 12-week HIIT intervention . Adherence to HIIT intervention was recorded by counting the number of sessions for each participant. The number of HIIT sessions for all participants ranged from 35 to 36 sessions.
Data was expressed as means±SD. Kolmogorov–Smirnov test was used to assess the normal distribution of data. Repeated measures multivariate analysis of variance was used to analyze within and between group differences of all variables in both groups. Pearson’s correlation coefficient test was used to measure correlations between the mean changes of dependent variables. In addition, multiple linear regression (stepwise method) was used to predict multiple correlated dependent variables. The statistical level of significance was set at P value less than 0.05. Data was analyzed using statistical package for the social sciences (version 16; SPSS Inc., Chicago, Illinois, USA).
| Results|| |
Sixty participants were randomized to either the diet or diet–HIIT group, but four women dropped from the exercise group because of personal reasons. Participants in the diet–HIIT group attended 34–36 sessions of HIIT training. Baseline characteristics of all postmenopausal women in the diet and exercise groups showed no significant difference between the groups ([Table 1]).
|Table 1 Baseline characteristics of postmenopausal women in diet and diet–high-intensity interval training groups|
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[Table 2] illustrates within group and between group comparisons for both groups. In the diet group, weight decreased from 102.57±7.98 to 92.67±7.04, BMI decreased from 39.51±3.53 to 35.70±3.19, waist girth decreased from 120.8±7.17 to 111.97±6.80, TC decreased from 199.87±29.59 to 181.70±30.33, TG decreased from 160.37±31.41 to 143.57±29.68, LDL-C decreased from 141.83±18.15 to 131.03±15.44, HDL-C increased from 40.2±6.27 to 41.13±6.70, estradiol level increased from 15.57±3.64 to 16.98±3.51, and liver size decreased from 17.61±0.81 to 16.34±0.87.
|Table 2 Repeated measures multivariate analysis of variance for all measured variables in diet and diet–high-intensity interval training groups|
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In the diet–HIIT group, weight decreased from 105.54±10.14 to 94.58±9.61, BMI decreased from 40.56±3.40 to 36.34±3.26, waist girth decreased from 120.77±11.23 to 107.31±10.17, TC decreased from 210.38±25.01 to 188.58±23.23, TG decreased from 151.27±24.88 to 121.73±36.82, LDL-C decreased from 139.61±24.14 to 129.50±21.78, HDL-C increased from 42.11±2.86 to 43.46±2.94, estradiol level increased from 14.33±4.28 to 20.92±2.25, and liver size decreased from 17.59±0.76 to 15.83±0.89. In both groups, changes from baseline to follow-up were significant (P<0.0001) for each of the above variables. Time-group interaction demonstrated that the diet–HIIT group had a greater decrease in waist girth (P<0.0001), TG (P=0.002), and liver size (P=0.005), as well as a greater increase in HDL-C (P=0.03) and estradiol level (P<0.0001) than the diet group.
[Table 3] shows correlations between mean changes of all dependent variables. Reduced weight showed a significant positive correlation with the changes in TG (r=0.59; P=0.001), HDL-C (r=0.58; P=0.001), estradiol level (r=0.55; P=0.003), and liver size (r=0.44; P=0.02). Change in TG showed a significant correlation with changes in waist girth (r=0.55; P=0.03) and HDL-C (r=0.41; P=0.02). Change in estradiol level demonstrated a significant positive correlation with changes in TG (r=0.55; P=0.002), HDL-C (r=0.58; P=0.001), and liver size (r=0.72; P=0.0002). Finally, the change in liver size showed a significant positive correlation with changes in TG (r=0.53; P=0.006) and HDL-C (r=0.63; P=0.001).
|Table 3 Pearson’s correlation between mean changes of all measured variables in the diet–high-intensity interval training group|
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[Table 4] represents the predicted models of the correlated dependent variables in diet–HIIT group. Results showed two models for predicting the change in estradiol and one model for predicting TG, HDL-C and liver size changes, which showed good and significant level of prediction. The change in estradiol level explained 33% of variability in HDL-C and 52% of variability in liver size. In addition, change in HDL-C or combined HDL-C and TG accounted for 33 and 45% of variability in estradiol level, respectively. Decreased weight accounted for 35% of variability in TG.
|Table 4 Linear regression analysis models of correlated variables in diet–high-intensity interval training group|
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| Discussion|| |
Menopause is associated with many changes , including reduced estradiol level that affect the development and progression of NAFLD . Lifestyle change by diet and exercise is the first line treatment for fatty liver. Therefore, this study aimed to investigate the effect of hypocaloric diet regime and hypocaloric diet–HIIT intervention on anthropometric measurements, lipids, estradiol level, and liver size in postmenopausal women with hepatic steatosis. The results demonstrated that both hypocaloric diet regime and hypocaloric diet–HIIT intervention were effective in improving anthropometric measurements, lipids, estradiol level, and liver size. However, hypocaloric diet–HIIT intervention produced a greater decrease in waist girth, TG, and liver size, as well as a greater increase in HDL-C and estradiol level than hypocaloric diet alone.
These data are consistent with previous work, suggesting that a calorie-restricted diet (caloric deficit of 600–800 kcal/day) for 3 months contributed to improved lipid profiles with a significant decrease in TC , reduced weight, and improved intra-abdominal fat, as well as HDL-C in obese women . By contrast, others have reported reduced weight and BMI without significant changes in HDL-C, LDL-C, and TG following 7 weeks of low-caloric dieting in patients with nonalcoholic hepatic steatosis . The different outcomes may be attributable to the markedly different interventions used between the two studies. The findings are supported by Petersen et al.  who demonstrated that moderate weight loss by calorie restriction could improve lipid metabolism and glucose metabolism in the liver, with reduction of hepatic fat accumulation.
Previous studies showed small decrease in BMI after HIIT training ,. In addition, numerous studies have reported improvements in waist girth ,, following participation in HIIT intervention, which is consistent with the present observations. Waist circumference has stronger association with cardiovascular risk factors than BMI . Hence, improved waist circumference indicates that the diet–HIIT intervention is more effective to guard against cardiovascular risk diseases in postmenopausal women than diet alone.
In addition, Racil et al.  supported the findings of this study. They showed significant decrease in TG, TC, and LDL-C, and a significant increase in HDL-C after HIIT in obese adolescents females. The greater improvement in waist girth and TG in response to diet–HIIT intervention is attributed to increased fat loss as a result of increased capacity of the skeletal muscle to perform fatty acid oxidation . Increased fat loss can explain the finding that weight loss is an independent significant predictor for the change in TG. Adipose tissue lipolysis of TGs to fatty acids is considered to be the mechanism for removing TGs postexercise ,. This can explain that high-intensity exercise requires glucose catabolism, and in consequence glucose metabolism is turned away to restore muscle glycogen. This muscle glycogen resynthesis is of high metabolic priority inducing postexercise lipid combustion, in which the muscle triacylglycerols are important providers of fuel for postexercise muscle metabolism and recovery processes .
The increased HDL-C in the present study is consistent with Roberts et al.  who demonstrated improvements in HDL-C function after only 3 weeks of training and dietary intervention in patients at risk for metabolic syndrome. In addition, Tjønna et al.  reported significant improvements in HDL-C concentration along with improvements in body composition in the HIIT group after 3 months of training. Moreover, Ciolac et al.  showed that exercise training increases HDL-C, as well as reduces TG and LDL-C in normotensive women at high risk for hypertension.
Increased HDL-C could be attributed to increased lipoprotein lipase enzyme activity in response to exercise. Lipoprotein lipase not only plays a role in the breakdown of TGs, but also is directly associated with HDL-C concentration, as it is involved in the maturation of HDL-C molecules by adding additional apoA-1 subunits to HDL-C . Hence we found positive significant correlation between HDL-C and TG.
Increase in estradiol level in respose to the diet–HIIT intevention is consistent with previous studies that reported the same finding following endurance ,, and resistance exercises . However, others reported opposite findings to the present observations ,,. The contradictory results may be attributed to the differences in intensity and duration of the prescribed exercise, which may affect the response of estradiol to training . Increased metabolic clearance rates that occur with exercise may explain the previous increase ; however, this mechanism was not be investigated in this study.
The change in estradiol level showed significant positive correlations with changes in weight, TG, and HDL-C. However, when they enter the linear regression model, only changes in TG and HDL-C are significant predictors for the change in the estradiol level, independent of reduced weight.
In addition to this, the change in estradiol level is a significant predictor for the change in HDL-C. The previous findings are in consistence with Walsh et al.  who reported that serum estradiol level produced by oral estradiol treatment was positively correlated with the increase in HDL-C. Response of estradiol level  and lipid contribution to energetic metabolism is dependent on exercise intensity and duration , hence high-intensity exercise is preferable for postmenopausal women with fatty liver.
Improved liver size found in response to hypocaloric diet–HIIT intervention showed significant positive correlations with changes in the weight, TG, HDL-C, and estradiol level. However, only the change in estradiol level is the strong predictor for improved liver size independent of weight loss. This finding is supported by the hypothesis regarding the role that estradiol plays in reducing the severity and progression of NAFLD. The mechanism that could explain decreased liver size is that improved estradiol level may reduce fat deposition in the liver through disrupting insulin effects on promoting fat storage in the liver, as well as maintaining liver TG export . This finding suggests that adding a treatment focusing on increasing estradiol level to HIIT intervention may enhance the treatment of fatty liver. However, this suggestion needs further investigations.
Further studies are needed to investigate the effects of HIIT in postmenopausal women with more advanced stages of liver disease. In addition, future studies are needed to elucidate underlying physiologic reasons for responses of liver enzymes to HIIT in obese women with hepatic steatosis or steatohepatitis.
In conclusion, these data suggest that weight loss by HIIT and diet intervention improved lipids, liver size, and estradiol level in obese postmenopausal women with hepatic steatosis. The change in estradiol level is a significant predictor for the change in HDL-C and liver size. Therefore, the improved estradiol level independent of weight loss is an important indicator for improving liver size in obese women with fatty liver.
Financial support and sponsorship
Nil.Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4]