human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: OBJECTIVE Nonalcoholic fatty liver disease ( NAFLD ) and its association with insulin resistance are increasingly recognized as major health burdens . The main objectives of this study were to assess the relation between liver lipid content and serum lipids , markers of liver function and inflammation in healthy overweight subjects , and to determine whether caloric restriction ( CR ) ( which improves insulin resistance ) reduces liver lipids in association with these same measures . METHODS AND PROCEDURES Forty-six white and black overweight men and women ( BMI = 24.7 - 31.3 kg/m(2 ) ) were r and omized to " control ( CO ) " = 100 % energy requirements ; " CR " = 25 % ; " caloric restriction and increased structured exercise (CR+EX)"= 12.5 % CR + 12.5 % increase in energy expenditure through exercise ; or " low-calorie diet ( LCD ) " = 15 % weight loss by liquid diet followed by weight-maintenance , for 6 months . Liver lipid content was assessed by magnetic resonance spectroscopy ( MRS ) and computed tomography ( CT ) . Lipid concentrations , markers of liver function ( alanine aminotransferase ( ALT ) , alkaline phosphatase ( ALK ) ) , and whole-body inflammation ( tumor necrosis factor-alpha ( TNF-alpha ) , interleukin-6 ( IL-6 ) , high-sensitivity C-reactive protein ( hsCRP ) ) were measured in fasting blood . RESULTS At baseline , increased liver lipid content ( by MRS ) correlated ( P < 0.05 ) with elevated fasting triglyceride ( r = 0.52 ) , ALT ( r = 0.42 ) , and hsCRP ( r = 0.33 ) concentrations after adjusting for sex , race , and alcohol consumption . With CR , liver lipid content was significantly lowered by CR , CR+EX , and LCD ( detected by MRS only ) . The reduction in liver lipid content , however , was not significantly correlated with the reduction in triglycerides ( r = 0.26 ; P = 0.11 ) or with the changes in ALT , high-density lipoprotein (HDL)-cholesterol , or markers of whole-body inflammation . DISCUSSION CR may be beneficial for reducing liver lipid and lowering triglycerides in overweight subjects without known NAFLD Exercise training is commonly prescribed for treatment of nonalcoholic fatty liver disease ( NAFLD ) . We sought to determine whether exercise training prevents the development of NAFLD in Otsuka Long-Evans Tokushima Fatty ( OLETF ) rats and to eluci date the molecular mechanisms underlying the effects of exercise on hepatic steatosis . Four-week-old OLETF rats were r and omly assigned to either a sedentary control group ( Sed ) or a group given access to voluntary running wheels for 16 wk ( Ex ) . Wheels were locked 2 days before euthanasia in the Ex animals , and both groups were euthanized at 20 wk old . Voluntary wheel running attenuated weight gain and reduced serum glucose , insulin , free fatty acids , and triglycerides in Ex animals compared with Sed ( P < 0.001 ) . Ex animals exhibited significantly reduced hepatic triglyceride levels and displayed fewer lipid droplets ( Oil Red O staining ) and reduced lipid droplet size compared with Sed . Wheel running increased by threefold the percent of palmitate oxidized completely to CO(2 ) in the Ex animals but did not alter AMP-activated protein kinase-alpha ( AMPKalpha ) or AMPK phosphorylation status . However , fatty acid synthase and acetyl-coenzyme A carboxylase ( ACC ) content were significantly reduced ( approximately 70 and approximately 35 % , respectively ) , and ACC phosphorylation and cytochrome c content were significantly elevated ( approximately 35 and approximately 30 % , respectively ) in the Ex animals . These results unequivocally demonstrate that daily physical activity attenuates hepatic steatosis and NAFLD in an obese rodent model and suggest that this effect is likely mediated , in part , through enhancement of hepatic fatty acid oxidation and reductions in key protein intermediates of fatty acid synthesis Despite the increasing prevalence of nonalcoholic fatty liver disease ( NAFLD ) , the criteria used to diagnose the disorder remain poorly defined . Localized proton magnetic resonance spectroscopy ( MRS ) accurately measures hepatic triglyceride content ( HTGC ) but has been used only in small research studies . Here , MRS was used to analyze the distribution of HTGC in 2,349 participants from the Dallas Heart Study ( DHS ) . The reproducibility of the procedure was vali date d by showing that duplicate HTGC measurements were high correlated ( r = 0.99 , P < 0.001 ) and that the coefficient of variation between measurements was low ( 8.5 % ) . Intake of a high-fat meal did not significantly affect the measurements , and values were similar when measurements were made from the right and left hepatic lobes . To determine the " upper limit of normal " for HTGC , the distribution of HTGC was examined in the 345 subjects from the DHS who had no identifiable risk factors for hepatic steatosis ( nonobese , nondiabetic subjects with minimal alcohol consumption , normal liver function tests , and no known liver disease ) . The 95th percentile of HTGC in these subjects was 5.56 % , which corresponds to a hepatic triglyceride level of 55.6 mg/g . With this value as a cutoff , the prevalence of hepatic steatosis in Dallas County was estimated to be 33.6 % . Thus MRS provides a sensitive , quantitative , noninvasive method to measure HTGC and , when applied to a large urban US population , revealed a strikingly high prevalence of hepatic steatosis Background : To investigate the effects of varied therapeutic lifestyle programs on patients with ultrasound‐diagnosed nonalcoholic fatty liver disease ( NAFLD ) . Methods : A prospect i ve , case‐controlled study was conducted . A total of 54 subjects with NAFLD were subdivided into 3 groups : ( 1 ) diet plus exercise group ( DPE group , n = 16 ) ; ( 2 ) exercise group ( E group , n = 23 ) ; and ( 3 ) control group ( C group , n = 15 ) . The DPE group received a low‐calorie balanced diet and regular high‐intensity stationary bicycle exercise program for 10 weeks , while the E group received the same exercise protocol as the DPE group but without any changes in diet . Anthropometric indices , biochemical data , physical fitness data and liver ultrasound findings were recorded . A generalized estimating equation method was used to determine the differences among groups . Results : Compared with the C group , the DPE group demonstrated significant improvements in anthropometric indices , total cholesterol , insulin sensitivity , liver biochemistry , ultrasound finding and physical fitness , while the E group showed significant improvements in anthropometric indices , insulin sensitivity status , ultrasound finding and physical fitness but not liver biochemistry . Compared with the E group , the DPE group showed greater reduction in anthropometric indices ( body mass index , body weight , abdominal circumference , hip circumference ) , total cholesterol , alanine aminotransferase , and γ‐glutamyltransferase . Conclusion : Our data suggest that both 10‐week diet‐plus‐exercise and exercise‐only therapeutic lifestyle programs are effective for improving anthropometric indices , insulin sensitivity , ultrasound findings and physical fitness in ultrasound‐diagnosed NAFLD patients . However , the range of improvement in patients on the diet‐plus‐exercise program is more obvious than that in patients on the exercise‐only program . Moreover , the diet‐plus‐exercise program result ed in significant improvement in liver biochemistry , but the exercise‐only program did not . In summary , diet plus exercise is more efficacious than exercise alone in the lifestyle modification treatment of NAFLD Skeletal muscle insulin resistance has been implicated in the pathogenesis of nonalcoholic fatty liver disease ( NAFLD ) and atherogenic dyslipidemia associated with the metabolic syndrome by altering the distribution pattern of postpr and ial energy storage . We conducted a study to examine this hypothesis by reversing muscle insulin resistance with a single bout of exercise and measuring hepatic de novo lipogenesis and hepatic triglyceride synthesis after a carbohydrate-rich meal . We studied 12 healthy , young , lean , insulin resistant individuals in an interventional , r and omized cross-over trial . The response to the ingestion of a carbohydrate-rich meal was studied at rest and after one 45-min bout of exercise on an elliptical trainer .  Hepatic de novo lipogenesis was assessed by using 2H2O , and changes in glycogen and fat content in liver and muscle were measured by 13C and 1H magnetic resonance spectroscopy , respectively . Exercise result ed in a greater than threefold increase in postpr and ial net muscle glycogen synthesis ( P < 0.001 ) , reflecting improved muscle insulin responsiveness , and a ≈40 % reduction ( P < 0.05 ) in net hepatic triglyceride synthesis . These changes in whole body energy storage were accompanied by a ≈30 % decrease in hepatic de novo lipogenesis ( P < 0.01 ) and were independent of changes in fasting or postpr and ial plasma glucose and insulin concentrations . These data demonstrate that skeletal muscle insulin resistance is an early therapeutic target for the treatment and prevention of atherogenic dyslipidemia and NAFLD in young insulin resistant individuals who are prone to develop the metabolic syndrome and type 2 diabetes BACKGROUND Type 2 diabetes mellitus is increasingly common , primarily because of increases in the prevalence of a sedentary lifestyle and obesity . Whether type 2 diabetes can be prevented by interventions that affect the lifestyles of subjects at high risk for the disease is not known . METHODS We r and omly assigned 522 middle-aged , overweight subjects ( 172 men and 350 women ; mean age , 55 years ; mean body-mass index [ weight in kilograms divided by the square of the height in meters ] , 31 ) with impaired glucose tolerance to either the intervention group or the control group . Each subject in the intervention group received individualized counseling aim ed at reducing weight , total intake of fat , and intake of saturated fat and increasing intake of fiber and physical activity . An oral glucose-tolerance test was performed annually ; the diagnosis of diabetes was confirmed by a second test . The mean duration of follow-up was 3.2 years . RESULTS The mean ( + /-SD ) amount of weight lost between base line and the end of year 1 was 4.2+/-5.1 kg in the intervention group and 0.8+/-3.7 kg in the control group ; the net loss by the end of year 2 was 3.5+/-5.5 kg in the intervention group and 0.8+/-4.4 kg in the control group ( P<0.001 for both comparisons between the groups ) . The cumulative incidence of diabetes after four years was 11 percent ( 95 percent confidence interval , 6 to 15 percent ) in the intervention group and 23 percent ( 95 percent confidence interval , 17 to 29 percent ) in the control group . During the trial , the risk of diabetes was reduced by 58 percent ( P<0.001 ) in the intervention group . The reduction in the incidence of diabetes was directly associated with changes in lifestyle . CONCLUSIONS Type 2 diabetes can be prevented by changes in the lifestyles of high-risk subjects The rise in obesity-related morbidity in children and adolescents requires urgent prevention and treatment strategies . Currently , only limited data are available on the effects of exercise programs on insulin resistance , and visceral , hepatic , and intramyocellular fat accumulation . We hypothesized that a 12-week controlled aerobic exercise program without weight loss reduces visceral , hepatic , and intramyocellular fat content and decreases insulin resistance in sedentary Hispanic adolescents . Twenty-nine postpubertal ( Tanner stage IV and V ) , Hispanic adolescents , 15 obese ( 7 boys , 8 girls ; 15.6 + /- 0.4 years ; 33.7 + /- 1.1 kg/m(2 ) ; 38.3 + /- 1.5 % body fat ) and 14 lean ( 10 boys , 4 girls ; 15.1 + /- 0.3 years ; 20.6 + /- 0.8 kg/m(2 ) ; 18.9 + /- 1.5 % body fat ) , completed a 12-week aerobic exercise program ( 4 x 30 min/week at > or = 70 % of peak oxygen consumption ( VO(2)peak ) ) . Measurements of cardiovascular fitness , visceral , hepatic , and intramyocellular fat content ( magnetic resonance imaging (MRI)/magnetic resonance spectroscopy ( MRS ) ) , and insulin resistance were obtained at baseline and postexercise . In both groups , fitness increased ( obese : 13 + /- 2 % , lean : 16 + /- 4 % ; both P < 0.01 ) . In obese participants , intramyocellular fat remained unchanged , whereas hepatic fat content decreased from 8.9 + /- 3.2 to 5.6 + /- 1.8 % ; P < 0.05 and vis 
    Output:
    
agent
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: OBJECTIVE Nonalcoholic fatty liver disease ( NAFLD ) and its association with insulin resistance are increasingly recognized as major health burdens . The main objectives of this study were to assess the relation between liver lipid content and serum lipids , markers of liver function and inflammation in healthy overweight subjects , and to determine whether caloric restriction ( CR ) ( which improves insulin resistance ) reduces liver lipids in association with these same measures . METHODS AND PROCEDURES Forty-six white and black overweight men and women ( BMI = 24.7 - 31.3 kg/m(2 ) ) were r and omized to " control ( CO ) " = 100 % energy requirements ; " CR " = 25 % ; " caloric restriction and increased structured exercise (CR+EX)"= 12.5 % CR + 12.5 % increase in energy expenditure through exercise ; or " low-calorie diet ( LCD ) " = 15 % weight loss by liquid diet followed by weight-maintenance , for 6 months . Liver lipid content was assessed by magnetic resonance spectroscopy ( MRS ) and computed tomography ( CT ) . Lipid concentrations , markers of liver function ( alanine aminotransferase ( ALT ) , alkaline phosphatase ( ALK ) ) , and whole-body inflammation ( tumor necrosis factor-alpha ( TNF-alpha ) , interleukin-6 ( IL-6 ) , high-sensitivity C-reactive protein ( hsCRP ) ) were measured in fasting blood . RESULTS At baseline , increased liver lipid content ( by MRS ) correlated ( P < 0.05 ) with elevated fasting triglyceride ( r = 0.52 ) , ALT ( r = 0.42 ) , and hsCRP ( r = 0.33 ) concentrations after adjusting for sex , race , and alcohol consumption . With CR , liver lipid content was significantly lowered by CR , CR+EX , and LCD ( detected by MRS only ) . The reduction in liver lipid content , however , was not significantly correlated with the reduction in triglycerides ( r = 0.26 ; P = 0.11 ) or with the changes in ALT , high-density lipoprotein (HDL)-cholesterol , or markers of whole-body inflammation . DISCUSSION CR may be beneficial for reducing liver lipid and lowering triglycerides in overweight subjects without known NAFLD Exercise training is commonly prescribed for treatment of nonalcoholic fatty liver disease ( NAFLD ) . We sought to determine whether exercise training prevents the development of NAFLD in Otsuka Long-Evans Tokushima Fatty ( OLETF ) rats and to eluci date the molecular mechanisms underlying the effects of exercise on hepatic steatosis . Four-week-old OLETF rats were r and omly assigned to either a sedentary control group ( Sed ) or a group given access to voluntary running wheels for 16 wk ( Ex ) . Wheels were locked 2 days before euthanasia in the Ex animals , and both groups were euthanized at 20 wk old . Voluntary wheel running attenuated weight gain and reduced serum glucose , insulin , free fatty acids , and triglycerides in Ex animals compared with Sed ( P < 0.001 ) . Ex animals exhibited significantly reduced hepatic triglyceride levels and displayed fewer lipid droplets ( Oil Red O staining ) and reduced lipid droplet size compared with Sed . Wheel running increased by threefold the percent of palmitate oxidized completely to CO(2 ) in the Ex animals but did not alter AMP-activated protein kinase-alpha ( AMPKalpha ) or AMPK phosphorylation status . However , fatty acid synthase and acetyl-coenzyme A carboxylase ( ACC ) content were significantly reduced ( approximately 70 and approximately 35 % , respectively ) , and ACC phosphorylation and cytochrome c content were significantly elevated ( approximately 35 and approximately 30 % , respectively ) in the Ex animals . These results unequivocally demonstrate that daily physical activity attenuates hepatic steatosis and NAFLD in an obese rodent model and suggest that this effect is likely mediated , in part , through enhancement of hepatic fatty acid oxidation and reductions in key protein intermediates of fatty acid synthesis Despite the increasing prevalence of nonalcoholic fatty liver disease ( NAFLD ) , the criteria used to diagnose the disorder remain poorly defined . Localized proton magnetic resonance spectroscopy ( MRS ) accurately measures hepatic triglyceride content ( HTGC ) but has been used only in small research studies . Here , MRS was used to analyze the distribution of HTGC in 2,349 participants from the Dallas Heart Study ( DHS ) . The reproducibility of the procedure was vali date d by showing that duplicate HTGC measurements were high correlated ( r = 0.99 , P < 0.001 ) and that the coefficient of variation between measurements was low ( 8.5 % ) . Intake of a high-fat meal did not significantly affect the measurements , and values were similar when measurements were made from the right and left hepatic lobes . To determine the " upper limit of normal " for HTGC , the distribution of HTGC was examined in the 345 subjects from the DHS who had no identifiable risk factors for hepatic steatosis ( nonobese , nondiabetic subjects with minimal alcohol consumption , normal liver function tests , and no known liver disease ) . The 95th percentile of HTGC in these subjects was 5.56 % , which corresponds to a hepatic triglyceride level of 55.6 mg/g . With this value as a cutoff , the prevalence of hepatic steatosis in Dallas County was estimated to be 33.6 % . Thus MRS provides a sensitive , quantitative , noninvasive method to measure HTGC and , when applied to a large urban US population , revealed a strikingly high prevalence of hepatic steatosis Background : To investigate the effects of varied therapeutic lifestyle programs on patients with ultrasound‐diagnosed nonalcoholic fatty liver disease ( NAFLD ) . Methods : A prospect i ve , case‐controlled study was conducted . A total of 54 subjects with NAFLD were subdivided into 3 groups : ( 1 ) diet plus exercise group ( DPE group , n = 16 ) ; ( 2 ) exercise group ( E group , n = 23 ) ; and ( 3 ) control group ( C group , n = 15 ) . The DPE group received a low‐calorie balanced diet and regular high‐intensity stationary bicycle exercise program for 10 weeks , while the E group received the same exercise protocol as the DPE group but without any changes in diet . Anthropometric indices , biochemical data , physical fitness data and liver ultrasound findings were recorded . A generalized estimating equation method was used to determine the differences among groups . Results : Compared with the C group , the DPE group demonstrated significant improvements in anthropometric indices , total cholesterol , insulin sensitivity , liver biochemistry , ultrasound finding and physical fitness , while the E group showed significant improvements in anthropometric indices , insulin sensitivity status , ultrasound finding and physical fitness but not liver biochemistry . Compared with the E group , the DPE group showed greater reduction in anthropometric indices ( body mass index , body weight , abdominal circumference , hip circumference ) , total cholesterol , alanine aminotransferase , and γ‐glutamyltransferase . Conclusion : Our data suggest that both 10‐week diet‐plus‐exercise and exercise‐only therapeutic lifestyle programs are effective for improving anthropometric indices , insulin sensitivity , ultrasound findings and physical fitness in ultrasound‐diagnosed NAFLD patients . However , the range of improvement in patients on the diet‐plus‐exercise program is more obvious than that in patients on the exercise‐only program . Moreover , the diet‐plus‐exercise program result ed in significant improvement in liver biochemistry , but the exercise‐only program did not . In summary , diet plus exercise is more efficacious than exercise alone in the lifestyle modification treatment of NAFLD Skeletal muscle insulin resistance has been implicated in the pathogenesis of nonalcoholic fatty liver disease ( NAFLD ) and atherogenic dyslipidemia associated with the metabolic syndrome by altering the distribution pattern of postpr and ial energy storage . We conducted a study to examine this hypothesis by reversing muscle insulin resistance with a single bout of exercise and measuring hepatic de novo lipogenesis and hepatic triglyceride synthesis after a carbohydrate-rich meal . We studied 12 healthy , young , lean , insulin resistant individuals in an interventional , r and omized cross-over trial . The response to the ingestion of a carbohydrate-rich meal was studied at rest and after one 45-min bout of exercise on an elliptical trainer .  Hepatic de novo lipogenesis was assessed by using 2H2O , and changes in glycogen and fat content in liver and muscle were measured by 13C and 1H magnetic resonance spectroscopy , respectively . Exercise result ed in a greater than threefold increase in postpr and ial net muscle glycogen synthesis ( P < 0.001 ) , reflecting improved muscle insulin responsiveness , and a ≈40 % reduction ( P < 0.05 ) in net hepatic triglyceride synthesis . These changes in whole body energy storage were accompanied by a ≈30 % decrease in hepatic de novo lipogenesis ( P < 0.01 ) and were independent of changes in fasting or postpr and ial plasma glucose and insulin concentrations . These data demonstrate that skeletal muscle insulin resistance is an early therapeutic target for the treatment and prevention of atherogenic dyslipidemia and NAFLD in young insulin resistant individuals who are prone to develop the metabolic syndrome and type 2 diabetes BACKGROUND Type 2 diabetes mellitus is increasingly common , primarily because of increases in the prevalence of a sedentary lifestyle and obesity . Whether type 2 diabetes can be prevented by interventions that affect the lifestyles of subjects at high risk for the disease is not known . METHODS We r and omly assigned 522 middle-aged , overweight subjects ( 172 men and 350 women ; mean age , 55 years ; mean body-mass index [ weight in kilograms divided by the square of the height in meters ] , 31 ) with impaired glucose tolerance to either the intervention group or the control group . Each subject in the intervention group received individualized counseling aim ed at reducing weight , total intake of fat , and intake of saturated fat and increasing intake of fiber and physical activity . An oral glucose-tolerance test was performed annually ; the diagnosis of diabetes was confirmed by a second test . The mean duration of follow-up was 3.2 years . RESULTS The mean ( + /-SD ) amount of weight lost between base line and the end of year 1 was 4.2+/-5.1 kg in the intervention group and 0.8+/-3.7 kg in the control group ; the net loss by the end of year 2 was 3.5+/-5.5 kg in the intervention group and 0.8+/-4.4 kg in the control group ( P<0.001 for both comparisons between the groups ) . The cumulative incidence of diabetes after four years was 11 percent ( 95 percent confidence interval , 6 to 15 percent ) in the intervention group and 23 percent ( 95 percent confidence interval , 17 to 29 percent ) in the control group . During the trial , the risk of diabetes was reduced by 58 percent ( P<0.001 ) in the intervention group . The reduction in the incidence of diabetes was directly associated with changes in lifestyle . CONCLUSIONS Type 2 diabetes can be prevented by changes in the lifestyles of high-risk subjects The rise in obesity-related morbidity in children and adolescents requires urgent prevention and treatment strategies . Currently , only limited data are available on the effects of exercise programs on insulin resistance , and visceral , hepatic , and intramyocellular fat accumulation . We hypothesized that a 12-week controlled aerobic exercise program without weight loss reduces visceral , hepatic , and intramyocellular fat content and decreases insulin resistance in sedentary Hispanic adolescents . Twenty-nine postpubertal ( Tanner stage IV and V ) , Hispanic adolescents , 15 obese ( 7 boys , 8 girls ; 15.6 + /- 0.4 years ; 33.7 + /- 1.1 kg/m(2 ) ; 38.3 + /- 1.5 % body fat ) and 14 lean ( 10 boys , 4 girls ; 15.1 + /- 0.3 years ; 20.6 + /- 0.8 kg/m(2 ) ; 18.9 + /- 1.5 % body fat ) , completed a 12-week aerobic exercise program ( 4 x 30 min/week at > or = 70 % of peak oxygen consumption ( VO(2)peak ) ) . Measurements of cardiovascular fitness , visceral , hepatic , and intramyocellular fat content ( magnetic resonance imaging (MRI)/magnetic resonance spectroscopy ( MRS ) ) , and insulin resistance were obtained at baseline and postexercise . In both groups , fitness increased ( obese : 13 + /- 2 % , lean : 16 + /- 4 % ; both P < 0.01 ) . In obese participants , intramyocellular fat remained unchanged , whereas hepatic fat content decreased from 8.9 + /- 3.2 to 5.6 + /- 1.8 % ; P < 0.05 and vis 
    Output:
    