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 visceral fat content from 54.7 +/- 6.0 to 49.6 +/- 5.5 cm(2); P<0.05. Insulin resistance decreased indicated by decreased fasting insulin (21.8 +/- 2.7 to 18.2 +/- 2.4 microU/ml; P<0.01) and homeostasis model assessment of insulin resistance (HOMA(IR)) (4.9 +/- 0.7 to 4.1 +/- 0.6; P<0.01). The decrease in visceral fat correlated with the decrease in fasting insulin (R(2) = 0.40; P<0.05). No significant changes were observed in any parameter in lean participants except a small increase in lean body mass (LBM). Thus, a controlled aerobic exercise program, without weight loss, reduced hepatic and visceral fat accumulation, and decreased insulin resistance in obese adolescents.

OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) is a spectrum of liver disease characterised by accumulation of large-droplet fat in hepatocytes with possible progression to inflammation and fibrosis. Breastfeeding has benefits for child health, both during infancy and later in life, reducing the risk of manifestations of the metabolic syndrome. Here we investigated the association between early type of feeding (breastfed versus formula-fed and duration of breastfeeding) and later NAFLD development.

STUDY DESIGN: We investigated 191 young Caucasian children (3-18 years old) with NAFLD consecutively enrolled between January 2003 and September 2007 in our centre. 48% of these children (n = 91) had been breastfed for a median (interquartile range) time of 8 (7) months.

RESULTS: After correction for age, waist circumference, gestational age and neonatal weight, the odds of non-alcoholic steatohepatitis (NASH) (OR 0.04, 95% CI 0.01 to 0.10) and fibrosis (OR 0.32, 95% CI 0.16 to 0.65) were lower in breastfed versus not breastfed infants. Moreover, the odds of NASH (OR 0.70, exact 95% CI 0.001 to 0.87) and fibrosis (OR 0.86, exact 95% CI 0.75 to 0.98) decreased for every month of breastfeeding.

CONCLUSIONS: This observational study suggests that earlier feeding habits might affect the clinical expression of NASH from 3 to 18 years later, with an apparent drug-like preventive effect of breastfeeding.

Non-alcoholic steatosis (non-alcoholic fatty liver disease [NAFLD]), now considered a metabolic pathway to advanced liver disease, cirrhosis and hepatocellular carcinoma, can also be explained by physical inactivity and increased dietary fat intake. No established treatment exists for this potentially serious disorder. The authors present the case of a 29-year-old man with NALFD who followed a restricted diet and practiced aerobic exercise for 16 weeks. Outcome after a combination therapy of aerobic exercise and diet was good, suggesting that treatment with a restricted diet and physical exercise can improve blood biochemical values in patients with NAFLD. Moderate-intensity aerobic exercise may help to normalize liver enzyme values and the quality of life of patients with fatty liver diseases.

OBJECTIVE:To analyze the effect of an intervention with a Mediterranean diet supplemented with either extra virgin olive oil or nuts, on the fatty liver index (FLI), compared to a low-fat control diet.

METHODS:Participants of the PREDIMED-Malaga trial, free from cardiovascular disease at baseline, but with a high risk to develop it, were included in this study. Anthropometric measurements were assessed and blood samples were taken to calculate participants' FLI at study baseline and after one, 3, 5 and 6 years. Mixed linear models were used to explore the fixed effects of the 3 intervention groups on the FLI as well as their interaction with time.

RESULTS:A total of 276 participants were included in the study. Average participant age was 67 years, with 66% of participants being women. The baseline prevalence of NAFL was 57%. The change in the FLI of the control group increased significantly over time (1.13±0.41; P=.006). In the MedDiet+EVOO group, the time trend of the change in the FLI was similar to that of the control group, although it was seen to be lower (-3.90±1.9; P=.038). In the MedDiet+Nuts group, the trend was significantly lower than that of the control group (-1.63±0.62; P=.009). In the MedDiet+Nuts group, the trend of changes in participants' BMI was 0.100 points lower per year compared to the control group (P=.004). In the control group, the change in waist circumference increased significantly over time (0.61±0.16cm/year; P<.001) in contrast to the MedDiet+EVOO group, in which this variable remained stable (-0.51±0.22; P=.019).

CONCLUSIONS:A dietary intervention consisting of a Mediterranean diet could delay or slow down the natural progression of NAFL, thus, being beneficial for its prevention and treatment. However, further studies supporting these conclusions have yet to be carried out.

OBJECTIVE: This study compared the effects of casein and whey protein as the source of dietary protein on the activity of lipogenic enzymes and mRNA levels in the liver and skeletal muscle of exercise-trained rats.

METHODS: Twenty-eight male Sprague-Dawley rats were randomly assigned to one of four groups (n = 7/group). Rats were assigned to sedentary or exercise-trained groups and were fed the casein or whey protein diet. Rats in the exercise groups were trained for 2 wk using a swimming exercise for 120 min/d and 6 d/wk.

RESULTS: A significant decrease in the activity of the hepatic lipogenic enzymes, glucose-6-phosphate dehydrogenase, malic enzyme, adenosine triphosphate citrate lyase, acetyl-coenzyme A carboxylase, and fatty acid synthase (FASN) was observed in rats fed whey protein compared with animals fed casein. Compared with the casein diet, the whey protein diet also lowered mRNA expression of these enzymes, except for FASN. In contrast to the findings in liver, whey protein, as compared with casein, increased skeletal muscle FASN activity and mRNA. Further, exercise training resulted in increased skeletal muscle glucose-6-phosphate dehydrogenase and FASN activity and adenosine triphosphate citrate lyase, acetyl-coenzyme A carboxylase-1, and FASN mRNA expression.

CONCLUSIONS: Exercise training or whey protein may play an important role in suppressing hepatic fatty acid synthesis, thereby decreasing accumulation of body fat and stimulating the skeletal muscle to increase energy substrate as fat during prolonged exercise.

Background and Aims. This study examined if exercise and omega-3 fatty acid (n3PUFA) supplementation is an effective treatment for hepatic steatosis in obese, hyperphagic Otsuka Long-Evans Tokushima Fatty (OLETF) rats.

Methods. Male OLETF rats were divided into 4 groups (n = 8/group): (1) remained sedentary (SED), (2) access to running wheels; (EX) (3) a diet supplemented with 3% of energy from fish oil (n3PUFA-SED); and (4) n3PUFA supplementation plus EX (n3PUFA+EX). The 8 week treatments began at 13 weeks, when hepatic steatosis is present in OLETF-SED rats.

Results. EX alone lowered hepatic triglyceride (TAG) while, in contrast, n3PUFAs failed to lower hepatic TAG and blunted the ability of EX to decrease hepatic TAG levels in n3PUFAs+EX. Insulin sensitivity was improved in EX animals, to a lesser extent in n3PUFA+EX rats, and did not differ between n3PUFA-SED and SED rats. Only the EX group displayed higher complete hepatic fatty acid oxidation (FAO) to CO(2) and carnitine palmitoyl transferase-1 activity. EX also lowered hepatic fatty acid synthase protein while both EX and n3PUFA+EX decreased stearoyl CoA desaturase-1 protein.

Conclusions. Exercise lowers hepatic steatosis through increased complete hepatic FAO, insulin sensitivity, and reduced expression of de novo fatty acid synthesis proteins while n3PUFAs had no effect.

The clinical implications of non-alcoholic fatty liver diseases (NAFLD) derive from their potential to progress to fibrosis and cirrhosis. Inappropriate dietary fat intake, excessive intake of soft drinks, insulin resistance and increased oxidative stress results in increased free fatty acid delivery to the liver and increased hepatic triglyceride (TG) accumulation. An olive oil-rich diet decreases accumulation of TGs in the liver, improves postprandial TGs, glucose and glucagon-like peptide-1 responses in insulin-resistant subjects, and upregulates glucose transporter-2 expression in the liver. The principal mechanisms include: decreased nuclear factor-kappaB activation, decreased low-density lipoprotein oxidation, and improved insulin resistance by reduced production of inflammatory cytokines (tumor necrosis factor, interleukin-6) and improvement of jun N-terminal kinase-mediated phosphorylation of insulin receptor substrate-1. The beneficial effect of the Mediterranean diet is derived from monounsaturated fatty acids, mainly from olive oil. In this review, we describe the dietary sources of the monounsaturated fatty acids, the composition of olive oil, dietary fats and their relationship to insulin resistance and postprandial lipid and glucose responses in non-alcoholic steatohepatitis, clinical and experimental studies that assess the relationship between olive oil and NAFLD, and the mechanism by which olive oil ameliorates fatty liver, and we discuss future perspectives.

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 postprandial 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, randomized 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 (2)H(2)O, and changes in glycogen and fat content in liver and muscle were measured by (13)C and (1)H magnetic resonance spectroscopy, respectively. Exercise resulted in a greater than threefold increase in postprandial 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 postprandial 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.

Nonalcoholic fatty liver disease is an increasingly common condition that may progress to hepatic cirrhosis. This pilot study evaluated the effects of a low-carbohydrate, ketogenic diet on obesity-associated fatty liver disease. Five patients with a mean body mass index of 36.4 kg/m(2) and biopsy evidence of fatty liver disease were instructed to follow the diet (<20 g/d of carbohydrate) with nutritional supplementation for 6 months. Patients returned for group meetings biweekly for 3 months, then monthly for the second 3 months. The mean weight change was -12.8 kg (range 0 to -25.9 kg). Four of 5 posttreatment liver biopsies showed histologic improvements in steatosis (P=.02) inflammatory grade (P=.02), and fibrosis (P=.07). Six months of a low-carbohydrate, ketogenic diet led to significant weight loss and histologic improvement of fatty liver disease. Further research is into this approach is warranted.