Mitochondrial dysfunction in non-alcoholic fatty liver disease and insulin resistance: cause or consequence?

Non-alcoholic fatty liver disease (NAFLD) is considered the hepatic manifestation of the metabolic syndrome and refers to a spectrum of disorders ranging from steatosis to steatohepatitis, a disease stage characterized by inflammation, fibrosis, cell death and insulin resistance (IR). Due to its association with obesity and IR the impact of NAFLD is growing worldwide. Consistent with the role of mitochondria in fatty acid (FA) metabolism, impaired mitochondrial function is thought to contribute to NAFLD and IR. Indeed, mitochondrial dysfunction and impaired mitochondrial respiratory chain have been described in patients with non-alcoholic steatohepatitis and skeletal muscle of obese patients. However, recent data have provided evidence that pharmacological and genetic models of mitochondrial impairment with reduced electron transport stimulate insulin sensitivity and protect against diet-induced obesity, hepatosteatosis and IR. These beneficial metabolic effects of impaired mitochondrial oxidative phosphorylation may be related not only to the reduction of reactive oxygen species production that regulate insulin signaling but also to decreased mitochondrial FA overload that generate specific metabolites derived from incomplete FA oxidation (FAO) in the TCA cycle. In line with the Randle cycle, reduced mitochondrial FAO rates may alleviate the repression on glucose metabolism in obesity. In addition, the redox paradox in insulin signaling and the delicate mitochondrial antioxidant balance in steatohepatitis add another level of complexity to the role of mitochondria in NAFLD and IR. Thus, better understanding the role of mitochondria in FA metabolism and glucose homeostasis may provide novel strategies for the treatment of NAFLD and IR.

Adenosine A(3) receptors regulate heart rate, motor activity and body temperature.

AIM: To examine the phenotype of mice that lack the adenosine A(3) receptor (A(3)R). METHODS: We examined the heart rate, body temperature and locomotion continuously by telemetry over several days. In addition, the effect of the adenosine analogue R-N(6)-phenylisopropyl-adenosine (R-PIA) was examined. We also examined heat production and food intake. RESULTS: We found that the marked diurnal variation in activity, heart rate and body temperature, with markedly higher values at night than during day time, was reduced in the A(3)R knock-out mice. Surprisingly, the reduction in heart rate, activity and body temperature seen after injection of R-PIA in wild type mice was virtually eliminated in the A(3)R knock-out mice. The marked reduction in activity was associated with a decreased heat production, as expected. However, the A(3)R knock-out mice, surprisingly, had a higher food intake but no difference in body weight compared to wild type mice. CONCLUSIONS: The mice lacking adenosine A(3) receptors exhibit a surprisingly clear phenotype with changes in diurnal rhythm and temperature regulation. Whether these effects are due to a physiological role of A(3) receptors in these processes or whether they represent a role in development remains to be elucidated.

Comparison of dietary intake and eating behavior of professional road cyclists during training and competition.

The dietary intake and eating behavior of a group of professional elite road cyclists during high intensity training and competition was compared. Their eating pattern consisted of several snacks throughout the race or training, a meal eaten no later than 1 hr postexercise, supper, and breakfast. Protein intake showed a significant difference between evaluation times expressed in three ways: per total amount intake, by kg body weight, and percentage of energy supplied. Due to the high energy intake of these cyclists during training and competition (22.9 +/- 1.5, 22.4 +/- 1.7 MJ, respectively) they presented a high consumption of each macronutrient both in competition and in training. The eating behavior of these athletes was similar during breakfast (possibility to choose from among approximately 25 foods) and supper (set menu), with variation in the energy intake and a similar relative contribution of the different macronutrients. In general, it is possible to consider the professional road cyclists as a homogeneous group with a similar nutrition intake, eating habits, and nutritional needs throughout the more demanding periods of the season. Furthermore, differences found in protein intake between periods could not be explained by differences in the food available in competition and training periods.

Macronutrients intake of top level cyclists during continuous competition--change in the feeding pattern.

In order to quantify the nutritional status and the feeding pattern of professional cyclists during continuous competition, food intake was accurately measured and recorded using the weighed inventory of food (over three 24 h periods) during all meals in ten top professional cyclists during a real 3 weeks' competition. A 24 h period was defined as the time between the start of one stage and the next start. The 24 h period intake of energy, protein, fat, and carbohydrate was used to discover whether these intakes met requirements for endurance exercise. The average intake of energy and macronutrients was: energy = 23.5 +/- 1.8 MJ/24 h period, carbohydrate = 841.4 +/- 66.2 g/ 24h period; protein = 201.8 +/- 17.7g/24 h period; and fat = 158.6 +/- 16.3 g/24 h period. The carbohydrate, protein and fat contribution to energy was 60.0%, 14.5%, and 25.5% respectively. Fluid intake per 24h period was 3.29 +/- 0.94l (1.26 +/- 0.55 l during the race). Our study shows a similar energy intake in comparison with the only previous study in 1989 but there is a change in the feeding pattern of top level cyclists. A more important role is given to the intake of carbohydrate just after competitions together with an increase in protein intake. Both changes could have a positive effect on performance.