Skeletal muscle wasting in tumor-bearing rats is associated with MyoD down-regulation.

Cachexia is a syndrome characterized by profound skeletal muscle wasting that frequently complicates malignancies. A number of studies indicate that protein hypercatabolism, largely mediated by classical hormones and cytokines, is the major component of muscle depletion. Impaired regeneration has been suggested to contribute to the reduction of muscle size. In particular, it has been shown that the expression of MyoD, a muscle-specific transcription factor, is down-regulated by cytokines such as TNFalpha and IFNgamma in a NF-kappaB-dependent posttranscriptional manner. The present study investigated whether modulations of the transcription factor MyoD are associated with the onset of muscle wasting in a well established model of cancer cachexia. Rats bearing the Yoshida AH-130 hepatoma develop a condition of muscle protein hypercatabolism, largely dependent on TNFalpha bioactivity. In the gastrocnemius of these animals the expression of MyoD was markedly reduced, paralleling the decrease of muscle weight. This pattern is associated with increased nuclear translocation of AP-1, while DNA-binding assays did not detect any change in NF-kappaB activity. This is the first observation demonstrating that muscle depletion in tumor-bearing rats is associated with a down-regulation of MyoD levels. Although the underlying mechanisms remain to be clarified, this change is compatible with the hypothesis that a reduced expression of molecules involved in the regulation of the regenerative response may concur to muscle wasting in cancer cachexia.

High-sensitivity C-reactive protein and liver enzymes in individuals with Metabolic Syndrome in Talca, Chile.

Metabolic syndrome (MS) is a core set of disorders, including abdominal obesity, dyslipidemia, hypertension and hypertriglyceridemia that together predict the development of diabetes type 2 and cardiovascular disease. This study investigated the relationship between liver enzyme levels and high-sensitivity C-reactive protein (hs-CRP) in subjects with and without MS. Alanine-aminotransferase (ALAT), aspartate-aminotransferase (ASAT), γ-glutamyl transferase (GGT) and hs-CRP were measured in 510 subjects, aged 40 to 65 years old. Patients were selected from 1007 subjects from the Research Program for Cardiovascular Disease Risk Factors in Talca, Chile. Results showed that women with MS presented higher liver enzyme levels than those who did not have MS. This was not observed in male patients for the enzymes ALAT and ASAT. However, GGT and hs-PCR levels were higher in male and female patients with MS than in those without MS. In conclusion, it is important to search for the presence of MS when diagnosing fatty liver. Moreover, the presence of liver disease in patients with MS should be further investigated.

A high fat diet in CF-1 mice: An experimental model for metabolic syndrome.

Cardiovascular diseases account for the majority of deaths worldwide. Many of their risk factors have been identified but, for their continued study, research centering on new murine models is of interest. In this study, a high fat diet (HFD) and a normal diet (ND) (25 and 4.4% fat, respectively) were tested over a 40-day period to induce the same metabolic alterations in CF-1 mice in two separate experiments. The parameters measured for these effects corresponded to the weight of ingested food and water, to the weight of the mice and their selected organs (adipose tissue, gastrocnemius, liver and heart), to their biochemical profile (glycemia, blood uric nitrogen, uric acid, triglycerides, cholesterol, proteins and albumin) and to the percentage of fat in their livers. The biochemical profile of the CF-1 mice fed a diet high in fat but balanced in proteins (16.9%) showed statistically significant increases in glycemia, cholesterol and triglyceride levels. A statistically significant increase in the weight of adipose tissue was also observed. No statistically significant differences were observed in the muscular mass of either of the groups of mice, but a high percentage of fat was found in the liver. The results lead to the conclusion that CF-1 mice fed a HFD develop metabolic alterations that correspond to an equivalent metabolic syndrome. This is important in the evaluation of the effects of various interventions, such as food, exercise and molecules, on metabolic alterations in mice induced by the intake of a HFD.