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Chronic endurance exercise is a therapeutic strategy in the treatment of many chronic diseases in humans, including the prevention and treatment of metabolic diseases such as diabetes mellitus. Metabolic, cardiorespiratory, and endocrine pathways targeted by chronic endurance exercise have been identified. In the liver, however, the cellular and molecular pathways that are modified by exercise and have preventive or therapeutic relevance to metabolic disease need to be elucidated. The mouse model used in the current study allows for the quantification of a human-relevant exercise “dosage”. In this study we show hepatic gene expression differences between sedentary female and sedentary male mice and that chronic exercise modifies the transcription of hepatic genes related to metabolic disease and steatosis in both male and female mice. Chronic exercise induces molecular pathways involved in glucose tolerance, glycolysis, and gluconeogenesis while producing a decrease in pathways related to insulin resistance, steatosis, fibrosis, and inflammation. Given these findings, this mouse exercise model has potential to dissect the cellular and molecular hepatic changes following chronic exercise with application to understanding the role that chronic exercise plays in preventing human diseases. Novelty: Exercise modifies the hepatic gene expression and hepatic pathways related to metabolic disease in male and female mice. Sex differences were seen in hepatic gene expression between sedentary and exercised mice. The mouse exercise model used in this study allows for application and evaluation of exercise effects in human disease.

Persistent organic pollutants (POPs) are a group of organic chemicals, as defined by the Stockholm Convention that are persistent in the environment and accumulate in organisms including humans. Most POPs are restricted in use or no longer manufactured because of this persistence, bioaccumulation, and toxicity. In addition, an association between POP exposure and human disease has been suggested. Regarding toxicological effects and particularly cancer, most POPs have been shown to induce hepatic tumors when chronically administered to rodents. Understanding the mechanisms by which POPs induce liver cancer is important in developing meaningful human cancer risk evaluation to these compounds. In this article, we have reviewed the probable mechanisms of hepatic cancer induced by POPs mode of action and molecular initiating events and the relationship of these mechanisms to potential human cancer risk.

Chronic endurance exercise is a therapeutic strategy in the treatment of non‐alcoholic fatty liver disease (NAFLD). Metabolic, cardiorespiratory, and endocrine pathways targeted by chronic endurance exercise have been identified; however, the specific cellular and molecular pathways modified by exercise in the steatotic liver remain unresolved. In this study, we show hepatic gene expression, and the structure, characteristics, and clinical differences between sedentary and exercised mice, by an endurance exercise model with wheels with a controlled velocity that allows for the quantification of a human‐relevant endurance “dosage,” after exposure to regular and high‐fat diet. Chronic exercise modified the transcription of hepatic genes related to liver nuclear receptors, cell growth, fibrosis, inflammation, and oxidative stress, and decreased the amount of lipid accumulation in the liver. Moreover, the combination of endurance training with the change in diet differentially modified the genetic expression of the biomarkers relative to the separate interventions. Even though exercise by itself showed counteract NAFLD development, the combined intervention was sufficient to convert the structure and clinical aspects of the liver from steatotic to healthy. Given our findings, the combination of endurance exercise and change in diet should be considered a therapeutic option for NASH., Chronic exercise ameliorated fibrosis, inflammation, and oxidative stress, through the transcription of hepatic genes related to liver nuclear receptors, cell growth, fibrosis, inflammation, and oxidative stress. Chronic exercise decreased the amount of high‐fat diet‐induced lipid accumulation in the liver. The combination of endurance exercise and change of diet should be considered a therapeutic option for NASH.

Background Aerobic exercise has been shown to slow tumor progression in rodents and humans, but the mechanisms behind this effect are still unclear. Here we show that aerobic exercise in the form of chronic endurance training suppresses tumor recruitment of FoxP3+ Treg cells thus enhancing antitumor immune efficiency. Methods Adult wild-type and athymic BALB/c female mice were endurance-trained for 8 weeks. Circulating leukocytes as well as muscle and liver mtDNA copy number were compared to aged-matched concurrent sedentary controls to establish systemic effects. 4 T1 murine mammary tumor cells were injected subcutaneously to the 4th mammary pad at the end of the training period. Tumor growth and survival rates were compared, together with antitumor immune response. Results Exercised wild-type had 17% slower growth rate, 24% longer survival, and 2-fold tumor-CD+ 8/FoxP3+ ratio than sedentary controls. Exercised athymic BALB/c females showed no difference in tumor growth or survival rates when compared to sedentary controls. Conclusions Cytotoxic T cells are a significant factor in endurance exercise-induced suppression of tumor growth. Endurance exercise enhances antitumor immune efficacy by increasing intratumoral CD8+/FoxP3+ ratio. Electronic supplementary material The online version of this article (10.1186/s12885-019-5745-7) contains supplementary material, which is available to authorized users.

Given the known clinical utility of cardiorespiratory fitness, measurement of physiological responses to submaximal exercise may be a feasible approach well suited for diagnostic and prognostic purposes in non-athletes and the chronically ill. Lactate levels and watt output during a short submaximal exercise and a subsequent relaxation period yield an aerobic score that is consistent with cardiorespiratory fitness grades in non-athletes and that may be used as a marker in such approaches. In this study, 28 females (23 ± 3 years) were submitted to a 15 min submaximal recumbent bike session, and their capillary and saliva lactate concentrations were recorded and plotted against time. An individual aerobic score was calculated from this curve, using watt output during equal relative percentiles of maximum heart-rate benchmarks. The scores were compared with respective results in a V̇O2max test and with a similar scoring system in 14 older (51 ± 9 years) females; they correlated with the 6 categories of the V̇O2max test results and classified into 3 categories of V̇O2max grades (very poor/poor; fair/good; excellent/superior) with a combined accuracy of 80.95%. More studies are required to validate the potential utility of this submaximal test as an additional risk factor for diagnostic purposes in non-athletes. Novelty points: A novel method for estimating cardiorespiratory fitness during submaximal exercise consistent with V̇O2max performance. The method yields an aerobic score that may be used as a marker for diagnostic and prognostic purposes.