No abstract

Non-small cell lung cancer (NSCLC) accounts for 85% of all lung cancer cases, and for the most cancer-related deaths. The survival pathway of Akt, its downstream effectors, the mammalian target of rapamycin (mTOR) and ribosomal protein S6 kinase (p70 S6K), and the Ras-extracellular signal-regulated kinase (Erk1/2) pathways are activated in cancer leading to cell survival and growth. Thus, approaches that inhibit these signaling molecules may prove useful in the fight against lung cancer. Exercise is associated with health benefits and a limited number of studies indicate that serum from physically active individuals inhibit mammary and prostate cancer cell growth. In this study, we examined the effects of post exercise serum on proliferation, survival, and signaling cascades of human NSCLC cells. Blood was collected from male subjects prior to, 5 min, 1 h, and 24 h after a single bout of high intensity interval exercise on a cycle ergometer. Exposure of NSCLC cells to post exercise serum resulted in the inhibition of cell proliferation and survival, as well as significant reduction of phosphorylated/activated Akt, mTOR, p70 S6K, and Erk1/2 levels compared to cells treated with serum taken pre-exercise. Our data suggest that post exercise serum has anti-cancer properties in lung cancer and deserves further systematic investigation in animal models.

Obesity results from a caloric imbalance between energy intake, absorption and expenditure. In both rodents and humans, diet-induced thermogenesis contributes to energy expenditure and involves the activation of brown adipose tissue (BAT). We hypothesize that environmental toxicants commonly used as food additives or pesticides might reduce BAT thermogenesis through suppression of uncoupling protein 1 (UCP1) and this may contribute to the development of obesity. Using a step-wise screening approach, we discover that the organophosphate insecticide chlorpyrifos suppresses UCP1 and mitochondrial respiration in BAT at concentrations as low as 1 pM. In mice housed at thermoneutrality and fed a high-fat diet, chlorpyrifos impairs BAT mitochondrial function and diet-induced thermogenesis, promoting greater obesity, non-alcoholic fatty liver disease (NAFLD) and insulin resistance. This is associated with reductions in cAMP; activation of p38MAPK and AMPK; protein kinases critical for maintaining UCP1 and mitophagy, respectively in BAT. These data indicate that the commonly used pesticide chlorpyrifos, suppresses diet-induced thermogenesis and the activation of BAT, suggesting its use may contribute to the obesity epidemic.

No abstract

Obesity is a leading cause of morbidity, mortality and health care expenditure whose incidence is rapidly rising across the globe. Although the cause of the obesity epidemic is typically viewed as a product of an increased availability of high calorie foods and/or a reduction in physical activity, there is mounting evidence that exposure to synthetic chemicals in our environment may play an important role. Pesticides, are a class of chemicals whose widespread use has coincided with the global rise of obesity over the past two decades. Importantly, given their lipophilic nature many pesticides have been shown to accumulate with adipose tissue depots, suggesting they may be disrupting the function of white adipose tissue (WAT), brown adipose tissue (BAT) and beige adipose tissue to promote obesity and metabolic diseases such as type 2 diabetes. In this review, we discuss epidemiological evidence linking pesticide exposure with body mass index (BMI) and the incidence of diabetes. We then review preclinical studies in rodent models which have directly evaluated the effects of different classes of insecticides and herbicides on obesity and metabolic dysfunction. Lastly, we review studies conducted in adipose tissue cells lines and the purported mechanisms by which pesticides may induce alterations in adipose tissue function. The review of the literature reveals major gaps in our knowledge regarding human exposure to pesticides and our understanding of whether physiologically relevant concentrations promote obesity and elicit alterations in key signaling pathways vital for maintaining adipose tissue metabolism.