Fatty Acids and Exercise Affect Glucose Transport But Not Tumour Growth in F-344 Rats

Abstract

This study examined the effect of diet and exercise on tumour growth, and the effect of dietary fatty acids on glucose uptake. Male Fischer 344 rats were divided into 4 dietary groups and fed for 2 weeks. The diets were 5% (wt/wt) safflower oil, 10% safflower oil, 5% docosahexaenoic acid(DHA)-rich, and 10% DHA-rich. On Day 14 the animals were injected with rat fibrosarcoma tumour cells. After 3 days of tumour growth the animals in each diet group were divided into exercise and nonexercise groups. Exercise was achieved by voluntary wheel running. Dietary intake, body weight, tumour growth, and distance run were determined daily. Two weeks later the animals were euthanized and the following tissues were dissected out: tumour, liver, heart, epididymal fat pads, gastrocnemius, epitrochlearis, and soleus muscles. Glucose transport experiments were performed on the epitrochlearis and soleus muscles whereas phospholipid analysis was completed on the gastrocnemius muscle. We observed no effect of either diet or exercise on tumour growth. The glucose transport data demonstrates that short-term voluntary running can cause increased insulin-sensitive transport and that DHA may inhibit transport. DHA-containing diets were associated with increased oxidation products TBARM. In conclusion, exercise benefits on glucose disposal are maintained in tumour-bearing animals but are influenced by fat content and composition. High DHA diets may also increase oxidative damage in muscle through enhanced TBARM production.

Effects and potential mechanisms of exercise training on cancer progression: A translational perspective

“…Finally, in three studies tumor growth was comparable between exercise and sedentary control groups (Foley et al, 2004; Jones et al, 2005, 2010b). Foley et al found no effect of 17 days of voluntary wheel running following subcutaneous injection of C10 sarcoma cells in F344 rats (Foley et al, 2004).…”

“…Surprisingly, while numerous research groups have utilized mouse models to examine the effects of exercise on the initiation and incidence of several different cancer types (i.e., exercise exposure followed by tumor initiation), far fewer have adopted this experimental system to investigate the effects of exercise on progression and metastasis (i.e., initiation of exercise following tumor establishment, which mimics the clinical scenario of using exercise as an adjunct cancer therapy). As summarized in Table 4, we found a total of 14 studies investigating the effects of endurance exercise on a variety of different tumor types and endpoints, in several different model systems (Baracos, 1989; Cohen et al, 1991; Foley et al, 2004; Hoffman et al, 1962; Hoffman-Goetz et al, 1994b; Japel et al, 1992; Jones et al, 2005, 2010b; MacNeil and Hoffman-Goetz, 1993; Roebuck et al, 1990; Saez Mdel et al, 2007; Uhlenbruck and Order, 1991; Zheng et al, 2011; Zielinski et al, 2004). In summary, 11 (79%) studies reported primary tumor growth as an endpoint; of these, four found that exercise resulted in inhibition of primary tumor growth (Baracos, 1989; Cohen et al, 1991; Hoffman et al, 1962; Zheng et al, 2011).…”

“…Foley et al found no effect of 17 days of voluntary wheel running following subcutaneous injection of C10 sarcoma cells in F344 rats (Foley et al, 2004). Jones et al observed similar results in two independent experiments in a model of human breast cancer.…”

“…More recently, we found that voluntary wheel running increased hypoxia-inducible factor-1 protein levels and number of perfused blood vessels in athymic mice bearing human breast cancer xenografts, although there were no differences in protein levels of 5′ adenosine monophosphate-activated protein kinase, which regulates cellular energy homeostasis, or the angiogenic markers CD31 (a marker of endothelial cells) and vascular endothelial growth factor (Jones et al, 2010b). Two (14%) studies have examined changes in circulating concentrations of various growth factors with exercise, with both finding no changes in systemic glucose or prolactin levels (Cohen et al, 1991; Foley et al, 2004). Additionally, two studies investigated immune effects of exercise.…”

High-Fat and Fat-Enriched Diets Impair the Benefits of Moderate Physical Training in the Aorta and the Heart in Rats

“…Thus, we should remember that an increased fat intake alters the mitochondrial bioenergetics, blocking the hepatic and skeletal muscle uptake of glucose, which then augments its serum levels (49, 52). Interestingly, a report revealed that short-term voluntary running for 2 weeks promoted the insulin activity, improving the muscle-related glucose transport in mice (53). These data drove our attention toward hepatic metabolism.…”