Decreased intestinal polyp multiplicity is related to exercise mode and gender in Apc^Min/+ mice

Abstract

Moderate-intensity treadmill running can alter male Apc(Min/+) mouse polyp formation. This purpose of this study was to examine whether exercise mode differentially affects Apc(Min/+) mouse intestinal polyp development in male and female mice. Male and female Apc(Min/+) mice were randomly assigned to control, treadmill (18 m/min; 60 min/day; 6 days/wk), or voluntary wheel running (24-h access) groups. Nine weeks of training decreased total intestinal polyps by 29% in male treadmill runners (66 +/- 9; P = 0.038) compared with male controls (93 +/- 7). The number of large polyps (>/=1-mm diameter) were also reduced by 38% in male treadmill runners (49 +/- 6; P = 0.005) compared with male controls (79 +/- 6). Treadmill running in female Apc(Min/+) mice and wheel running in both genders did not affect polyp number or size. Spleen weight decreased in male treadmill runners (91 +/- 9 mg; P = 0.011) and wheel runners (75 +/- 6 mg; P = 0.004) compared with controls (141 +/- 13 mg). Plasma IL-6 was reduced by 96% in male treadmill runners (1.2 +/- 0.6 pg/ml) and 78% in male wheel runners (6.6 +/- 3.3 pg/ml) compared with control mice (27.9 +/- 2.8 pg/ml; P < 0.05). Female mice responded similarly with an 86% decrease in plasma IL-6 with treadmill running (3.2 +/- 1.2 pg/ml) and 90% decrease with wheel running (2.9 +/- 2.0 pg/ml) compared with control mice (21.1 +/- 5.3 pg/ml; P < 0.05). The crypt depth-to-villus height ratio in the intestine, an indirect marker of intestinal inflammation, decreased by 21 (P = 0.024) and 24% (P = 0.029), respectively, in male and female treadmill runners but not wheel runners. Physical activity-induced attenuation of intestinal polyp number and size is dependent on exercise mode and differs between genders. The modulation of systemic and intestinal inflammation may also depend on exercise mode.

Altered intestinal epithelium-associated lymphocyte repertoires and function in ApcMin/+ mice

“…As reported previously (37,38), the number of adenomas increased along the proximal-distal axis of the small intestine in Apc Min/+ mice (proximal = 8.31±1.1, middle = 22.1±2.6, distal = 46.31±3.1; p<0.001), which was also seen in Apc Min/+ TcRδ -/-mice (proximal = 6.1±1.1, middle=12.37±4.7, distal=18±4.9; p<0.005) (Fig. 3B).…”

Muscle oxidative capacity during IL-6-dependent cancer cachexia

“…Min/ϩ mouse, a genetic model of colon cancer (39), there is a greater loss of gastrocnemius type IIb fiber cross-sectional area compared with type IIa fiber (8). This selectivity to wasting stimuli may be related to oxidative muscle fibers having an increased tolerance for systemic inflammation and metabolic alterations that occur with many wasting diseases (56).…”

“…We previously demonstrated that tumor bearing, weight-stable Apc Min/ϩ mice have similar gastrocnemius muscle citrate synthase activities and functional capacity related to distance run in voluntary activity wheels compared with wild-type (WT) mice. (39). The purpose of this study was to determine the relationship between muscle oxidative capacity and muscle mass loss in primarily red and white hindlimb muscles during the development of cancer cachexia in the Apc Min/ϩ mouse.…”

CARD9 Promotes Sex-Biased Colon Tumors in the APCmin Mouse Model

“…B, plasma cytokine concentrations from male understanding this phenomenon. In other studies, increased plasma IL6 is coincident with cachexia in male APC min mice but not female APC min mice (25). It may be that CARD9 is functioning upstream of plasma IL6 in male APC min mice to enhance cachexia and reduce viability, potentially through Th17-cell induction.…”