Acutely reduced locomotor activity is a major contributor to Western diet-induced obesity in mice

1 AstraZeneca R&D, Mölndal; and 2 Department of Physiology/Endocrinology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, Göteborg University, Göteborg, Sweden Submitted 25 June 2007 ; accepted in final form 13 November 2007 The aim of the present study was to investigate the short- and long-term effects of a high-fat Western diet (WD) on intake, storage, expenditure, and fecal loss of energy as well as effects on locomotor activity and thermogenesis. WD for only 24 h resulted in a marked physiological shift in energy homeostasis, including increased body weight gain, body fat, and energy expenditure (EE) but an acutely lowered locomotor activity. The acute reduction in locomotor activity was observed after only 3–5 h on WD. The energy intake and energy absorption were increased during the first 24 h, lower after 72 h, and normalized between 7 and 14 days on WD compared with mice given chow diet. Core body temperature and EE was increased between 48 and 72 h but normalized after 21 days on WD. These changes paralleled plasma T 3 levels and uncoupling protein-1 expression in brown adipose tissue. After 21 days of WD, energy intake and absorption, EE, and body temperature were normalized. In contrast, the locomotor activity was reduced and body weight gain was increased over the entire 21-day study period on WD. Calculations based on the correlation between locomotor activity and EE in 2-h intervals at days 21–23 indicated that a large portion of the higher body weight gain in the WD group could be attributed to the reduced locomotor activity. In summary, an acute and persisting decrease in locomotor activity is most important for the effect of WD on body weight gain and obesity in mice. energy balance; high-fat diet; energy expenditure; calorimetry Address for reprint requests and other correspondence: M. Bjursell, AstraZeneca R&D Mölndal, S-43183 Mölndal, Sweden (e-mail: mikael.bjursell{at}astrazeneca.com )