Inactivity and fat cell hyperplasia: fat chance?

IT IS NO SECRET THAT OBESITY and obesity-related metabolic disorders are rising unabated in the United States (5, 6), and this epidemic has not eluded children. From 1999 –2000 to 2003–2004, the prevalence of overweight children/adolescents increased from 13.8 to 16.0% for males and 14.0 to 18.2% for females (13). Of the three major actual causes of death (tobacco , poor diet, and physical inactivity) as classified by the Centers for Disease Control (12), physical inactivity has received the least attention. One paradigm of physical inactivity is based on the premise that physically active subjects (or animals) should be the control group (2). Using a young animal model consuming 17% of their diet as fat calories, Booth and colleagues have established in a series of eloquent studies that incorporation of voluntary running wheel lock, inducing physical inactivity (for ϳ2 days) after a period of voluntary physical activity (Ͼ3 wk), results in a rapid loss of submaximal insulin stimulated 2-deoxyglucose uptake into epitrochlearis muscle, mediated, at least in part, through decreases in insulin receptor ␤-subunit protein, insulin receptor ␤-subunit tyrosine phosphorylation, GLUT4 and Akt phosphorylation (7), and a rise in palmitate incorporation into triglyceride (TG; an index of triglyceride synthesis) in epididymal adipose tissue (8), mediated, in part, by an increase in mitochondrial glycerol-3-phosphate acyltransferase, a key regulator of TG synthesis (9). These changes were associated with increases in both plasma insulin and TG ϳ2 days after wheel lock. Additionally, this group noted an increase in abdominal fat accumulation after ϳ2 days of wheel lock. In these studies, animals were fed ad libitum and consumed more food than sedentary rats during activity and wheel-lock phases, raising the possibility that the increase in abdominal adiposity was simply due to the inability of the animals to acutely regulate their food intake with inactivity, resulting in caloric excess. In their current study in this issue of the Journal of Applied Physiology, Laye et al. (10) set out to determine whether 1) the increase in abdominal adiposity was simply a function of excess food intake during wheel lock; 2) extension of the wheel lock would indicate a transient effect; and 3) an increase in abdominal fat was maintained, and whether the increase in abdominal fat noted was explained by an increase in adipocyte hypertrophy and/or hyperplasia. To test these hypotheses, the authors employed a pair-feeding model and a 1-wk wheel-lock phase. Laye et al. (10) …