The goal of this study by Moore et al. was to investigate whether preventing thiazolidinedione (TZD)-induced hyperphagia by energy restriction in dietary obese rats would enhance the insulin-sensitizing effects of rosiglitazone treatment at a therapeutic dose and, within this paradigm, to produce an original survey of candidate TZD-gene targets in the clinically relevant intra-abdominal (visceral) white adipose tissue. For that purpose, they studied 2 groups of dietary obese rats, either freely fed or energy restricted, treated with rosiglitazone for 2 weeks. Half of the TZD-treated dietary obese rats were pair-fed to match the food intake of the placebo-treated dietary obese controls. Results of this study indicated that in comparison with untreated dietary obese controls, rosiglitazone improved insulin sensitivity by reducing plasma insulin levels as well as free fatty acid and triglyceride levels in both freely fed and pair-fed groups. These effects appeared to be greater in pair-fed animals, suggesting that energy restriction further improved insulin sensitivity. The authors also found that rosiglitazone treatment altered the expression of several genes expressed in the intra-abdominal depot, such as leptin, resistin, fatty acid transport protein (FATP)-1, fatty acid synthase (FAS), and heart fatty acid-binding protein (H-FABP). These results indicate that energy restriction enhances the therapeutic efficacy of TZDs and suggest that this effect is due in part to a modulation of gene expression in intra-abdominal white adipose tissue.
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