Defective brown adipose oxygen consumption in obese Zucker rats.

The thermogenic capacity and morphologic characteristics of interscapular brown adipose tissue (IBAT) were assessed in 3- to 4-mo-old male, lean and obese Zucker rats. Pads from obese rats were threefold heavier and contained similar numbers of cells but an average of 50% fewer multilocular cells than pads from lean rats and 40% less mitochondrial protein per pad. The maximal number of beta-adrenoreceptor binding sites, as assessed by [125I]iodocyanopindolol binding to isolated brown adipocytes from obese rats was 50% of that in lean rats on a per cell and per pad basis. Basal and norepinephrine (NE)-stimulated in vitro oxygen consumption in isolated brown adipocytes from lean rats correlated directly with the proportion of mutilocular cells present. This correlation was not seen in cells from obese rats that had a 50% decrease in their basal respiratory rates and could not be further stimulated by excess NE or fatty acid. Electron micrographs of IBAT from obese rats revealed distorted mitochondrial shapes and cristae patterns and the presence of numerous inclusion bodies. Because NE-stimulated lipolysis had previously been shown to be normal in the obese Zucker rat, these data suggest that defective BAT thermogenesis in the obese rat is due to an inability of mitochondria to utilize free fatty acids for the production of enhanced oxygen consumption.