Rat adipocyte utilization of different substrates: effects of cell size and the control of lipogenesis

The metabolism of labeled glucose, pyruvate and acetate was compared in adipocytes isolated from old, obese rats (greater than 500 g) and young, lean rats (130-150 g). The larger cells from old, obese rats had markedly reduced rates of glucose, pyruvate and acetate conversion to glyceride-fatty acids, indicating that large cell fatty acid formation is reduced at some point beyond the entry of pyruvate and acetate into glucose metabolism. No evidence of a primary block in the pentose phosphate cycle of cells from old, obese rats was found. In spite of diminished glucose metabolism to several products in the large cells, both basal and insulin-stimulated rates of glyceride-glycerol synthesis from glucose and pyruvate were similar in each cell type. This indicates a relative diversion of carbon flow to alpha-glycerophosphate and reesterification in the large cells. Addition of low concentrations of glucose increase glyceride-fatty acid synthesis from acetate (both cell types) or pyruvate carbon (small cells), but decreased glyceride-glycerol synthesis from pyruvate carbon (both cell types). The acceleration of small cell fatty acid synthesis from pyruvate carbon by glucose and insulin was shown to be related to provision of NADPH from glucose metabolism in the pentose cycle. These studies indicate that, although the block in lipogenesis in adipocytes from old, obese rats appears to reside in the pathway of fatty acid synthesis itself, provision of additional alpha-glycerophosphate or NADPH from glucose metabolism may, under certain conditions, increase lipogenesis in cells from old, obese and young, lean rats.