Fibroblast cell lines, designated R-and W cells, were generated, respectively, from mouse embryos homozygous for a targeted disruption of the Igflr gene, encoding the type 1 insulin-like growth factor receptor, and from their wild-type littermates. W cells grow normally in serum-free medium supplemented with various combinations of purified growth factors, while pre-and postcrisis R-cells cannot grow, as they are arrested before entering the S phase. R-cells are able to grow in 10% serum, albeit more slowly than W cells, and with all phases of the cell cycle being elongated. An activated Ha-ras expressed from a stably transfected plasmid is unable to overcome the inability of R-cells to grow in serum-free medium supplemented with purified growth factors but stimulates their growth in 10% serum and also induces the formation of small foci in some clones. Nevertheless, even in the presence of serum, R-cells stably transfected with Ha-ras, alone or in combination with simian virus 40 large T antigen, fail to form colonies in soft agar. Reintroduction into Rcells (or their derivatives) of a plasmid expressing the human insulin-like growth factor I receptor RNA and protein restores their ability to grow with purified growth factors or in soft agar. The signaling pathways participating in cell growth and transformation are discussed on the basis of these results.

Two metabolic pathways of the white adipocytes (i.e. de novo lipogenesis and lipolysis) require mitochondria functionality. In this report, the oxidative capacity of two white adipose tissues of rat and their respective isolated adipocytes were evaluated. Two major white fat pads, namely inguinal and epididymal tissues, were chosen as subcutaneous and visceral adipose tissues, respectively. The mitochondrial content of these tissues was estimated using cytological and biochemical analysis. Electron microscopy analysis showed higher mitochondrial density in epididymal than in inguinal adipocytes. The mitochondrial DNA content and mitochondrial enzymatic equipment were also higher in the former than in the latter tissue. A positive correlation between two mitochondrial enzymatic activities, namely cytochrome c oxidase and citrate synthase, and the mtDNA content of adipose tissue was reported. Moreover, NRF1 protein, which belongs to the transcriptional activator family and is thought to be involved in mitochondrial biogenesis regulation, was present in higher proportions in nuclei isolated from epididymal cells than in those from inguinal cells. Finally, greater abundance of mitochondria in epididymal tissue is in agreement with higher cytochrome c oxidase activity as well as increased respiration (i.e. basal and noradrenaline-stimulated) of adipocytes isolated from epididymal tissue as compared to adipocytes isolated from inguinal tissue. Therefore, white adipose tissue appears as a heterogeneous organ with marked variation in mitochondrial content depending on its anatomical location.

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