Rat adipocyte precursor populations contain clones varying in capacity for replication. In this study we explored factors controlling the frequency of clones of varying replicative capacities (clonal composition). We also explored the relationship between this frequency and fat depot growth.In perirenal and epididymal depots clonal composition was identical bilaterally; perirenal depots contained more extensively replicating clones. Although there were large interanimal differences in clonal composition, variation between animals was always in the same direction for both depots. Clonal composition was unaffected by undernutrition while with animal growth the frequency of the most extensively replicating clones was reduced. Differentiation of precursors occurred in all clones, while differentiation did not occur in skin fibroblasts cloned under identical conditions. Clonal composition and mature fat cell number were related in that fat cell numbers were identical bilaterally in both depots and increased more extensively with growth in perirenal than epididymal tissue.We conclude (a) that clonal composition of adipocyte precursor populations is regulated genetically and by age, (b) that this composition determines, at least in part, the capacity for adipose depot growth.

OBJECTIVES To understand the mechanism of white fat expansion in the presence of inflammation, we examined the balance of pro- and anti-inflammatory cytokines in epididymal fat during weight gain in DIO mice. METHODS The pro- and anti-inflammatory cytokines were examined in white fat of diet-induced obese mice and lean mice. The mechanism of gene expression was investigated with a focus on intracellular ATP (iATP). ATP activity was tested in cellular and non-cellular systems in activation of serine kinases (IKKβ, JNK and ERK). RESULTS The pro- (TNF-α, IL-1β, IL-6, MCP-1, IFN-γ and OPN) and the anti-inflammatory cytokines (IL-10, IL-1Ra, IL-13, sTNFR2, PEDF and adiponectin) were increased at the same time during the weight gain. The balance was observed even in the absence of tissue expansion upon feeding in lean and obese mice. The iATP levels were positively associated with the cytokine elevation in the adipose tissue. In macrophages, induction of iATP with lauric acid stimulated the expression. Inhibition of iATP with β-oxidation inhibitor (Etomoxir) or mitochondrial uncoupler (2,4-dinitrophenol, DNP) suppressed the expression. ATP exhibited an activity in the activation of inflammatory kinases (IKKβ, JNK and ERK) in the living cells and cell lysate. The kinase activation was blocked in the cells by ATP inhibition. CONCLUSIONS The data suggest that the pro- and anti-inflammatory cytokines are dynamically balanced in the white adipose tissue by iATP.