Regulation of collagen gene expression in 3T3-L1 cells. Effects of adipocyte differentiation and tumor necrosis factor .alpha.

Abstract

An early feature in the development of adipocytes from fibroblast-like precursor cells is the biogenesis of an extracellular basement membrane (Napolitano, 1963; Kuri-Harcuch et al., 1984). Interactions between components of the basement membrane (e.g., collagens) and the surfaces of differentiating adipocytes are thought to regulate subsequent phases of the developmental program. Since fibroblasts principally secrete type I and III collagens whereas type IV collagen is abundant in basement membrane, it appears that a switch in collagen gene expression is a key element in adipocyte differentiation. Little is known about the mechanisms underlying differentiation-dependent changes in collagen expression or the effects of the potent lipolytic cytokine TNF-alpha on collagen mRNA accumulation in preadipocytes and adipocytes. In this study, 3T3-L1 preadipocytes were found to express mRNAs encoding type I, III, and IV procollagens. When 3T3-L1 cells were stimulated to differentiate into adipocytes, the relative concentrations of type I and type III procollagen mRNAs declined by 80-90%. Parallel decreases in the rates of transcription of the procollagen I and procollagen III genes appear to account for the diminished levels of these mRNAs. In contrast, the relative rate of transcription of the procollagen IV gene increased 2.6-fold during adipocyte development. As a consequence, the abundance of type IV procollagen transcripts was elevated in adipocytes. Tumor necrosis factor alpha (TNF-alpha) is a cytokine that stimulates lipolysis, an apparent "dedifferentiation" of adipocytes, and inhibits transcription of certain adipocyte-specific genes. The effects of TNF-alpha on collagen mRNA levels were dependent upon the state of differentiation of 3T3-L1 cells.(ABSTRACT TRUNCATED AT 250 WORDS)

The adipose conversion process: regulation by extracellular and intracellular factors

“…This hormonal agent could act in an autocrine/paracrine manner since it is locally produced by porcine adipocytes in vivo and in vitro [184]. Consistently with its inhibitory effect, its synthesis is decreased during the adipose conversion of 3T3-L1 cells [254]. Finally, TGFβ can also reduce the expression of adipose genes in mature adipocytes [240].…”

“…It can act directly on lipid metabolism by decreasing FA uptake (e.g., decrease in LPL, FAT and FATP expression) and lipogenesis (e.g., decrease in FAS and ACC expression), and by increasing lipolysis [205]. Indirect effects have also been observed since this cytokine can alter collagen (types I, III, and IV) and β-actin synthesis in 3T3-L1 cells [254]. These authors also showed that TNFα could exert its effect by increasing the TGFβ mRNA content.…”

Col1a1 Promoter-targeted Expression of p20 CCAAT Enhancer-binding Protein β (C/EBPβ), a Truncated C/EBPβ Isoform, Causes Osteopenia in Transgenic Mice

“…COL1A1 expression is extinguished during adipocyte differentiation and is not expressed in mature adipocytes (27)(28)(29)(30). Therefore, if dominant negative inhibition by p20C/EBP␤ is incomplete in adipocyte progenitors, residual C/EBP activation could promote entry of these cells into the adipogenic program, causing extinction of transgene expression and unimpeded terminal adipocyte differentiation.…”

Differential Regulation by Tumor Necrosis Factor-α of β1-, β2-, and β3-Adrenoreceptor Gene Expression in 3T3-F442A Adipocytes

“…*, p Ͻ 0.05; **, p Ͻ 0.001, TNF-␣-treated versus control adipocytes. Exposure to TNF-␣ has been demonstrated to cause a suppression of fat cell gene expression and, in some cases, a dedifferentiation of 3T3-L1 adipocytes (13,37), TA1 adipocytes (3), or human preadipocytes in culture (6). This effect of TNF-␣ on the differentiation process has been related to its inhibitory action on transcription factors that trigger adipogenesis, like C/EBP-␣ (13,14,38,39) or PPAR-␥ (40).…”