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Characterization of age-related gene expression profiling in bone marrow and epididymal adipocytes.

Liu LF, Shen WJ, Ueno M, Patel S, Kraemer FB - BMC Genomics (2011)

Bottom Line: Age had a substantial effect on genes associated with mitochondria function and inflammation in bone marrow adipocytes.Twenty seven genes were significantly changed with age in both adipocyte depots.Among these genes, IL6 and GPR109A were significantly reduced with age in both adipocyte depots.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Endocrinology, Stanford University, CA 94305-5103, USA.

ABSTRACT

Background: While an increase in bone marrow adiposity is associated with age-related bone disease, the function of bone marrow adipocytes has not been studied. The aim of this study was to characterize and compare the age-related gene expression profiles in bone marrow adipocytes and epididymal adipocytes.

Results: A total of 3918 (13.7%) genes were differentially expressed in bone marrow adipocytes compared to epididymal adipocytes. Bone marrow adipocytes revealed a distinct gene profile with low expression of adipocyte-specific genes peroxisome proliferator-activated receptor gamma (PPARγ), fatty acid binding protein 4 (FABP4), perilipin (Plin1), adipsin (CFD) and high expression of genes associated with early adipocyte differentiation (CCAAT/enhancer binding protein beta (C/EBPβ), regulator of G-protein signaling 2 (RGS2). In addition, a number of genes including secreted frizzled related protein 4 (SFRP4), tumor necrosis factor α (TNFα), transforming growth factor beta 1(TGFβ1), G-protein coupled receptor 109A (GPR109A) and interleukin 6 (IL-6), that could affect adipose-derived signaling to bone are markedly increased in bone marrow adipocytes. Age had a substantial effect on genes associated with mitochondria function and inflammation in bone marrow adipocytes. Twenty seven genes were significantly changed with age in both adipocyte depots. Among these genes, IL6 and GPR109A were significantly reduced with age in both adipocyte depots.

Conclusions: Overall, gene profiling reveals a unique phenotype for primary bone marrow adipocytes characterized by low adipose-specific gene expression and high expression of inflammatory response genes. Bone marrow and epididymal adipocytes share a common pathway in response to aging in mice, but age has a greater impact on global gene expression in epididymal than in bone marrow adipocytes. Genes that are differentially expressed at greater levels in the bone marrow are highly regulated with age.

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Age-related gene expression in adipocytes. Heat maps of age-associated gene expression changes in bone marrow and epididymal white adipocytes. A. Clustering of genes involved in mitochondria function. B. Clustering of genes associated with lipolysis. C. Clustering of age-regulated genes in bone marrow and epididymal adipocytes.
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Figure 5: Age-related gene expression in adipocytes. Heat maps of age-associated gene expression changes in bone marrow and epididymal white adipocytes. A. Clustering of genes involved in mitochondria function. B. Clustering of genes associated with lipolysis. C. Clustering of age-regulated genes in bone marrow and epididymal adipocytes.

Mentions: We next sought to identify genes affected by aging within each adipocyte population based on ontology. Aging-related alterations of gene expression were identified and a list of genes was generated yielding a total of 5649 genes that displayed significant changes in both bone marrow and epididymal adipocytes with age. Analyses were conducted using two-way ANOVA including interaction of cell types and age. The comparisons were conducted by comparing 14-month-old and 18-month-old to 6-month-old. Genes were further analyzed by Ingenuity Pathway Analyses to relate age-associated gene expression changes to biological function and signaling pathways. Age-related gene changes in adipocytes fell into several categories of biological function including inflammatory response, genetic disorder and cellular development, whereas the majority of alterations of genes in both adipocyte depots were associated with mitochondrial dysfunction and lipid metabolism. Figure 4A shows that genes involved in fatty acid synthesis were increased with age in bone marrow adipocytes, including Acss1 (acyl-coA synthetase short chain family 1), Fads2 (fatty acid desaturase 2), and Slc27a4 (fatty acid transporter 4). Heat maps of age-altered genes in the bone marrow and epididymal adipocytes are indicated in Figure 5. Figure 5A illustrates age-related changes in genes involved in mitochondria function in which 18-month-old bone marrow adipocytes and epididymal adipocytes were most affected. Figure 5B displays the differential expression of genes involved in lipolysis in response to aging in both adipocyte populations. TNFα, Plin3 and Lipe (hormone sensitive lipase) increased in 14-month-old bone marrow adipocytes, whereas most of these genes decreased in 14-month-old epididymal adipocytes. PNPLA2 (ATGL) was decreased with age in both adipocyte depots. As shown in Table 4, pathways and networks associated with adipocyte differentiation, lipolysis and mitochondria function displayed significant changes with age in adipocytes. Approximately 60 percent of genes associated with adipocyte differentiation were significantly up-regulated in 14-month-old bone marrow adipocytes, whereas 70 percent of genes were down-regulated in 14-month-old epididymal adipocytes. A similar pattern was also observed in lipolysis pathways. In addition, a group of genes associated with mitochondria function was significantly regulated in bone marrow adipocytes with age, but not in epididymal adipocytes, as indicated in Table 4. Fold change values of genes involved in adipocyte differentiation, lipolysis and mitochondrial function are listed in Tables 5, 6 and 7.


Characterization of age-related gene expression profiling in bone marrow and epididymal adipocytes.

Liu LF, Shen WJ, Ueno M, Patel S, Kraemer FB - BMC Genomics (2011)

Age-related gene expression in adipocytes. Heat maps of age-associated gene expression changes in bone marrow and epididymal white adipocytes. A. Clustering of genes involved in mitochondria function. B. Clustering of genes associated with lipolysis. C. Clustering of age-regulated genes in bone marrow and epididymal adipocytes.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3113784&req=5

Figure 5: Age-related gene expression in adipocytes. Heat maps of age-associated gene expression changes in bone marrow and epididymal white adipocytes. A. Clustering of genes involved in mitochondria function. B. Clustering of genes associated with lipolysis. C. Clustering of age-regulated genes in bone marrow and epididymal adipocytes.
Mentions: We next sought to identify genes affected by aging within each adipocyte population based on ontology. Aging-related alterations of gene expression were identified and a list of genes was generated yielding a total of 5649 genes that displayed significant changes in both bone marrow and epididymal adipocytes with age. Analyses were conducted using two-way ANOVA including interaction of cell types and age. The comparisons were conducted by comparing 14-month-old and 18-month-old to 6-month-old. Genes were further analyzed by Ingenuity Pathway Analyses to relate age-associated gene expression changes to biological function and signaling pathways. Age-related gene changes in adipocytes fell into several categories of biological function including inflammatory response, genetic disorder and cellular development, whereas the majority of alterations of genes in both adipocyte depots were associated with mitochondrial dysfunction and lipid metabolism. Figure 4A shows that genes involved in fatty acid synthesis were increased with age in bone marrow adipocytes, including Acss1 (acyl-coA synthetase short chain family 1), Fads2 (fatty acid desaturase 2), and Slc27a4 (fatty acid transporter 4). Heat maps of age-altered genes in the bone marrow and epididymal adipocytes are indicated in Figure 5. Figure 5A illustrates age-related changes in genes involved in mitochondria function in which 18-month-old bone marrow adipocytes and epididymal adipocytes were most affected. Figure 5B displays the differential expression of genes involved in lipolysis in response to aging in both adipocyte populations. TNFα, Plin3 and Lipe (hormone sensitive lipase) increased in 14-month-old bone marrow adipocytes, whereas most of these genes decreased in 14-month-old epididymal adipocytes. PNPLA2 (ATGL) was decreased with age in both adipocyte depots. As shown in Table 4, pathways and networks associated with adipocyte differentiation, lipolysis and mitochondria function displayed significant changes with age in adipocytes. Approximately 60 percent of genes associated with adipocyte differentiation were significantly up-regulated in 14-month-old bone marrow adipocytes, whereas 70 percent of genes were down-regulated in 14-month-old epididymal adipocytes. A similar pattern was also observed in lipolysis pathways. In addition, a group of genes associated with mitochondria function was significantly regulated in bone marrow adipocytes with age, but not in epididymal adipocytes, as indicated in Table 4. Fold change values of genes involved in adipocyte differentiation, lipolysis and mitochondrial function are listed in Tables 5, 6 and 7.

Bottom Line: Age had a substantial effect on genes associated with mitochondria function and inflammation in bone marrow adipocytes.Twenty seven genes were significantly changed with age in both adipocyte depots.Among these genes, IL6 and GPR109A were significantly reduced with age in both adipocyte depots.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Endocrinology, Stanford University, CA 94305-5103, USA.

ABSTRACT

Background: While an increase in bone marrow adiposity is associated with age-related bone disease, the function of bone marrow adipocytes has not been studied. The aim of this study was to characterize and compare the age-related gene expression profiles in bone marrow adipocytes and epididymal adipocytes.

Results: A total of 3918 (13.7%) genes were differentially expressed in bone marrow adipocytes compared to epididymal adipocytes. Bone marrow adipocytes revealed a distinct gene profile with low expression of adipocyte-specific genes peroxisome proliferator-activated receptor gamma (PPARγ), fatty acid binding protein 4 (FABP4), perilipin (Plin1), adipsin (CFD) and high expression of genes associated with early adipocyte differentiation (CCAAT/enhancer binding protein beta (C/EBPβ), regulator of G-protein signaling 2 (RGS2). In addition, a number of genes including secreted frizzled related protein 4 (SFRP4), tumor necrosis factor α (TNFα), transforming growth factor beta 1(TGFβ1), G-protein coupled receptor 109A (GPR109A) and interleukin 6 (IL-6), that could affect adipose-derived signaling to bone are markedly increased in bone marrow adipocytes. Age had a substantial effect on genes associated with mitochondria function and inflammation in bone marrow adipocytes. Twenty seven genes were significantly changed with age in both adipocyte depots. Among these genes, IL6 and GPR109A were significantly reduced with age in both adipocyte depots.

Conclusions: Overall, gene profiling reveals a unique phenotype for primary bone marrow adipocytes characterized by low adipose-specific gene expression and high expression of inflammatory response genes. Bone marrow and epididymal adipocytes share a common pathway in response to aging in mice, but age has a greater impact on global gene expression in epididymal than in bone marrow adipocytes. Genes that are differentially expressed at greater levels in the bone marrow are highly regulated with age.

Show MeSH
Related in: MedlinePlus