BACKGROUND: The regulatory gene pathways that accompany loss of adipose tissue in cancer cachexia are unknown and were explored using pangenomic transcriptome profiling. METHODS: Global gene expression profiles of abdominal subcutaneous adipose tissue were studied in gastrointestinal cancer patients with (n ¼ 13) or without (n ¼ 14) cachexia. RESULTS: Cachexia was accompanied by preferential loss of adipose tissue and decreased fat cell volume, but not number. Adipose tissue pathways regulating energy turnover were upregulated, whereas genes in pathways related to cell and tissue structure (cellular adhesion, extracellular matrix and actin cytoskeleton) were downregulated in cachectic patients. Transcriptional response elements for hepatic nuclear factor-4 (HNF4) were overrepresented in the promoters of extracellular matrix and adhesion molecule genes, and adipose HNF4 mRNA was downregulated in cachexia. CONCLUSIONS: Cancer cachexia is characterised by preferential loss of adipose tissue; muscle mass is less affected. Loss of adipose tissue is secondary to a decrease in adipocyte lipid content and associates with changes in the expression of genes that regulate energy turnover, cytoskeleton and extracellular matrix, which suggest high tissue remodelling. Changes in gene expression in cachexia are reciprocal to those observed in obesity, suggesting that regulation of fat mass at least partly corresponds to two sides of the same coin.
Macronutrients have a secondary role in changes in adipocyte gene expression after energy-restricted diets. The most striking alteration after energy restriction is a coordinated reduction in the expression of genes regulating the production of polyunsaturated fatty acids.
There is growing evidence that the distribution of adipose tissue in the body is of importance in the development of metabolic complications of obesity, such as diabetes, hypertension, and hyperlipidemia. The aim of this study was to identify differentially expressed genes in subcutaneous and omental human adipose tissue in obese men, using a subtractive hybridization strategy. From the obtained set of differentially expressed transcripts, we also aimed to identify genes that have a sex-specific pattern of expression in omental or subcutaneous adipose tissue. Representational difference analysis (RDA) was performed on cDNA from subcutaneous and omental fat tissue from a man with extreme abdominal obesity. Forty-four putatively differentially expressed genes were identified. The obtained RDA products were spotted onto glass slides to screen for differential expression in other obese patients by using a microarray hybridization procedure. Five genes were confirmed to be differentially expressed in subcutaneous or omental adipose tissue from male or female obese patients. One gene was detected only in males and was found to be upregulated in subcutaneous tissue. The findings extend previous knowledge that different fat depots have differential gene expression and indicate that sex differences exist in adipose gene expression patterns. Linder, K., P. Arner, A. It is well established that accumulation of visceral fat is associated with a higher risk for development of obesityrelated diseases such as type 2 diabetes, cardiovascular disease, hypertension, and hyperlipidemia (1). Adipose tissue distribution differs between men and women, and visceral obesity is much more common among men than women (2, 3). The metabolic and endocrine functions of adipose tissue from various depots differ in a way that may explain the association of visceral but not subcutaneous fat with obesity-related cardiovascular and metabolic problems (4).Regarding the metabolic function of fat, visceral adipose tissue is more sensitive to the stimulation of lipolysis by cathecolamines, whereas subcutaneous fat is more sensitive to the antilipolytic effects of insulin. Concerning endocrine function, visceral and subcutaneous adipocytes have different capacities to produce hormones and enzymes. Depot-related variation in mRNA expression has been shown for several genes, including leptin, TNF-␣ , angiotensinogen, PAI-1 (4), and recently, carboxypeptidase E and thrombospondin-1 (5).The mechanisms responsible for depot differences in adipose function are unknown. It is possible that fat cells in various regions have different origins and, because of this, express different genes. Recent indirect evidence supports this idea, because newly formed adipocytes in human subcutaneous and visceral fat were shown to maintain the phenotypic site differences of mature adipocytes (6).The major aim of the present study was to determine differences in gene expression patterns between subcutaneous and omental adipose tissue. We have used representational dif...
Follistatin is a new adipokine important for adipogenesis. Down-regulated WAT expression of follistatin in obesity may counteract adiposity but could, by inhibiting adipogenesis, contribute to hypertrophic obesity (large fat cells) and insulin resistance.
The pathogenesis of male osteoporosis at the cellular level is still elusive. We performed histomorphometric analysis of bone biopsy samples from 51 eugonadal men with idiopathic osteoporosis. Their median age was 54 (range 29-73) years. Eighty-two percent of the patients had a fracture history, and 57% had vertebral fractures. Bone volume, trabecular thickness, wall thickness, and osteoid thickness were significantly reduced in osteoporotic men compared with healthy men. Erosion depth was similar, as were the bone remodeling parameters such as bone formation rate, mineral apposition rate, and activation frequency. In the osteoporotic men, osteoid thickness was correlated to bone mineral density at the lumbar spine (R(2) = 0.19, P < 0.01); together with wall thickness, the two parameters could explain 27% of the variation in lumbar spine bone mineral density. The osteoid thickness was correlated to anthropometric variables such as body weight (R(2) = 0.24, P < 0.001) and body mass index (R(2) = 0.14, P < 0.01), as well as to serum estradiol levels (R(2) = 0.14, P < 0.01) and to the ratio insulin-like growth factor-1 (IGF-1) to IGF-binding protein-1 (IGFBP-1) (R(2) = 0.12, P < 0.01). Regression analysis showed that 36% of the variation in osteoid thickness could be predicted by body weight and estradiol levels. In conclusion, bone histomorphometry in male idiopathic osteoporosis was characterized by thin bone structural units, which might suggest osteoblast dysfunction. Bone histomorphometry parameters were associated with low body weight, low estradiol levels, and increased levels of IGFBP-1, supporting the notion that estrogens and IGFs play regulatory roles in male bone turnover.
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