Loss of skeletal muscle mass (sarcopenia) is a major contributor to disability in old age. We used two-dimensional gel electrophoresis and mass spectrometry to screen for changes in proteins, and cDNA profiling to assess transcriptional regulations in the gastrocnemius muscle of adult (4 months) and aged (30 months) male Sprague-Dawley rats. Thirty-five proteins were differentially expressed in aged muscle. Proteins and mRNA transcripts involved in redox homeostasis and iron load were increased, representing novel components that were previously not associated with sarcopenia. Tissue iron levels were elevated in senescence, paralleling an increase in transferrin. Proteins involved in redox homeostasis showed a complex pattern of changes with increased SOD1 and decreased SOD2. These results suggest that an elevated iron load is a significant component of sarcopenia with the potential to be exploited clinically, and that mitochondria of aged striated muscle may be more vulnerable to radicals produced in cell respiration.

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...

The SOCS (suppressors of cytokine signaling) proteins have been suggested to function as inhibitors of cytokine receptor signaling. We have analyzed SOCS-2, SOCS-3, and CIS expression in relation to GH actions in the rat. SOCS-2, SOCS-3, and CIS transcripts were detected in various GH responsive tissues, including liver, muscle, and fat. In addition to the finding that different tissues express different levels of SOCS-2, SOCS-3, and CIS messenger RNA (mRNA), the steady-state levels of these SOCS transcripts were dependent on the endocrine status of the animal. SOCS-3 expression was 5-fold higher in fat from old compared with younger rats. Hypophysectomy reduced the levels of SOCS-2 and CIS mRNA in liver, muscle, and fat, whereas SOCS-3 expression was unchanged. Using primary cultures of rat hepatocytes, GH was shown to increase SOCS-2, SOCS-3, and CIS mRNA levels with different kinetics. SOCS-3 was rapidly and transiently induced, whereas SOCS-2 and CIS were increased in a slower fashion. Glucocorticoids blocked GH-induced SOCS-3 expression in cultured hepatocytes, whereas SOCS-2 and CIS expression was potentiated. Our data fit well with a concept of SOCS proteins acting as modulators of GH signal transduction.

The aim of this study was to identify genes for hepatic fuel metabolism with a gender-differentiated expression and to determine which of these that might be regulated by the female-specific secretion of GH. Effects of gender and continuous infusion of GH to male rats were studied in the liver using cDNA microarrays representing 3200 genes. Sixty-nine transcripts displayed higher expression levels in females, and 177 displayed higher expression in males. The portion of GH-regulated genes was the same (30%) within the two groups of gender-specific genes. The male liver had a higher expression of genes involved in fuel metabolism, indicating that male rats might have a greater capacity for high metabolic turnover, compared with females. Most notable among the female-predominant transcripts was fatty acid translocase/CD36, with 18-fold higher mRNA levels in the female liver and 4-fold higher mRNA levels in males treated with GH, compared with untreated males. This gender-differentiated expression was confirmed at mRNA and protein levels in the rat and at the mRNA level in human livers. Although purely speculative, it is possible that higher levels of fatty acid translocase/CD36 in human female liver might contribute to the sexually dimorphic development of diseases resulting from or characterized by disturbances in lipid metabolism, such as arteriosclerosis, hyperlipidemia, and insulin resistance.

The mechanisms that control life span and age-related phenotypes are not well understood. It has been suggested that aging or at least some of its symptoms are related to a physiological decline in GH levels with age. To test this hypothesis, and to improve our understanding of the cellular and molecular mechanisms behind the aging process, we have analyzed age-induced changes in gene expression patterns through the application of DNA chip technology. In the present study, the aging process was analyzed in rat liver in the presence or absence of GH replacement. Out of 3,000 genes printed on the microarrays, approximately 1,000 were detected in the rat liver. Among these, 47 unique transcripts were affected by the aging process in male rat livers. The largest groups of age-regulated transcripts encoded proteins involved in intermediary metabolism, mitochondrial respiration, and drug metabolism. Approximately 40% of the differentially expressed gene products were normalized after GH treatment. The majority of those transcripts have previously not been shown to be under GH control. The list of gene products that showed normalized expression levels in GH-treated old rats may shed further insight on the action and mechanism behind the positive effects of GH on, for example, fuel metabolism and body composition observed in different animal and human studies.