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Adipose tissue-derived tumor necrosis factor-alpha activity is elevated in older rats
C L Morin1, M J Pagliassotti, D Windmiller
1Division of Endocrinology, Metabolism, and Diabetes, University of Colorado, Denver, USA. Catherine.Morin@UCHSC.EDU
Summary
Adipose tissue-derived tumor necrosis factor-alpha (AT-TNF) activity increases with age in rats, correlating with larger fat cells. This suggests age-related changes in AT-TNF activity, not just levels, are important.
Area of Science:
- Metabolic research
- Endocrinology
- Adipose tissue biology
Background:
- High adipose tissue-derived tumor necrosis factor-alpha (AT-TNF) mRNA and protein are linked to obesity and insulin resistance.
- Endogenous TNF inhibitors exist, but it's unclear if AT-TNF activity increases with age.
- Fat mass accumulation is expected in older animals, potentially increasing AT-TNF activity.
Purpose of the Study:
- To investigate if AT-TNF activity increases in older Fischer 344 rats due to increased fat mass.
- To compare AT-TNF activity, protein, and mRNA levels between young and mature rats.
- To explore the relationship between AT-TNF activity, insulin resistance, and adipose cell size.
Main Methods:
- Comparison of 3-month-old (young) and 14-month-old (mature) male Fischer 344 rats.
- Measurement of fat mass, fasting plasma insulin, and AT-TNF activity in epididymal and retroperitoneal fat pads.
- Analysis of AT-TNF protein and mRNA, along with mRNA for lipoprotein lipase, hormone-sensitive lipase, and Glut4.
Main Results:
- Mature rats had 1.5-fold more fat mass but similar fasting plasma insulin levels compared to young rats.
- AT-TNF activity was doubled in mature rats in both fat pads (p < .0005).
- AT-TNF activity strongly correlated with adipose cell size (r = .79-.81, p < .0001) and fasting insulin in retroperitoneal fat (r = .48, p = .04).
- AT-TNF protein levels were higher in young rats, suggesting potential inhibitor presence in older rats.
- No significant differences in AT-TNF mRNA or key metabolic gene mRNA were observed between age groups.
Conclusions:
- Adipose tissue-derived tumor necrosis factor-alpha (AT-TNF) activity increases in mature rats, correlating with increased adipose cell size.
- Younger rats may have higher AT-TNF protein levels due to the presence of an inhibitor affecting activity.
- Age-related increases in AT-TNF activity, rather than just mRNA or protein levels, may be significant in metabolic changes.