| Popis: |
White adipose tissue (WAT) produces many hormones and cytokines with various functions, such as glucose homeostasis, inflammation, and hemostasis, among others. The contributions of individual WAT depots to these functions differ, such that intra-abdominal depots correlate more closely than subcutaneous depots with obesity-related disorders (insulin resistance, type 2 diabetes, cardiovascular disease, etc.). However, the molecular mechanisms behind these depot-specific differences and their relation to age are not well understood. Growth hormone receptor gene-disrupted (GHR-/-) mice are dwarf and display enhanced insulin sensitivity and prolonged longevity in spite of obesity. The accumulation of WAT in GHR-/- mice is mainly in subcutaneous depots; thus, these mice represent a useful tool to study depot-specific effects on insulin responsiveness and lifespan. To analyze depot- and age-related differences in protein expression in WAT depots of GHR-/- and wild-type mice, four WAT depots (inguinal, retroperitoneal, mesenteric, and epididymal) of 12 and 24-month-old male mice of each genotype were resolved by two-dimensional gel electrophoresis and subsequent mass spectrometry. Comparisons among wild-type WAT depots showed differences in the levels of many proteins, including metabolic enzymes and stress-resistant proteins that were higher in epididymal and mesenteric depots and lower in inguinal (subcutaneous) WAT. Also, several protein levels were consistent with higher vascularization in mesenteric WAT than in the other depots. On the other hand, age-related changes in WAT depots suggested higher aerobic glucose oxidation, lipolysis and oxidative damage at old age. Interestingly, depot- and age-related variations in protein levels were similar between wild-type and GHR-/- mice. However, genotype differences were found in the expression of proteins related to senescence and glucose uptake, among others. In conclusion, WAT depots display marked differences in their proteomes that are affected similarly with advancing age (e.g. increased insulin resistance and oxidative damage). In addition, altered senescence-related processes in WAT depots of GHR-/- mice may contribute to the favorable phenotype observed in these animals. Our results provide valuable information about WAT physiology in different depots and ages of wild-type and GHR-/- mice. Specific proteins shown to vary in this study may represent targets for treatment of age-associated insulin resistance, oxidative damage, and other WAT-related pathologies. |
