An alternative model for studying age-associated metabolic complications: Senescence-accelerated mouse prone 8

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Abstract

Rodent animal models take at least 18 months to develop aging phenotypes for researchers to investigate the mechanism of age-related metabolic complications. Senescence-accelerated mouse prone 8 (SAMP8) shortens the process of aging and may facilitate an alternative model for studying age-related insulin resistance. The short-lived strain SAMP8 and two long-lived strains SAM resistant 1 (SAMR1) mice and C57BL/6 mice at 12 (young) and 40 weeks old (old) were used in the present study. Glucose tolerance test, histology and signaling pathways involved in lipid metabolism in adipose tissue and liver and key components of insulin signaling pathway in the skeletal muscle were determined in these three strains. We found that short-lived SAMP8 mice developed symptoms of insulin resistance including hyperglycemia, hyperinsulinemia, and impaired glucose tolerance in association with adipocyte hypertrophy and ectopic lipid accumulation in liver and muscle at 40-wk.-old. Significantly increased serum IL-6, leptin, and resistin levels and adipogenic transcription factor PPARγ and macrophage marker F4/80 mRNA expression in adipose tissues were observed in old SAMP8 mice, compared with that in young SAMP8 mice. Marked increases in SREBP1 and PPARγ and a decrease in PPARα at mRNA level in accordance with activation of mTOR/Akt pathway were contributed to hepatic lipid accumulation in old SAMP8 mice. Down-regulation of insulin signaling pathway including IRβ, IRS1, and AS160 at protein level in skeletal muscle was observed in old SAMP8 mice. At 40-wk.-old, both long-lived SAMR1 and C57BL/6 mice have not been fully developed age-related metabolic disorders including insulin resistance and visceral fat expansion in line with fewer defects in lipid metabolism and skeletal muscle insulin signaling pathway. In conclusion, our data suggest the suitability of the SAMP8 mice as a model for studying age-related metabolic complications.

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