Enhanced nutritionally induced adipose tissue development in mice with stromelysin-1 gene inactivation

To investigate a potential role of stromelysin-1 (MMP-3) in development of adipose tissue, 5 week old male MMP-3 deficient mice (MMP-3(-/-)) and wild-type (MMP-3(+/+)) controls were kept on a high fat diet (HFD) for 15 weeks. MMP-3(-/-) mice were hyperphagic and gained more weight than the MMP-3(+/+) mice. At the time of sacrifice, the body weight of the MMP-3(-/-) mice was significantly higher than that of the MMP-3(+/+) mice, as was the weight of the isolated subcutaneous (SC) and gonadal (GON) fat deposits. Significant adipocyte hypertrophy was observed in the GON but not in the SC adipose tissue of MMP-3(-/-) mice. Fasting plasma glucose and cholesterol levels were comparable in both genotypes, whereas triglyceride levels were significantly lower in MMP-3(-/-) mice. Staining with an endothelial cell specific lectin revealed a significantly higher blood vessel density and larger total stained area in the GON adipose tissues of MMP-3(-/-) mice. Thus, in a murine model of nutritionally induced obesity, MMP-3 impairs adipose tissue development, possibly by affecting food intake and/or adipose tissue-related angiogenesis.