The effect of obesity and tobacco smoke exposure on inflammatory mediators and matrix metalloproteinases in rat model

Obesity is characterized by hypertrophy of adipose tissue and chronic obstructive pulmonary disease (COPD) by lung damage; both diseases are associated with systemic low-grade inflammation. There are no animal models combining obesity and COPD; therefore, these diseases were induced simultaneously in rats to analyze their effects on the expression of inflammatory mediators and enzymes involved in lung tissue remodeling. Obesity was induced with sucrose (30%) for 4 months concomitant with tobacco smoke exposure (20 cigarettes/day, 5 days/wk) for the last 2 months. Were evaluated: body weight, abdominal fat, dyslipidemia, glucose tolerance test (GTT), histology, inflammatory mediators with qPCR and enzyme-linked immunosorbent assay, matrix metalloproteinases (MMP-2), MMP-9, MMP-12, TIMP-1 and TIMP-2 through qRT-PCR, and MMP-2 and MMP-9 by gelatin zymography. The rats on a sucrose diet exhibited increased body weight, abdominal fat, triglycerides, GTT, and plasma levels of insulin, adiponectin, leptin, resistin, IL-6, IL-1 beta, tumor necrosis factor-alpha (TNF-alpha) and IFN-gamma, upregulated lung IL-6, IL-1 beta, TNF-alpha and IFN-gamma, showing hyperplastic bronchial and alveolar epithelium. The animals exposed to sucrose and tobacco smoke exhibited decreased body weight, abdominal fat and plasma levels of leptin, resistin, IL-1 beta and IFN-gamma, reducing inflammation but showing emphysematous lesions. Expression of gelatinases and MMP-12 augmented in the rats exposed to tobacco smoke alone or combined with sucrose. Zymography showed prominent gelatinases activity in all the experimental groups. These results suggest that simultaneous exposure to sucrose and tobacco smoke decreases inflammation but results in emphysematous lesions similar to those observed with tobacco smoke exposure, suggesting that obesity does not confer any protective effect against lung damage.