Effects of a palmitate and fructose rich diet on lung fibrosis and inflammation markers in a murine model

Abstract

Palmitic acid (PA)-rich diet might promote idiopathic pulmonary fibrosis (IPF). A link between SFA intake and IPF is suggested because: 1) IPF lungs present a high PA content in surfactant phospholipids; 2) saturated fatty acids (SFA) intake positively correlated with IPF incidence, and 3) high-fat diet worsens bleomycin (BLM)-induced pulmonary fibrosis (PF). Moreover, a high intake in simple carbohydrates has been suggested as a risk factor. Here, the aim is to assess the potential lung profibrotic effect of a PA- and fructose-rich diet in mice. Young (2-4 m.o.) and aged (18-20 m.o.) female mice were exposed to a PA-rich diet and 10% fructose in water (PAF) for 9 weeks. Control groups were fed standard chow and water. As a PF model, adult mice were instilled with 6 U/kg BLM. Body weight and glycaemia were periodically assessed. Bronchoalveolar lavage fluid (BALF) cell populations were analysed by flow cytometry. Profibrotic and proinflammatory markers were determined by PCR and western blot. PAF diet increased body weight in young (p=0,03) and aged (p<0,0001) mice, and blood sugar in young mice (p=0,002) to PAF-fed aged mice levels. Age increased BALF lymphocyte count (p=0,04) and decreased granulocyte count (p=0,01). PAF diet decreased granulocyte count (p=0,01) mimicking the effect of BLM (p=0,001). Lung Il-6 mRNA was induced (p=0,04) in response to PAF diet, while Acta2 tended to increase (p=0,14). BLM induced Fn1 mRNA and PAF-fed aged mice showed similar levels. Chronic exposure to PAF diet triggered proinflammatory effects and a profibrotic state in lungs. These results support the hypothesis that certain dietary habits might contribute to PF development.