| First Author | Bederman I | Year | 2012 |
| Journal | Am J Physiol Gastrointest Liver Physiol | Volume | 303 |
| Issue | 4 | Pages | G507-18 |
| PubMed ID | 22679004 | Mgi Jnum | J:191611 |
| Mgi Id | MGI:5462162 | Doi | 10.1152/ajpgi.00451.2011 |
| Citation | Bederman I, et al. (2012) Altered de novo lipogenesis contributes to low adipose stores in cystic fibrosis mice. Am J Physiol Gastrointest Liver Physiol 303(4):G507-18 |
| abstractText | Cystic fibrosis (CF) mouse models exhibit exocrine pancreatic function, yet they do not develop adipose stores to the levels of non-CF mice. CF mice homozygous for the Cftr mutation (F508del) at 3 wk (postweaning) and 6 wk (young adult) of age had markedly less adipose tissue than non-CF mice. Food intake was markedly lower in 3-wk-old CF mice but normalized by 6 wk of age. Both 3- and 6-wk-old mice had dietary lipid absorption and fecal lipid excretion comparable to non-CF mice. Hepatic de novo lipogenesis (DNL), determined by (2)H incorporation, was reduced in CF mice. At 3 wk, F508del mice had significantly decreased DNL of palmitate and stearate, by 83% and 80%, respectively. By 6 wk, DNL rates in non-CF mice remained unchanged compared with 3-wk-old mice, while DNL rates of F508del mice were still reduced, by 33% and 40%, respectively. Adipose tissue fatty acid (FA) profiles were comparable in CF and non-CF mice, indicating that adipose differences are quantitative, not qualitative. A correspondingly lower content of (2)H-labeled FA was found in CF adipose tissue, consistent with reduced deposition of newly made hepatic triglycerides and/or decreased adipose tissue lipogenesis. Hepatic transcriptome analysis revealed lower mRNA expression from several genes involved in FA biosynthesis, suggesting downregulation of this pathway as a mechanism for the reduced lipogenesis. These novel data provide a model for altered lipid metabolism in CF, independent of malabsorption, and may partly explain the inability of pancreatic enzyme replacement therapy to completely restore normal body mass to CF patients. |
