| First Author | Kenny S | Year | 2013 |
| Journal | Endocrinology | Volume | 154 |
| Issue | 2 | Pages | 718-26 |
| PubMed ID | 23254194 | Mgi Jnum | J:194605 |
| Mgi Id | MGI:5474399 | Doi | 10.1210/en.2012-1913 |
| Citation | Kenny S, et al. (2013) Gastric expression of plasminogen activator inhibitor (PAI)-1 is associated with hyperphagia and obesity in mice. Endocrinology 154(2):718-26 |
| abstractText | The adipokine plasminogen activator inhibitor (PAI)-1 is increased in plasma of obese individuals and exhibits increased expression in the stomachs of individuals infected with Helicobacter. To investigate the relevance of gastric PAI-1, we used 1.1 kb of the H(+)/K(+)beta subunit promoter to overexpress PAI-1 specifically in mouse gastric parietal cells (PAI-1-H/Kbeta mice). We studied the physiological, biochemical, and behavioral characteristics of these and mice null for PAI-1 or a putative receptor, urokinase plasminogen activator receptor (uPAR). PAI-1-H/Kbeta mice had increased plasma concentrations of PAI-1 and increased body mass, adiposity, and hyperphagia compared with wild-type mice. In the latter, food intake was inhibited by cholecystokinin (CCK)8s, but PAI-1-H/Kbeta mice were insensitive to the satiating effects of CCK8s. PAI-1-H/Kbeta mice also had significantly reduced expression of c-fos in the nucleus tractus solitarius in response to CCK8s and refeeding compared with wild-type mice. Exogenous PAI-1 reversed the effects of CCK8s on food intake and c-fos levels in the nucleus tractus solitarius of wild-type mice, but not uPAR-null mice. Infection of C57BL/6 mice with Helicobacter felis increased gastric abundance of PAI-1 and reduced the satiating effects of CCK8s, whereas the response to CCK8s was maintained in infected PAI-1-null mice. In cultured vagal afferent neurons, PAI-1 inhibited stimulation of neuropeptide Y type 2 receptor (Y2R) expression by CCK8s. Thus, gastric expression of PAI-1 is associated with hyperphagia, moderate obesity, and resistance to the satiating effects of CCK indicating a new role in suppressing signals from the upper gut that inhibit food intake. |
