Pancreas-specific lipase and lipase activity measured by immunological assays (Spec cPL and Spec fPL) and colorimetric assays (1,2-o-dilauryl-rac-glycelo-3-glutaric acid-(6'-methylresorufin) ester [DG Show more
Pancreas-specific lipase and lipase activity measured by immunological assays (Spec cPL and Spec fPL) and colorimetric assays (1,2-o-dilauryl-rac-glycelo-3-glutaric acid-(6'-methylresorufin) ester [DGGR] and triolein), respectively, are used to diagnose pancreatitis in both dogs and cats. However, DGGR and triolein assays may be influenced by extrapancreatic lipases, including hepatic triglyceride lipase (HTGL) and lipoprotein lipase (LPL). To investigate the effect of extrapancreatic lipases on immunological and colorimetric assays by measuring changes in HTGL and LPL activity following heparin administration. Six healthy Beagles and six adult purpose-bred cats were enrolled. HTGL and LPL activities were induced by intravenous heparin administration. Serum samples were collected at baseline and at 5-, 10-, 15-, and 60-min following heparin injection. Spec cPL, Spec fPL, and lipase activities were measured using DGGR and triolein assays, whereas HTGL and LPL activities were measured using their respective assays. Spec cPL and Spec fPL levels showed no significant changes following heparin administration. Conversely, DGGR-based and triolein-based lipase activities, as well as HTGL and LPL activities, were significantly increased after heparin administration in both dogs and cats. HTGL and LPL activities showed significant positive correlations with DGGR-based (P < .001, r = .90 for both) and triolein-based (P < .001, r = .63 and P < .001, r = .68, respectively) lipase activities, but not with Spec cPL and Spec fPL. DGGR- and triolein-based lipase activities are influenced by HTGL and LPL activities, as their substrates are hydrolyzed by pancreatic lipase, HTGL, and LPL. Show less
Liver X receptors (LXRs) monitor endogenous sterol levels to maintain whole-body cholesterol levels and regulate inflammatory responses. Recent studies have demonstrated that LXRs may inhibit cellular Show more
Liver X receptors (LXRs) monitor endogenous sterol levels to maintain whole-body cholesterol levels and regulate inflammatory responses. Recent studies have demonstrated that LXRs may inhibit cellular proliferation, but the underlying mechanism remains unclear. Cell cycle and apoptosis regulator 2 (CCAR2), previously known as DBC1/KIAA1967, is a transcriptional regulator that regulates cellular proliferation and energy metabolism by inhibiting sirtuin 1 (SIRT1) deacetylase. Based on the findings that CCAR2 regulates several nuclear receptors, including the estrogen receptors and androgen receptor, we aimed to identify the underlying mechanism of CCAR2 regulation of LXRα. We found that CCAR2 formed a complex with LXRα in a ligand-independent manner in HepG2 cells, and in vitro pull-down assays, it revealed a direct interaction between the amino terminus of CCAR2 and the AF-2 domain of LXRα. Thereby, CCAR2 attenuates the ligand-dependent transcriptional activation function of LXRα. RNA interference-mediated depletion of endogenous CCAR2 potentiated the expression of the LXRα target genes ATP-binding cassette transporter A1 and G1, and the abrogation of CCAR2 resulted in decreased cellular proliferation. Moreover, competitive immunoprecipitation studies revealed that the LXRα downregulation involves the inhibition of SIRT1-LXRα complex formation. Therefore, these results clearly indicate a novel mechanism in which CCAR2 may regulate the transcriptional activation function of LXRα due to its specific inhibition of SIRT1 and serve to regulate cellular proliferation. Show less