Loss of CEACAM1 in hepatocytes causes hepatic fibrosis.

BACKGROUND: The role of insulin resistance in hepatic fibrosis in Metabolic dysfunction-Associated SteatoHepatitis (MASH) remains unclear. Carcinoembryonic Antigen-related Cell Adhesion Molecule1 protein (CEACAM1) promotes insulin clearance to maintain insulin sensitivity and repress de novo lipogenesis, as bolstered by the development of insulin resistance and steatohepatitis in AlbuminCre + Cc1fl/fl mice with liver-specific mouse gene encoding CEACAM1 protein (Ceacam1) deletion. We herein investigated whether these mice also developed hepatic fibrosis and whether hepatic CEACAM1 is reduced in patients with MASH at different fibrosis stages. METHODS: AlbuminCre + Cc1fl/fl mice were fed a regular or a high-fat diet before their insulin metabolism and action were assessed during IPGTT, and their livers excised for histochemical, immunohistochemical and Western blot analysis. Sirius red staining was used to assess fibrosis, and media transfer was employed to examine whether mutant hepatocytes activated hepatic stellate cells (HSCs). Hepatic CEACAM1 protein levels in patients with varying disease stages were assessed by ELISA. RESULTS: Hepatocytic deletion of Ceacam1 caused hyperinsulinemia-driven insulin resistance emanating from reduced hepatic insulin clearance. AlbuminCre + Cc1fl/fl livers showed inflammation, fibrosis and hepatic injury, with more advanced bridging and chicken-wire hepatic fibrosis under high-fat conditions. Media transferred from hepatocytes isolated from mutant mice activated control HSCs, likely owing to their elevated endothelin1 content. Interestingly, hepatic CEACAM1 levels were lower in the livers of patients with MASH and declined gradually with advanced fibrosis stage. CONCLUSIONS: Hepatic CEACAM1 levels declined with progression of MASH in humans. The phenotype of AlbuminCre + Cc1fl/fl mice assigned a key role to CEACAM1 loss from hepatocytes in hepatic fibrosis independently of other liver cells.

Development and Relative Validity of the Chronic Kidney Disease Short Food Frequency Questionnaire (CKD SFFQ) to Determine Diet Quality and Dietary Habits among Adults with Chronic Kidney Disease.

Limited instruments are available to determine diet quality among US adults with chronic kidney disease (CKD). The purpose of this study was two-fold: (1) to develop a food frequency questionnaire, CKD SFFQ, for adults with CKD and (2) to validate the CKD SFFQ against two 24-h recalls in determining diet quality (DQ). A 57-item CKD SFFQ was developed through a content validation method. Adults with CKD (n = 46) completed the CKD SFFQ and 2-24-h recalls. Statistical analyses included descriptive statistics, frequencies, t-tests, Pearson correlations, and Bland-Altman plots. All data were analyzed using JMP SAS v15 with statistical significance detected at p < 0.05. Results showed no differences for the overall DQ (p = 0.11) and the nine whole-food components (p = 0.07 to p = 0.44) when comparing the CKD SFFQ to the 2-24-h recalls. Pearson correlation coefficients ranged from -0.39 (refined grains) to 0.60 (greens and beans). Bland-Altman plots showed overall good agreement and there was a systematic trend towards higher estimates with the CKD SFFQ, particularly for overall DQ, total proteins, and dairy. The majority of participants rarely or never consumed grains, fruits, vegetables, seafood, and plant proteins. The CKD SFFQ was demonstrated to be an acceptable method to determine DQ for adults with CKD.