Evaluation of body mass index, ponderal index, visceral cross-sectional area, subcutaneous fat cross-sectional area, and liver volume as predictive factors for obesity-related comorbidities: a retrospective cohort study.

BACKGROUND: The body mass index (BMI) is an imperfect clinical measure of obesity that should be used in conjunction with other valid measures of weight-related risk. We studied whether there is a superior measure of obesity-related comorbidities. METHODS: Records of bariatric clinic patients who had an abdominal computed tomography (CT) within 1 year of visit were reviewed. The presence of obesity-related comorbidities was determined at the time of the scan. BMI and ponderal index (PI) were calculated, and CT scans were reviewed to determine the visceral cross-sectional area (VCSA), subcutaneous fat cross-sectional area (SFCSA), and liver volume (LV). Data were analyzed using the Kruskal-Wallis test and Mann-Whitney U test. RESULTS: A higher number of comorbidities were found to be associated with a larger BMI (P = .011), VCSA (P = .014), SFCSA (P = .007), and LV (P = .014), but not a larger PI (P = .11). Of the 16 comorbidities assessed, VCSA and LV were associated with more than BMI and SFCSA. However, each measure could be associated with different comorbidities. A higher BMI was associated with increased insulin use (P = .034), hypertension (P = .007), and history of obstructive sleep apnea (P = .015), none of which were associated with PI. BMI and PI were the only measures associated with a history of deep vein thrombosis/pulmonary embolism (both P < .01). Only SFCSA was found to be associated with gastroesophageal reflux disease (P = .029). VCSA (P = .038) and LV (P = .001) were associated with nonalcoholic fatty liver disease. CONCLUSION: No measure could account for all obesity-related comorbidities, implying the need for targeted measurements. However, PI was the least effective measure.

Loss of NKCC1 function increases epithelial tight junction permeability by upregulating claudin-2 expression.

Conditions that cause the loss of epithelial barrier integrity are often accompanied by dysregulation of tight junction protein expression and/or localization. Recently, we have reported that patients with mutations in SLC12A2, the gene encoding the basolateral Na+-K+-2Cl- cotransporter (NKCC1), suffer from severe gastrointestinal deficits, including chronic gastrointestinal inflammation, gastrointestinal hemorrhage, intestinal obstruction, and constipation. Although the intestinal inflammation observed in patients with loss of NKCC1 function may or may not be due to tight junction dysfunction, we investigated whether the loss of NKCC1 function affects paracellular ion transport and epithelial barrier function. Wild-type HT29-MTX-E12 and CRISPR/Cas9-mediated NKCC1 knockout (KO) HT29 clones were tested for tight junction protein expression and localization. Tightness of epithelial cell monolayer was assessed by measurement of transepithelial electrical resistance and permeability of molecular tracers in transwell filters. Tight junction protein localization was assessed by immunofluorescence. Loss of NKCC1 expression strongly increases the expression of claudin-2 and occludin in epithelial cell monolayers. Loss of NKCC1 significantly reduces the transepithelial electrical resistance (TER) indicating an increase in paracellular ions flux, consistent with upregulation of the cation-selective and channel-forming claudin-2. In addition, NKCC1-KO monolayers showed a significant increase in the paracellular flux of small molecules like fluorescein (0.33 kDa), whereas the permeability of higher molecular weight TRITC-Dextran (4 kDa and 70 kDa) remained unchanged. Thus, NKCC1 regulates tight junction protein expression and loss of NKCC1 function affects epithelial barrier integrity.