Genetic and Functional Characterization of Novel Brown-Like Adipocytes Around the Lamprey Brain.

During the process of vertebrate evolution, many thermogenic organs and mechanisms have appeared. Mammalian brown adipose tissue (BAT) generates heat through the uncoupling oxidative phosphorylation of mitochondria, acts as a natural defense against hypothermia and inhibits the development of obesity. Although the existence, cellular origin and molecular identity of BAT in humans have been well studied, the genetic and functional characteristics of BAT from lampreys remain unknown. Here, we identified and characterized a novel, naturally existing brown-like adipocytes at the lamprey brain periphery. Similar to human BAT, the lamprey brain periphery contains brown-like adipocytes that maintain the same morphology as human brown adipocytes, containing multilocular lipid droplets and high mitochondrion numbers. Furthermore, we found that brown-like adipocytes in the periphery of lamprey brains responded to thermogenic reagent treatment and cold exposure and that lamprey UCP2 promoted precursor adipocyte differentiation. Molecular mapping by RNA-sequencing showed that inflammation in brown-like adipocytes treated with LPS and 25HC was enhanced compared to controls. The results of this study provide new evidence for human BAT research and demonstrate the multilocular adipose cell functions of lampreys, including: (1) providing material energy and protecting structure, (2) generating additional heat and contributing to adaptation to low-temperature environments, and (3) resisting external pathogens.

Analysis of the lamprey genotype provides insights into caspase evolution and functional divergence.

The cysteine-containing aspartate specific proteinase (caspase) family plays important roles in apoptosis and the maintenance of homeostasis in lampreys. We conducted genomic and functional comparisons of six distinct lamprey caspase groups with human counterparts to determine how these expanded molecules evolved to adapt to the changing caspase-mediated signaling pathways. Our results showed that lineage-specific duplication and rearrangement were responsible for expanding lamprey caspases 3 and 7, whereas caspases 1, 6, 8, and 9 maintained a relatively stable genome and protein structure. Lamprey caspase family molecules displayed various expression patterns and were involved in the innate immune response. Caspase 1 and 7 functioned as a pattern recognition receptor with a broad-spectrum of microbial recognition and bactericidal effect. Additionally, caspases 1 and 7 may induce cell apoptosis in a time- and dose-dependent manner; however, apoptosis was inhibited by caspase inhibitors. Thus, these molecules may reflect the original state of the vertebrates caspase family. Our phylogenetic and functional data provide insights into the evolutionary history of caspases and illustrate their functional characteristics in primitive vertebrates.

Comparison of Acoustic Structure Quantification, Transient Elastography (FibroScan) and Histology in Patients with Chronic Hepatitis B and without Moderate to Severe Hepatic Steatosis.

The purpose of this study was to compare acoustic structure quantification (ASQ) with transient elastography for staging liver fibrosis. One hundred eighty-two patients with chronic hepatitis B and without moderate to severe hepatic steatosis scheduled for liver biopsy underwent ASQ and transient elastography examinations. All ASQ parameters, including total mode, total average, red mode, red average, red standard deviation, blue mode, blue average, blue standard deviation and focal disturbance (FD) ratio and liver stiffness obtained via transient elastography were found to correlate with fibrosis stage (Spearman's r = 0.783, 0.791, 0.750, 0.771, 0.544, 0.718, 0.691, 0.439, 0.815 and 0.814, respectively; all p values < 0.001). Among the ASQ parameters, the FD ratio had the highest correlation with the stage of fibrosis. The areas under the receiver operating characteristic curves (AUCs) of FD ratio and liver stiffness were 0.911 and 0.906 for F ≥ F1, 0.918 and 0.882 for F ≥ F2, 0.911 and 0.914 for F ≥ F3 and 0.926 and 0.978 for F = F4, respectively. There was no significant difference in AUCs between FD ratio and liver stiffness in predicting different stages of fibrosis (p = 0.062-0.912). ASQ is a promising technique for assessing liver fibrosis in the absence of moderate to severe hepatic steatosis.

Noninvasive evaluation of liver fibrosis using real-time tissue elastography and transient elastography (FibroScan).

OBJECTIVES: The purpose of this study was to assess liver fibrosis with real-time tissue elastography and to compare the results with those of transient elastographic (FibroScan; Echosens, Paris, France) measurements by using liver biopsy as the reference standard. METHODS: Real-time tissue elastography and percutaneous liver biopsy were performed in 166 patients with chronic hepatitis B (estimation group). The relationship between the parameters obtained via real-time tissue elastography and the hepatic fibrosis stage was evaluated by a stepwise multiple linear regression, and the regression equation was used to calculate the liver fibrosis index. The diagnostic performance of the liver fibrosis index was validated and compared with FibroScan in 121 other patients with chronic hepatitis B (validation group). RESULTS: The liver fibrosis index was calculated as follows: liver fibrosis index = 0.043 low-strain area ratio + 4.520 skewness + 0.033 mean - 1.002 kurtosis. The liver fibrosis index and liver stiffness measured by FibroScan were both significantly associated with the fibrosis stage in the validation group (r= 0.667 and 0.664, respectively; both P< .001). The areas under the receiver operating characteristic curves for the liver fibrosis index and liver stiffness were 0.880 and 0.909 for predicting substantial fibrosis (scores ≥F2), 0.868 and 0.874 for predicting severe fibrosis (≥F3), and 0.752 and 0.815 for predicting cirrhosis (F4), respectively. CONCLUSIONS: Real-time tissue elastography is an effective method for assessing liver fibrosis, with diagnostic performance similar to that of transient elastography.

Indirect prediction of liver fibrosis by quantitative measurement of spleen stiffness using the FibroScan system.

OBJECTIVES: To evaluate quantitative measurement of spleen stiffness for indirect assessment of liver fibrosis in patients with chronic hepatitis B and to correlate spleen stiffness with liver stiffness using pathologic examination as a reference standard. METHODS: Sixty patients with clinically confirmed chronic hepatitis B (n = 54) and liver cirrhosis (n = 6) were enrolled. Quantitative stiffness measurements (kilopascals) were obtained from spleen and liver parenchyma with the FibroScan system (Echosens, Paris, France). Correlation analyses were performed between spleen and liver stiffness and between spleen stiffness and liver fibrosis stages. The diagnostic performance of spleen stiffness for indirect prediction of liver fibrosis was estimated by receiver operating characteristic curves. RESULTS: Both spleen and liver stiffness increased as liver fibrosis progressed. Spleen stiffness values had a positive correlation with liver stiffness values in all patients (Pearson r = 0.810; P < .001). The correlation between spleen stiffness and fibrosis stages was statistically significant (Spearman r = 0.833; P < .001). The areas under the receiver operating characteristic curves for spleen stiffness were 0.902 (95% confidence interval [CI], 0.825-0.978) for stage S1 (fibrous portal expansion and limited perisinusoidal or lobular fibrosis) or higher, 0.927 (95% CI, 0.852-1.0) for S2 (periportal fibrosis and few fibrous septa but intact architecture) or higher, 0.962 (95% CI, 0.918-1.0) for S3 (numerous fibrous septa with architectural distortion but no obvious cirrhosis) or higher, and 0.983 (95% CI, 0.957-1.0) for S4 (cirrhosis) (all P < .001). The differences between the areas under the curves for spleen and liver stiffness in liver fibrosis staging were not statistically significant (P = .115-.756). CONCLUSIONS: Quantitative measurement of spleen stiffness is a feasible and promising technique for estimating liver fibrosis. The overall diagnostic performance of spleen stiffness for liver fibrosis staging is comparable with that of liver stiffness.