Secreted hormones play pivotal roles in tissue cross talk to maintain physiologic blood glucose and lipid levels. We previously showed that C1q/TNF-related protein 12 (CTRP12) is a novel secreted protein involved in regulating glucose metabolism whose circulating levels are reduced in obese and insulin-resistant mouse models. Its role in lipid metabolism, however, is unknown. Using a novel heterozygous mouse model, we show that the loss of a single copy of the Ctrp12 gene (also known as Fam132a and adipolin) affects whole body lipid metabolism. In Ctrp12 (+/-) male mice fed a control low-fat diet, hepatic fat oxidation was upregulated while hepatic VLDL-triglyceride secretion was reduced relative to wild-type (WT) littermates. When challenged with a high-fat diet, Ctrp12 (+/-) male mice had impaired lipid clearance in response to acute lipid gavage, reduced hepatic triglyceride secretion, and greater steatosis with higher liver triglyceride and cholesterol levels. Unlike male mice, Ctrp12 (+/-) female mice fed a control low-fat diet were indistinguishable from WT littermates. When obesity was induced by high-fat feeding, Ctrp12 (+/-) female mice developed mild insulin resistance with impaired insulin tolerance. In contrast to male mice, hepatic triglyceride secretion was increased in Ctrp12 (+/-) female mice fed a high-fat diet. Thus, in different dietary and metabolic contexts, loss of a single Ctrp12 allele affects glucose and lipid metabolism in a sex-dependent manner, highlighting the importance of genetic and environmental determinants of metabolic phenotypes.
Background: Noninvasive assessment of liver fibrosis has important clinical significance. Different techniques including two-dimensional shear-wave elastography (2D SWE) and real-time tissue elastography (RTE) are reported to be useful for the noninvasive diagnosis of hepatic fibrosis. All these techniques are affected by many factors. How to choose a reasonable method needs further studies. Purpose: This study was conducted to comparatively assess the diagnostic performance of 2D SWE and RTE in patients with Chronic Hepatitis B (CHB) and influence of inflammation on the stiffness values obtained by both techniques, so as to objectively assess the reasonable choice between these 2 elastography techniques for noninvasive assessment of hepatic fibrosis in clinical practice. Materials and Methods: Four-hundred and thirty-seven patients with CHB meeting the inclusion criteria were enrolled in the study. All patients underwent liver stiffness measurements by using 2D SWE and RTE on the same day. Histologic fibrosis was staged and inflammation activity was graded based on the METAVIR scoring system on liver biopsy specimens. Results: The liver stiffness values by using 2D SWE and RTE both increased in parallel with the degree of liver fibrosis and the grade of inflammation. However, the diagnostic efficacy of significant fibrosis and cirrhosis using 2D SWE was significantly higher than that of RTE. The 2D SWE measurement values were statistically different in different alanine aminotransferase (ALT) levels and METAVIR activity grades; however, no statistically significant differences were observed by using RTE. The diagnostic efficacy of 2D SWE significantly varied with elevated ALT levels compared with RTE. Conclusion: 2D SWE was more accurate than RTE in the assessment of significant fibrosis and cirrhosis in patients with CHB. Compared with RTE, the measurement values and diagnostic performance obtained by 2D SWE were prone to be more easily affected by the inflammation fluctuations.
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