Y process and may exert anti-inflammatory or pro-inflammatory functions depending on the target tissue. In this study, which included subjects without diabetes, circulating progranulin levels had a significant positive correlation with serum hsCRP and IL-6 levels, reflecting chronic subclinical inflammation. Very recently, progranulin was identified as a novel adipokine that mediates high fat diet-induced insulin resistance. In that study, insulin resistance induced by progranulin was significantly improved by a neutralizing antibody against IL-6, implicating IL-6 as a mediator of progranulininduced insulin resistance in adipocytes [7]. Interestingly, multiple regression analysis in this study showed that serum IL-6 level was an MedChemExpress CASIN independent determining factor for circulating progranulin levels, even after adjusting for other confounding risk factors. Our study demonstrates that serum progranulin is an independent maker for subclinical atherosclerosis, represented as CIMT. Atherosclerosis is a chronic inflammatory process resulting from the interaction of modified lipoprotein, macrophages, and the normal cellular elements of the arterial wall [22]. Growing evidence suggests that various adipokines are directly involved inthe process of atherosclerosis [23]. An immunohistochemical analysis of human carotid endoatherectomy specimens indicated that intimal vascular smooth muscle cells and some macrophages in human atherosclerotic plaque express progranulin [24]. Progranulin in the plaque would be cleaved into granulins, which increase IL-8 levels and drive the migration of inflammatory cells to the vessel wall [24]. A recent clinical study reported that serum progranulin levels were significantly higher in subjects with nonalcoholic fatty liver disease (NAFLD), which is now regarded as an independent cardiovascular risk factor, and were associated with adverse lipid profiles [25]. In the present study, an independent association between CIMT and serum progranulin levels, together with 22948146 age, sex, BMI, and HDL-cholesterol levels, was found in subjects without Argipressin web metabolic syndrome. On the other hand, in subjects with metabolic syndrome, age, diastolic blood pressure, and LDL-C levels were determining risk factors for CIMT. Although the exact explanation for this result is not clear, progranulin may have a major influence on the early stages of atherosclerosis, which may be associated with inflammation rather than the classical cardiovascular risk factors. CTRP3 is a newly-discovered adipokine whose structure contains a 246 amino acid sequence protein, and is regarded as an adiponectin paralog [26]. Recombinant CTRP3 reduced glucose output in cultured rat hepatoma cells by suppressing gluconeogenic genes [10], significantly inhibited LPS-induced IL-6 and TNF-a secretion in THP-1 cells, and reduced NF-kB p65 activity [12]. These results suggest the biological relevance of CTRP3’s antidiabetic and anti-inflammatory properties. In the present study, we included subjects without diabetes, and circulating CTRP3 showed significant negative correlations with metabolic risk factors, including waist circumference, serum triglyceride, and glucose levels. We also observed a significant positive correlation between serum CTRP3 levels and circulating adiponectin concentrations. However, in our previous study, serum CTRP3 levels were elevated in subjects with type 2 diabetes and showed significant positive correlation with cardiometabolic risk factors such as w.Y process and may exert anti-inflammatory or pro-inflammatory functions depending on the target tissue. In this study, which included subjects without diabetes, circulating progranulin levels had a significant positive correlation with serum hsCRP and IL-6 levels, reflecting chronic subclinical inflammation. Very recently, progranulin was identified as a novel adipokine that mediates high fat diet-induced insulin resistance. In that study, insulin resistance induced by progranulin was significantly improved by a neutralizing antibody against IL-6, implicating IL-6 as a mediator of progranulininduced insulin resistance in adipocytes [7]. Interestingly, multiple regression analysis in this study showed that serum IL-6 level was an independent determining factor for circulating progranulin levels, even after adjusting for other confounding risk factors. Our study demonstrates that serum progranulin is an independent maker for subclinical atherosclerosis, represented as CIMT. Atherosclerosis is a chronic inflammatory process resulting from the interaction of modified lipoprotein, macrophages, and the normal cellular elements of the arterial wall [22]. Growing evidence suggests that various adipokines are directly involved inthe process of atherosclerosis [23]. An immunohistochemical analysis of human carotid endoatherectomy specimens indicated that intimal vascular smooth muscle cells and some macrophages in human atherosclerotic plaque express progranulin [24]. Progranulin in the plaque would be cleaved into granulins, which increase IL-8 levels and drive the migration of inflammatory cells to the vessel wall [24]. A recent clinical study reported that serum progranulin levels were significantly higher in subjects with nonalcoholic fatty liver disease (NAFLD), which is now regarded as an independent cardiovascular risk factor, and were associated with adverse lipid profiles [25]. In the present study, an independent association between CIMT and serum progranulin levels, together with 22948146 age, sex, BMI, and HDL-cholesterol levels, was found in subjects without metabolic syndrome. On the other hand, in subjects with metabolic syndrome, age, diastolic blood pressure, and LDL-C levels were determining risk factors for CIMT. Although the exact explanation for this result is not clear, progranulin may have a major influence on the early stages of atherosclerosis, which may be associated with inflammation rather than the classical cardiovascular risk factors. CTRP3 is a newly-discovered adipokine whose structure contains a 246 amino acid sequence protein, and is regarded as an adiponectin paralog [26]. Recombinant CTRP3 reduced glucose output in cultured rat hepatoma cells by suppressing gluconeogenic genes [10], significantly inhibited LPS-induced IL-6 and TNF-a secretion in THP-1 cells, and reduced NF-kB p65 activity [12]. These results suggest the biological relevance of CTRP3’s antidiabetic and anti-inflammatory properties. In the present study, we included subjects without diabetes, and circulating CTRP3 showed significant negative correlations with metabolic risk factors, including waist circumference, serum triglyceride, and glucose levels. We also observed a significant positive correlation between serum CTRP3 levels and circulating adiponectin concentrations. However, in our previous study, serum CTRP3 levels were elevated in subjects with type 2 diabetes and showed significant positive correlation with cardiometabolic risk factors such as w.
