Abstract
Tsukushi (TSK) is a member of the small leucine-rich proteoglycan family that controls developmental processes and organogenesis. TSK was also identified as a new hepatokine, which is mainly expressed in the liver, and is secreted by hepatocytes, to regulate energy and glycolipid metabolism in response to nonalcoholic fatty liver disease. However, the role of plasma TSK, especially its role in the general population, has not been fully addressed. We investigated the associations between plasma TSK concentration and several metabolic markers, including fibroblast growth factor 21 (FGF21), a hepatokine, and adiponectin, an adipokine, in 253 subjects (men/women: 114/139) with no medication in the Tanno–Sobetsu Study, which employed a population-based cohort. There was no significant sex difference in plasma TSK concentration, and the level was positively correlated with the fatty liver index (FLI) (r = 0.131, p = 0.038), levels of insulin (r = 0.295, p < 0.001) and levels of FGF21 (r = 0.290, p < 0.001), and was negatively correlated with the total cholesterol level (r = −0.124, p = 0.049). There was no significant correlation between the TSK level and body mass index, waist circumference, adiponectin, high-density lipoprotein cholesterol or total bile acids. The multivariable regression analysis showed that high levels of insulin and FGF21 and a low level of total cholesterol were independent determinants of plasma TSK concentration, after adjustment for age, sex and FLI. In conclusion, plasma TSK concentration is independently associated with high levels of insulin and FGF21, a hepatokine, and a low level of total cholesterol, but not with adiposity and adiponectin, in a general population of subjects who have not taken any medications.
Highlights
TSK was originally identified in the lens of chicks, and this molecule was named after its expression pattern in chick embryos, which is similar to the shape of the Japanese horsetail plant, Tsukushi [2]
In the present study, we investigated the associations between plasma TSK concentration and several metabolic markers, including fibroblast growth factor 21 (FGF21), a hepatokine, and adiponectin, an adipokine, in a general population without medication, to avoid the effects of drugs on the TSK level
There were no significant correlations between TSK level and body mass index, waist circumference and levels of adiponectin, high-density lipoprotein (HDL) cholesterol and total bile acids
Summary
It has been shown that the hepatic expression and plasma concentration of TSK are induced by feeding and are regulated by melanocortin-4 receptor signaling, and that TSK deficiency in mice augments feedinginduced c-Fos expression in the paraventricular nucleus of the hypothalamus, illustrating physiological crosstalk between TSK and the central regulatory circuit in maintaining energy balance and metabolic homeostasis [8]. Another group showed that ablation of TSK did not affect the thermogenic capacity in brown adipose tissue, did not protect against the development of obesity and did not show improvements in glucose metabolism [9]. In the present study, we investigated the associations between plasma TSK concentration and several metabolic markers, including fibroblast growth factor 21 (FGF21), a hepatokine, and adiponectin, an adipokine, in a general population without medication, to avoid the effects of drugs on the TSK level
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