Abstract
PurposeWhether Tsukushi (TSK) can protect against high-fat diet (HFD)-induced obesity and improve glucose metabolism remains controversial. Serum levels of TSK in the population have not been reported until now. We assessed the association among TSK level, TSKU genotype, and metabolic traits in humans.MethodsAssociations between serum TSK levels and metabolic traits were assessed in 144 Han Chinese individuals. Loci in the TSKU gene region were further genotyped in 11,022 individuals. The association between the loci and serum TSK level was evaluated using the additive genetic model. The association between the loci and their metabolic traits in humans were also verified.ResultsLower TSK levels were observed in obese subjects than in control subjects (median and interquartile range 17.78:12.07–23.28 vs. 23.81:12.54–34.56, P < 0.05). However, in obese subjects, TSK was positively associated with BMI (β ± SE: 0.63 ± 0.31, P = 0.049), visceral fat area (β ± SE: 12.15 ± 5.94, P = 0.011), and deterioration of glucose metabolism. We found that rs11236956 was associated with TSK level in obese subjects (β 95% CI 0.17, 0.07–0.26; P = 0.0007). There was also a significant association between rs11236956 and metabolic traits in our population.ConclusionsOur findings showed that serum TSK levels were associated with metabolic disorders in obese subjects. We also identified rs11236956 to be associated with serum TSK levels in obese subjects and with metabolic disorders in the total population.
Highlights
The liver is the principal organ in the regulation of systemic metabolism and energy homeostasis
We explored single nucleotide polymorphisms (SNPs), which were associated with serum TSK levels in a Han Chinese population, and analyzed the association between the SNPs and metabolic traits
Subjects with a low serum TSK level were used as a reference. f, g In the obesity subgroup, the association between serum TSK level with HOMA-β and homeostatic model assessment for insulin resistance (HOMA-IR) (P = 0.03)
Summary
The liver is the principal organ in the regulation of systemic metabolism and energy homeostasis. It directly participates in the processes of uptake, synthesis, oxidation and secretion of lipid and glucose [1]. It is recognized that the liver can secrete hepatokines to regulate other extrahepatic metabolic tissues, via autocrine, paracrine, and endocrine. Yangyang Li and Li Jin have contributed to this article. Tsukushi (TSK) is a small, secreted protein of the leucine-rich proteoglycan family, encoded by the TSKU gene. It is an organizer inducer that is involved in the development of multiple tissues [7].
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