ArticleJCI insight2019
The hepatokine Tsukushi is released in response to NAFLD and impacts cholesterol homeostasis.
Article in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed.
- Co-Administration of Trans-Resveratrol and L-Carnitine with a High-Fat and High-Carbohydrate Diet Modulates Liver Transcriptome in Obesity-Resistant DBA/2J Mice.International journal of molecular sciences · 2026Article
- Article
- A comparison of plasma Tsukushi in adolescents with and without metabolic dysfunction-associated steatotic liver disease.Physiological reports · 2026Article
- Article
- Serum Tsukushi level is negatively associated with cholesterol efflux capacity in metabolic dysfunction-associated steatotic liver disease: a cross-sectional study.Scientific reports · 2025Article
- RNA-seq analysis reveals transcriptome changes in livers fromBiochemistry and biophysics reports · 2025Article
- Elevated Serum Tsukushi Levels and Their Association with Glycolipid Metabolism in Gestational Diabetes Mellitus Patients.Diabetes, metabolic syndrome and obesity : targets and therapy · 2025Article
- Brain-acting hepatokines: its impact on energy balance and metabolism.Frontiers in neuroscience · 2025Review
- Liver adrenoceptor alpha-1b plays a key role in energy and glucose homeostasis in female mice.American journal of physiology. Endocrinology and metabolism · 2024Article
- A new perspective on the regulation of glucose and cholesterol transport by mitochondria-lysosome contact sites.Frontiers in physiology · 2024Review
- Association of Serum Tsukushi Levels with Urinary Albumin-Creatinine Ratio in Type 2 Diabetes Patients.Diabetes, metabolic syndrome and obesity : targets and therapy · 2024Article
- Unraveling the mechanisms underlying drug-induced cholestatic liver injury: identifying key genes using machine learning techniques on human in vitro data sets.Archives of toxicology · 2023Article
- Friend or foe for obesity: How hepatokines remodel adipose tissues and translational perspective.Genes & diseases · 2023Review
- Article
- The role of hepatokines in NAFLD.Cell metabolism · 2023Review
- A review on Tsukushi: mammalian development, disorders, and therapy.Journal of cell communication and signaling · 2022Review
- Effect of Obesity and High-Density Lipoprotein Concentration on the Pathological Characteristics of Alzheimer's Disease in High-Fat Diet-Fed Mice.International journal of molecular sciences · 2022Article
- ERα-Dependent Regulation of Adropin Predicts Sex Differences in Liver Homeostasis during High-Fat Diet.Nutrients · 2022Article
- Review article: vascular effects of PPARs in the context of NASH.Alimentary pharmacology & therapeutics · 2022Review
- Hepatic PTEN Signaling Regulates Systemic Metabolic Homeostasis through Hepatokines-Mediated Liver-to-Peripheral Organs Crosstalk.International journal of molecular sciences · 2022Article
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Authors and funding
24 authors.
Funding
Abstract
Nonalcoholic fatty liver disease (NAFLD) prevails in obesity and is linked to several health complications including dyslipidemia and atherosclerosis. How exactly NAFLD induces atherogenic dyslipidemia to promote cardiovascular diseases is still elusive. Here, we identify Tsukushi (TSK) as a hepatokine induced in response to NAFLD. We show that both endoplasmic reticulum stress and inflammation promote the expression and release of TSK in mice. In humans, hepatic TSK expression is also associated with steatosis, and its circulating levels are markedly increased in patients suffering from acetaminophen-induced acute liver failure (ALF), a condition linked to severe hepatic inflammation. In these patients, elevated blood TSK levels were associated with decreased transplant-free survival at hospital discharge, suggesting that TSK could have a prognostic significance. Gain- and loss-of-function studies in mice revealed that TSK impacts systemic cholesterol homeostasis. TSK reduces circulating HDL cholesterol, lowers cholesterol efflux capacity, and decreases cholesterol-to-bile acid conversion in the liver. Our data identify the hepatokine TSK as a blood biomarker of liver stress that could link NAFLD to the development of atherogenic dyslipidemia and atherosclerosis.
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