Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015695 (fatty liver)
 13,941 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent articles have reported an association between fatty liver disease and systemic insulin resistance in humans, but the causal relationship remains unclear. The liver may contribute to muscle insulin resistance by releasing secretory proteins called hepatokines. Here we demonstrate that leukocyte cell-derived chemotaxin 2 (LECT2), an energy-sensing hepatokine, is a link between obesity and skeletal muscle insulin resistance. Circulating LECT2 positively correlated with the severity of both obesity and insulin resistance in humans. LECT2 expression was negatively regulated by starvation-sensing kinase adenosine monophosphate-activated protein kinase in H4IIEC hepatocytes. Genetic deletion of LECT2 in mice increased insulin sensitivity in the skeletal muscle. Treatment with recombinant LECT2 protein impaired insulin signaling via phosphorylation of Jun NH2-terminal kinase in C2C12 myocytes. These results demonstrate the involvement of LECT2 in glucose metabolism and suggest that LECT2 may be a therapeutic target for obesity-associated insulin resistance.
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PMID:LECT2 functions as a hepatokine that links obesity to skeletal muscle insulin resistance. 2447 97

The liver is a central regulator of systemic energy homeostasis and has a pivotal role in glucose and lipid metabolism. Impaired gluconeogenesis and dyslipidemia are often observed in patients with nonalcoholic fatty liver disease (NAFLD). The liver is now recognized to be an endocrine organ that secretes hepatokines, which are proteins that regulate systemic metabolism and energy homeostasis. Hepatokines are known to contribute to the pathogenesis of metabolic syndrome, NAFLD, type 2 diabetes (T2DM), and cardiovascular diseases (CVDs). In this review, we focus on the roles of two major hepatokines, fetuin-A and fibroblast growth factor 21 (FGF21), as well as recently-redefined hepatokines, such as selenoprotein P, angiopoietin-like protein 4 (ANGPTL4), and leukocyte cell-derived chemotaxin 2 (LECT2). We also assess the biology and molecular mechanisms of hepatokines in the context of their potential as therapeutic targets for metabolic disorders and cardiovascular diseases.
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PMID:Implication of hepatokines in metabolic disorders and cardiovascular diseases. 2705 96