LECT2 Functionality in Metabolic Disorders and Inflammation

Leukocyte cell-derived chemotaxin 2 (LECT2) is a hepatocyte-derived cytokine that has emerged as a crucial link between metabolic stress and inflammatory responses. Initially recognised for its chemotactic activity, LECT2 is now classified as a hepatokine that senses hepatic lipid overload and communicates with peripheral tissues. Elevated circulating levels of LECT2 are associated with obesity, insulin resistance and non-alcoholic fatty liver disease (NAFLD), where it promotes recruitment and activation of pro-inflammatory macrophages. Conversely, genetic ablation or experimental suppression of LECT2 ameliorates insulin sensitivity and attenuates tissue inflammation in preclinical models. Mechanistic studies indicate that LECT2 engages receptors such as Tie1 and c-Met to activate signalling cascades—most notably JNK and NF-κB—thereby skewing macrophage polarisation towards an M1 phenotype and amplifying cytokine release. Beyond the liver, LECT2 dysregulation has been linked to adipose inflammation, dyslipidaemia and fibrotic progression in multiple organs. These multifaceted roles underline the potential of LECT2 as both a biomarker and a therapeutic target for preventing the transition from benign steatosis to chronic inflammatory disease in metabolic disorders.

Research from Nature Portfolio

Recent studies have clarified how LECT2 drives hepatic inflammation in non-alcoholic steatohepatitis (NASH). In human liver biopsies, LECT2 expression correlates positively with body mass index and the expression of inflammatory genes such as CCR2 and TLR4. In diet-induced steatosis models, mice lacking Lect2 exhibit a marked reduction in M1-like liver macrophages, diminished phosphorylation of JNK in Kupffer cells and lower levels of TNFα and NOS2 transcripts. These observations demonstrate that LECT2 not only senses steatosis but actively polarises resident macrophages to a pro-inflammatory state, thereby promoting the progression from simple steatosis to NASH. Targeting LECT2 signalling may therefore dissociate hepatic fat accumulation from inflammation.

LECT2 Functionality in Metabolic Disorders and Inflammation publication trend

The graph below shows the total number of articles in lect2 functionality in metabolic disorders and inflammation across all publications each year (not limited to Nature Index journals).

Technical terms

LECT2: A liver-derived secreted protein acting as a hepatokine and cytokine to link metabolic perturbations to immune activation.

Hepatokine: A bioactive factor produced by hepatocytes that exerts endocrine, paracrine or autocrine effects on metabolism and inflammation.

Steatosis: Accumulation of lipid droplets within hepatocytes, commonly referred to as fatty liver.

Macrophage polarisation: The process by which macrophages adopt pro-inflammatory (M1) or anti-inflammatory (M2) functional phenotypes.

NAFLD: Non-alcoholic fatty liver disease, encompassing a range of liver conditions characterised by excessive fat deposition not attributable to alcohol.

NASH: Non-alcoholic steatohepatitis, an advanced form of NAFLD marked by hepatocellular injury and inflammation.

References

1. Association of leukocyte cell-derived chemotaxin 2 (LECT2) with NAFLD, metabolic syndrome, and atherosclerosis. PLOS ONE (2017).
2. LECT2 as a hepatokine links liver steatosis to inflammation via activating tissue macrophages in NASH. Scientific Reports (2021).
3. Rapid response of the steatosis-sensing hepatokine LECT2 during diet-induced weight cycling in mice. Biochemical and Biophysical Research Communications (2016).
4. Regulatory network and interplay of hepatokines, stellakines, myokines and adipokines in nonalcoholic fatty liver diseases and nonalcoholic steatohepatitis. Frontiers in Endocrinology (2022).