Rapid response of the steatosis-sensing hepatokine LECT2 during diet-induced weight cycling in mice

•Mouse LECT2 responded rapidly during weight cycling, preceding weight alterations.•Weight cycling attenuated LECT2 production, liver fat, and hyperinsulinemia in mice.•Serum LECT2 levels positively correlated liver fat, but not adipose tissue weight.•Measurement of blood LECT2 may be useful for body weight management in obesity.

Dieting often leads to body weight cycling involving repeated weight loss and regain. However, little information is available regarding rapid-response serum markers of overnutrition that predict body weight alterations during weight cycling. Here, we report the rapid response of serum leukocyte cell-derived chemotaxin 2 (LECT2), a hepatokine that induces insulin resistance in skeletal muscle, during diet-induced weight cycling in mice. A switch from a high-fat diet (HFD) to a regular diet (RD) in obese mice gradually decreased body weight but rapidly decreased serum LECT2 levels within 10 days. In contrast, a switch from a RD to a HFD rapidly elevated serum LECT2 levels. Serum LECT2 levels showed a positive correlation with liver triglyceride contents but not with adipose tissue weight. This study demonstrates the rapid response of LECT2 preceding body weight alterations during weight cycling in mice and suggests that measurement of serum LECT2 may be clinically useful in the management of obesity.