Furthermore, adipocyte‐specific knock‐out of metrnl exacerbates insulin resistance induced by a high‐fat diet (HFD), whereas adipocyte‐specific transgenic overexpression of metrnl prevents insulin resistance induced by HFD or leptin deletion, suggesting that adipocyte metrnl ameliorates overall insulin resistance by acting on local adipose tissue in an autocrine/paracrine fashion [23]. This evidence concerns the gene LEP and Insulin resistance.