β-Klotho and FRS2 induction favours the operation of the FGF21-FGFR1-β-Klotho complex as evidenced by the enhancement in ERK1/2 phosphorylation, whereas that of Sestrin2 recruits LKB1 to achieved AMPK activation, thus supporting a higher energy expenditure condition that may be desirable in some metabolic disorders.
These data suggest that inhibition of Lkb1 or its downstream signalling in adipocytes could be a novel strategy to increase energy expenditure in the context of obesity, diabetes and other metabolic diseases.
This study attains a mechanistic understanding of the regulation of LKB1-AMPK axis and implicates Nur77 as a new and amenable target for the design and development of therapeutics to treat metabolic diseases.
In this study, we isolated a cell line (SAMe-deficient [SAMe-D]) from MAT1A knockout (MAT1A-KO) mouse HCC to examine the role of LKB1 in the development of liver tumors derived from metabolic disorders.