Hepatic Meteorin-like and Krüppel-like Factor 3 are Associated with Weight Loss and Liver Injury.

Objective: Laparoscopic adjustable gastric banding (LAGB) was found to be effective in reducing body weight and improving insulin resistance in patients with obesity and non-alcoholic fatty liver disease (NAFLD). The adipokine/myokine meteorin-like (METNRL) is an important regulator of whole-body energy expenditure. Krüppel-like factor 3 (KLF3), a regulator of METRNL expression in eosinophils, inhibits the beiging of adipose tissue in mice and therefore regulates adipose tissue development.

Methods: Thirty-three obese patients undergoing LAGB were included in the study. The hepatic and adipose tissue expression of and was determined before (t0) and 6 months after (t6) LABG. The human liver cancer cell line (HepG2) was stimulated with cytokines and fatty acids and and expressions were analyzed.

Results: LAGB-associated weight loss was correlated with decreased hepatic expression. The expression of and in hepatic-and adipose tissues correlated before and after LAGB. Individuals with augmented LAGB-induced weight loss (>20 kg) showed lower hepatic and expression before and after LAGB than patients with <20 kg weight loss. and levels were higher in patients with higher NAFLD activity scores. HepG2 stimulation with interleukin-1β, tumor necrosis factor-α, palmitic acid but not interleukin-6, oleic acid, or lipopolysaccharide, induced the expression of one or both investigated adipokines.

Conclusions: The novel description of METRNL and KLF3 as hepatokines could pave the way to target their production and/or signaling in obesity, NAFLD, and related disorders. Both proteins may act as possible biomarkers to estimate weight loss after bariatric surgery.