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

Exp Clin Endocrinol Diabetes. 2022 Jun;130(6):406-414. doi: 10.1055/a-1537-8950. Epub 2021 Aug 18.

Abstract

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 METNRL and KLF3 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 METNRL and KLF3 expressions were analyzed.

Results: LAGB-associated weight loss was correlated with decreased hepatic METNRL expression. The expression of METNRL and KLF3 in hepatic-and adipose tissues correlated before and after LAGB. Individuals with augmented LAGB-induced weight loss (>20 kg) showed lower hepatic METNRL and KLF3 expression before and after LAGB than patients with <20 kg weight loss. METNRL and KLF3 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.

MeSH terms

  • Adipokines
  • Gastroplasty*
  • Humans
  • Kruppel-Like Transcription Factors / metabolism*
  • Laparoscopy*
  • Non-alcoholic Fatty Liver Disease* / metabolism
  • Obesity / metabolism
  • Obesity, Morbid* / surgery
  • Weight Loss / physiology

Substances

  • Adipokines
  • KLF3 protein, human
  • Kruppel-Like Transcription Factors