Similar insulin regulation of splanchnic FFA and VLDL-TG in men with nonalcoholic hepatic steatosis and steatohepatitis

J Lipid Res. 2024 Jul;65(7):100580. doi: 10.1016/j.jlr.2024.100580. Epub 2024 Jun 18.

Abstract

This study aimed to determine whether obese men with nonalcoholic fatty liver disease (NAFLD) display differences between those with simple steatosis versus steatohepatitis (NASH) in splanchnic and hepatic FFA and VLDL-triglycerides (VLDL-TG) balances. The study involved 17 obese men with biopsy-proven NAFLD (9 with NASH and 8 with simple steatosis). We used hepatic vein catheterization in combination with [3H]palmitate and [14C]VLDL-TG tracers to measure splanchnic palmitate and VLDL-TG uptake and release rates during basal and hyperinsulinemic conditions. Indocyanine green was used to measure splanchnic plasma flow. Splanchnic palmitate uptake was similar in the two groups and significantly reduced during hyperinsulinemia (NASH: 62 (48-77) versus 38 (18-58) μmol/min; simple steatosis: 62 (46-78) versus 45 (25-65) μmol/min, mean (95% CI), basal versus clamp periods, respectively, P = 0.02 time-effect). Splanchnic palmitate release was also comparable between groups and nonsignificantly diminished during hyperinsulinemia. The percent palmitate delivered to the liver originating from visceral adipose tissue lipolysis was similar and unchanged by hyperinsulinemia. Splanchnic uptake and release of VLDL-TG were similar between groups. Hyperinsulinemia suppressed VLDL-TG release (P <0.05 time-effect) in both groups. Insulin-mediated glucose disposal was similar in the two groups (P = 0.54). Obese men with NASH and simple steatosis have similar splanchnic uptake and release of FFA and VLDL-TG and a similar proportion of FFA from visceral adipose tissue lipolysis delivered to the liver. These results demonstrate that the splanchnic balances of FFA and VLDL-TG do not differ between obese men with NASH and those with simple steatosis.

Trial registration: ClinicalTrials.gov NCT04292977.

Keywords: VLDL; free fatty acids; insulin; lipolysis and fatty acid metabolism; lipoproteins/kinetics; liver; nonalcoholic fatty liver disease; triglycerides; visceral adipose tissue.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Fatty Acids, Nonesterified / blood
  • Fatty Acids, Nonesterified / metabolism
  • Fatty Liver / metabolism
  • Fatty Liver / pathology
  • Humans
  • Insulin* / metabolism
  • Lipoproteins, VLDL* / metabolism
  • Liver / metabolism
  • Male
  • Middle Aged
  • Non-alcoholic Fatty Liver Disease* / metabolism
  • Non-alcoholic Fatty Liver Disease* / pathology
  • Obesity / complications
  • Obesity / metabolism
  • Triglycerides* / blood
  • Triglycerides* / metabolism

Substances

  • Lipoproteins, VLDL
  • Triglycerides
  • very low density lipoprotein triglyceride
  • Insulin
  • Fatty Acids, Nonesterified

Associated data

  • ClinicalTrials.gov/NCT04292977