Similar Insulin Regulation of Splanchnic FFA and VLDL-TG in Men with Nonalcoholic Hepatic Steatosis and Steatohepatitis.

Jeyanthini Risikesan, Sara Heebøll, Indumathi Kumarathas, Esben Søndergaard, Rakel F Johansen, Steffen Ringgaard, Niels K Aagaard, Thomas D Sandahl, Gerda E Villadsen,Lars C Gormsen,Jan Frystyk,Michael D Jensen,Henning Grønbæk,Søren Nielsen

Journal of lipid research(2024)

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Abstract
This study aimed to determine whether obese men with nonalcoholic fatty liver disease (NAFLD) display differences between those with simple steatosis vs. 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) vs. 38 (18-58) μmol/min; simple steatosis: 62 (46-78) vs. 45 (25-65) μmol/min, mean (95% CI), basal vs. clamp periods, respectively, p = 0.02 time-effect). Splanchnic palmitate release was also comparable between groups and non-significantly diminished during hyperinsulinemia. The percent palmitate delivered to the liver originating from visceral adipose tissue (VAT) 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). IN CONCLUSIONS: 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 VAT lipolysis delivered to the liver. These results suggest that FFA and VLDL-TG splanchnic balances are unaffected by NAFLD severity.
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