Garcinol promotes hepatic gluconeogenesis by inhibiting P300/CBP-associated factor in late-pregnant sows

Br J Nutr. 2021 Jul 14;126(1):1-8. doi: 10.1017/S000711452000375X. Epub 2020 Sep 24.

Abstract

Disorder of hepatic glucose metabolism is the characteristic of late-pregnant sows. The purpose of our study was to look into the mechanism of garcinol on the improvement of hepatic gluconeogenic enzyme in late-pregnant sows. Thirty second- and third-parity sows (Duroc × Yorkshire × Landrace, n 10/diet) were fed a basal diet (control) or that diet supplemented with 100 mg/kg (Low Gar) or 500 mg/kg (High Gar) garcinol from day 90 of gestation to the end of farrowing. The livers were processed to measure enzymatic activity. Hepatocytes from pregnant sows were transfected with P300/CBP-associating factor (PCAF) small interfering RNA (siRNA) or treated with garcinol. Dietary garcinol had no effect on average daily feed intake, body weight (BW), backfat and BW gain of late-pregnant sows. Garcinol promoted plasma glucose levels in pregnant sows and newborn piglets. Garcinol up-regulated hepatic gluconeogenic enzyme expression and decreased PCAF activity. Garcinol had no effect on the expression of PPAR-γ co-activator 1α (PGC-1α) and Forkhead box O1 (FOXO1) but significantly increased their activity and decreased their acetylation in late-pregnant sows. Transfection of PCAF siRNA to hepatocytes of pregnant sows increased PGC-1α and FOXO1 activities. Furthermore, in hepatocytes of pregnant sows, garcinol treatment also up-regulated the activities of PGC-1α and FOXO1 and inhibited the acetylation of PGC-1α and FOXO1. Garcinol improves hepatic gluconeogenic enzyme expression in late-pregnant sows, and this may be due to the mechanism of down-regulating the acetylation of PGC-1α and FOXO1 induced by PCAF in isolated hepatocytes.

Keywords: Garcinol; Glucose; Late-pregnant sows; Liver; P300/CBP-associating factor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Diet
  • Female
  • Forkhead Box Protein O1 / metabolism
  • Gluconeogenesis*
  • Liver* / drug effects
  • Liver* / metabolism
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / metabolism*
  • Pregnancy
  • RNA, Small Interfering / metabolism
  • Swine
  • Terpenes / pharmacology*
  • p300-CBP Transcription Factors / antagonists & inhibitors*

Substances

  • Forkhead Box Protein O1
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • RNA, Small Interfering
  • Terpenes
  • p300-CBP Transcription Factors
  • garcinol