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

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.

• Authors: Weilei Yao, Jun Xia, Tongxin Wang, Juan Li, Lu Huang, Feiruo Huang
• Journal: The British journal of nutrition (Br J Nutr) Vol. 126 Issue 1 Pg. 1-8 (07 14 2021) ISSN: 1475-2662 [Electronic] England
• PMID: 32967737 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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