Low-protein diet during gestation and lactation increases hepatic lipid accumulation through autophagy and histone deacetylase

Huan Wang, Guanying Bianca Xu, Diego Hernandez-Saavedra, Hong Chen, Yuan Xiang Pan

Research output: Contribution to journalArticlepeer-review

Abstract

Low-protein diet during gestation and lactation increases hepatic lipid accumulation through autophagy and histone deacetylase. Am J Physiol Endocrinol Metab 319: E11-E25, 2020. First published January 7, 2020; doi:10.1152/ajpendo.00263.2019.-The present study examined the mechanism of a low-protein (LP) diet on hepatic lipid metabolism during gestation and lactation. Timed-pregnant Sprague-Dawley rats were fed a control or an LP diet during gestation and lactation. LP dams had increased hepatic triglyceride accumulation and a significantly higher aspartate/alanine transaminase ratio, accompanied by a decrease in the circulating very low-density/low-density lipoprotein ratio. Microtubuleassociated protein 1 light-chain 3β (LC3B) expression was stimulated in LP dams along with increased histone acetylation. LP diet induced colocalization of the LC3 binding motif interacting proteins apolipoprotein B (APOB) or microsomal triglyceride transfer protein (MTTP) with LC3B, suggesting autophagic degradation. Histone deacetylase 3 (HDAC3) is found necessary to prevent lipid accumulation in response to amino acid deprivation in HepG2 cells. LC3B-mediated APOB protein degradation is related to increases in lipid accumulation. HDAC3 regulated LC3B-induced lipid accumulation potentially through autophagic degradation of APOB and MTTP in response to amino acid limitation caused by a low-protein diet.

Original languageEnglish (US)
Pages (from-to)E11-E25
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume319
Issue number1
DOIs
StatePublished - Jul 2020

Keywords

  • Amino acid response
  • Autophagy
  • Histone modification
  • Protein deficiency

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

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