Amla prevents fructose-induced hepatic steatosis in ovariectomized rats: role of liver FXR and LXRα

Climacteric. 2015 Apr;18(2):299-310. doi: 10.3109/13697137.2014.933408. Epub 2014 Sep 6.

Abstract

Objectives: Increased fructose consumption causes dyslipidemia and fatty liver in postmenopausal women, both independent risk factors for cardiovascular disease. This study explored the potential mechanisms by which amla (Emblica officinalis) reduced hypercholesterolemia and hypertriglyceridemia and prevented fatty liver in a fructose-fed, ovariectomized rat model of menopause.

Methods: Sham-operated and ovariectomized rats were put on a chow or high fructose diet. They were further divided into groups with or without amla. After 18 weeks of treatment, livers were harvested and subjected to Western blot and histological analyses.

Results: In all groups, amla increased the protein expression of liver farnesoid X receptor (FXR) and liver X receptor (LXR), key proteins involved in lipid metabolism. Fructose-fed rats developed fatty liver and amla prevented this. Here amla produced an exceptional rise in LXR and insulin-induced gene-2 (Insig-2) which prevented the maturation of sterol regulatory element-binding protein-1 and steroyl CoA desaturase-1, responsible for triglyceride synthesis. Amla also increased the protein expression of ATP binding cassette transporter A1 (ABCA1), involved in high density lipoprotein (HDL) synthesis as well as low density lipoprotein receptor (LDLR) responsible for uptake of LDL cholesterol. Besides this, amla increased the protein expression of peroxisome proliferator activated receptor α (PPARα) involved in β oxidation of fatty acids.

Conclusions: Amla increased the protein expression of liver FXR, LXRα, PPARα and their downstream proteins Insig-2, ABCA1 and LDLR. This property of amla to modulate some of the key proteins involved in lipid metabolism promises its usefulness as a preventive agent for dyslipidemia and hepatic steatosis.

Keywords: ABCA1; EMBLICA OFFICINALIS; FATTY LIVER; INSIG-2; LDL RECEPTOR; MENOPAUSE; PPARα; SREBP1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Fatty Acid Synthases / metabolism
  • Fatty Liver / chemically induced
  • Fatty Liver / prevention & control*
  • Female
  • Fructose / administration & dosage*
  • Intracellular Signaling Peptides and Proteins / analysis
  • Liver / chemistry
  • Liver / pathology
  • Liver X Receptors
  • Menopause
  • Organ Size / drug effects
  • Orphan Nuclear Receptors / analysis
  • Orphan Nuclear Receptors / physiology*
  • Ovariectomy
  • Phyllanthus emblica / chemistry*
  • Plant Extracts / administration & dosage*
  • Rats
  • Rats, Wistar
  • Receptors, Cytoplasmic and Nuclear / analysis
  • Receptors, Cytoplasmic and Nuclear / physiology*
  • Sterol Regulatory Element Binding Protein 1 / analysis

Substances

  • Intracellular Signaling Peptides and Proteins
  • Liver X Receptors
  • Nr1h3 protein, rat
  • Orphan Nuclear Receptors
  • Plant Extracts
  • Receptors, Cytoplasmic and Nuclear
  • Sterol Regulatory Element Binding Protein 1
  • farnesoid X-activated receptor
  • Fructose
  • Fatty Acid Synthases