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

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.

Key words::

• FATTY LIVER
• MENOPAUSE
• SREBP1
• ABCA1
• LDL RECEPTOR
• PPARα
• EMBLICA OFFICINALIS
• INSIG-2

ACKNOWLEDGEMENTS

We gratefully acknowledge the technical assistance of Mr Sankar P. in carrying out Western blotting procedures. Z. B. developed the concept and Z. B., S. M. K and D. T. P. designed the experiment. S. M. K. performed the study and collected and analyzed the data. S. M. K. and D. T. P. prepared the manuscript. S. E. J. carried out histopathological examination. P. H. A. and M. G. S. gave inputs during the preparation of the manuscript. All authors read and approved the final version of the manuscript.

Conflict of interest The authors report no conflict of interest relevant to the contents of this article.

Source of funding This work was supported by the Institutional Intramural research grant in favor of the corresponding author (Z.B.). It was also supported by the Indian Council of Medical Research (ICMR), New Delhi, towards research fellowships to the first author (S.M.K.).

Supplementary material available online

Supplementary Data: Animals and interventions, Evaluation of liver function, Preparation of tissue homogenates, Western blot analyses