Phyllanthus emblica Fruit Improves Obesity by Reducing Appetite and Enhancing Mucosal Homeostasis via the Gut Microbiota-Brain-Liver Axis in HFD-Induced Leptin-Resistant Rats

J Agric Food Chem. 2024 May 8;72(18):10406-10419. doi: 10.1021/acs.jafc.4c01226. Epub 2024 Apr 24.

Abstract

The impact of leptin resistance on intestinal mucosal barrier integrity, appetite regulation, and hepatic lipid metabolism through the microbiota-gut-brain-liver axis has yet to be determined. Water extract of Phyllanthus emblica L. fruit (WEPE) and its bioactive compound gallic acid (GA) effectively alleviated methylglyoxal (MG)-triggered leptin resistance in vitro. Therefore, this study investigated how WEPE and GA intervention relieve leptin resistance-associated dysfunction in the intestinal mucosa, appetite, and lipid accumulation through the microbiota-gut-brain-liver axis in high-fat diet (HFD)-fed rats. The results showed that WEPE and GA significantly reduced tissues (jejunum, brain, and liver) MG-evoked leptin resistance, malondialdehyde (MDA), proinflammatory cytokines, SOCS3, orexigenic neuropeptides, and lipid accumulation through increasing leptin receptor, tight junction proteins, antimicrobial peptides, anorexigenic neuropeptides, excretion of fecal triglyceride (TG), and short-chain fatty acids (SCFAs) via a positive correlation with the Allobaculum and Bifidobacterium microbiota. These novel findings suggest that WEPE holds the potential as a functional food ingredient for alleviating obesity and its complications.

Keywords: Phyllanthus emblica fruit; antimicrobial peptides; appetite-related neuropeptides; intestinal mucosal barrier; leptin resistance; microbiota–gut–brain–liver axis; obesity; tight junction protein.

MeSH terms

  • Animals
  • Appetite* / drug effects
  • Bacteria / drug effects
  • Bacteria / metabolism
  • Brain / drug effects
  • Brain-Gut Axis* / drug effects
  • Diet, High-Fat
  • Fruit* / chemistry
  • Gastrointestinal Microbiome / drug effects
  • Homeostasis* / drug effects
  • Humans
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / metabolism
  • Leptin / metabolism
  • Liver / drug effects
  • Liver / metabolism
  • Male
  • Obesity* / drug therapy
  • Obesity* / metabolism
  • Obesity* / microbiology
  • Phyllanthus emblica* / chemistry
  • Plant Extracts* / chemistry
  • Plant Extracts* / pharmacology
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Leptin
  • Plant Extracts