Orally Ingested Self-Powered Stimulators for Targeted Gut-Brain Axis Electrostimulation to Treat Obesity and Metabolic Disorders

Adv Mater. 2024 May;36(21):e2310351. doi: 10.1002/adma.202310351. Epub 2024 Apr 16.

Abstract

Obesity is a significant health concern that often leads to metabolic dysfunction and chronic diseases. This study introduces a novel approach to combat obesity using orally ingested self-powered electrostimulators. These electrostimulators consist of piezoelectric BaTiO3 (BTO) particles conjugated with capsaicin (Cap) and aim to activate the vagus nerve. Upon ingestion by diet-induced obese (DIO) mice, the BTO@Cap particles specifically target and bind to Cap-sensitive sensory nerve endings in the gastric mucosa. In response to stomach peristalsis, these particles generate electrical signals. The signals travel via the gut-brain axis, ultimately influencing the hypothalamus. By enhancing satiety signals in the brain, this neuromodulatory intervention reduces food intake, promotes energy metabolism, and demonstrates minimal toxicity. Over a 3-week period of daily treatments, DIO mice treated with BTO@Cap particles show a significant reduction in body weight compared to control mice, while maintaining their general locomotor activity. Furthermore, this BTO@Cap particle-based treatment mitigates various metabolic alterations associated with obesity. Importantly, this noninvasive and easy-to-administer intervention holds potential for addressing other intracerebral neurological diseases.

Keywords: capsaicin; metabolic dysfunction; piezoelectric material; vagus nerve stimulation; weight control.

MeSH terms

  • Administration, Oral
  • Animals
  • Barium Compounds
  • Brain-Gut Axis
  • Capsaicin / administration & dosage
  • Capsaicin / pharmacology
  • Electric Stimulation Therapy / methods
  • Male
  • Metabolic Diseases* / drug therapy
  • Metabolic Diseases* / metabolism
  • Metabolic Diseases* / therapy
  • Mice
  • Mice, Inbred C57BL
  • Obesity* / metabolism
  • Obesity* / therapy
  • Titanium / chemistry

Substances

  • Titanium
  • Capsaicin
  • barium titanate(IV)
  • Barium Compounds