Obesity-Associated Neuropathy: Recent Preclinical Studies and Proposed Mechanisms

Raiza Bonomo, Sarah Kramer, Virginie M. Aubert

Research output: Contribution to journalReview articlepeer-review

1 Scopus citations


Significance: The prevalence of metabolic syndrome (MetS) and associated obesity has increased in recent years, affecting millions worldwide. One of the most common complications of obesity is damage to the peripheral nerve system, referred to as neuropathy. The lack of disease-modifying therapy for this complication is largely due to a poor understanding of the complex neurobiology underlying neuropathy. Recent preclinical studies suggest that in addition to glucotoxic events, other mechanisms, including lipid signaling, microbiome, or inflammation, may be viable targets to prevent nerve damage and neuropathic pain in obesity. Recent Advances: Clinical and preclinical studies using diet-induced obesity rodent models have identified novel interventions that improve neuropathy. Notably, mechanistic studies suggest that lipid, calcium signaling, and inflammation are converging pathways. Critical Issues: In this review, we focus on interventions and their mechanisms that are shown to ameliorate neuropathy in MetS obese models, including: (i) inhibition of a sensory neuron population, (ii), modification of dietary components, (iii) activation of nuclear and mitochondrial lipid pathways, (iv) exercise, and (v) modulation of gut microbiome composition and their metabolites. Future Directions: These past years, novel research increased our knowledge about neuropathy in obesity and discovered the involvement of nonglucose signaling. More studies are necessary to uncover the interplay between complex metabolic pathways in the peripheral nerve system of obese individuals. Further mechanistic studies in preclinical models and humans are crucial to create single- or multitarget interventions for this complex disease implying complex metabolic phenotyping. Antioxid. Redox Signal. 37, 597-612.

Original languageEnglish (US)
Pages (from-to)597-612
Number of pages16
JournalAntioxidants and Redox Signaling
Issue number7-9
StatePublished - Sep 1 2022
Externally publishedYes


  • molecular mechanism
  • neuropathy
  • obesity
  • peripheral nerve system
  • treatments

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology


Dive into the research topics of 'Obesity-Associated Neuropathy: Recent Preclinical Studies and Proposed Mechanisms'. Together they form a unique fingerprint.

Cite this