Role of Acid‐Sensing Ion Channels 1a in the Regulation of Obesity and the Gut Microbiota

TL;DR

This study shows that deleting a specific ion channel in rats leads to weight gain and changes in gut bacteria, suggesting a link between the channel, obesity, and gut microbiota.

Contribution

The study reveals a novel role for ASIC1a in regulating obesity and gut microbiota through metabolic and microbiota-based mechanisms.

Findings

Asic1a deletion in rats caused increased body weight, fat mass, glucose intolerance, and insulin resistance on both chow and high-fat diets.

Asic1a deletion altered gut microbiota, increasing Bacteroides and Akkermansia, and fecal microbiota transplants from these rats increased weight gain in germ-free mice.

The findings suggest that ASIC1a influences metabolic homeostasis and gut microbiota, which in turn affect body composition.

Abstract

Acid‐sensing ion channels are proton‐activated ion channels predominantly found in the nervous system. They are well known to affect metabolic and neurological health, yet their role in obesity and gut physiology remains unclear. This study investigates how systemic deletion of Asic1a influences obesity, metabolic, and gut‐based outcomes.

Employing male and female rats with systemic Asic1a deletion (Asic1a
−/−), metabolic, gut, and fecal microbiota (16S rRNA sequencing) measures were assessed following chow diet or high‐fat diet administration for 8 weeks. Fecal microbiota transplantation into germ‐free mice was carried out as a proof‐of‐concept approach to assess the gut microbiota's direct impact.

On a chow diet, Asic1a deletion resulted in significant gains in body weight, fat mass, glucose intolerance, and insulin resistance in both male and female rats compared to wild‐type controls. These effects were exacerbated with high‐fat diet administration. Asic1a
−/− reshaped the gut microbiota, characterized by the enrichment of Bacteroides and Akkermansia. Microbiota transplantation from Asic1a
−/− rats to recipient germ‐free mice increased body weight gain relative to those from wild‐type rats, implicating the potential role of gut microbiota.

Results provide evidence that ASIC1a plays a role in regulating metabolic homeostasis and the gut microbiota impacting body composition.

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