Botulinum Injection Into the Proximal Intestinal Wall of Diet-Induced Obese Mice
Leads to Weight Loss and Improves Glucose and Fat Tolerance.
Authors Sundaresan S, Antoun J, Banan B, Adcock J, Johnson C, Claire B, Dixon K, Flynn
J, Shibao CA, Abumrad N
Submitted By Submitted Externally on 11/2/2022
Status Published
Journal Diabetes
Year 2022
Date Published 7/1/2022
Volume : Pages 71 : 1424 - 1438
PubMed Reference 35476783
Abstract Botulinum neurotoxin (available commercially as BOTOX) has been used
successfully for treatment of several neuromuscular disorders, including
blepharospasm, dystonia, spasticity, and cerebral palsy in children. Our data
demonstrate that injection of Botox into the proximal intestinal wall of
diet-induced obese (DIO) mice induces weight loss and reduces food intake. This
was associated with amelioration of hyperglycemia, hyperlipidemia, and
significant improvement of glucose tolerance without alteration of energy
expenditure. We also observed accelerated gastrointestinal transit and
significant reductions in glucose and lipid absorption, which may account, at
least in part, for the observed weight loss and robust metabolic benefits,
although possible systemic effects occurring as a consequence of central and/or
peripheral signaling cannot be ignored. The observed metabolic benefits were
found to be largely independent of weight loss, as demonstrated by pair-feeding
experiments. Effects lasted ~8 weeks, for as long as the half-life of Botox as
reported in prior rodent studies. These results have valuable clinical
implications. If the observed effects are translatable in humans, this approach
could lay the foundation for therapeutic approaches geared toward robust and
sustained weight loss, mimicking some of the benefits of bariatric operations
without its cost and complications.