Summary: A new study shows that acetate delivered directly to the large intestine, combined with specific gut bacteria, can significantly reduce body fat and liver mass in both normal and obese mice. Researchers used an acetylated cellulose supplement called AceCel to release acetate in the colon and promote the growth and activity of Bacteroides species.
When AceCel reaches the distal large intestine in the presence of Bacteroides bacteria, the microbial community ferments more carbohydrates in the gut, reducing the amount of simple sugars available for absorption. This shift lowers carbohydrate use and increases fat oxidation in the host, producing metabolic effects similar to fasting or a ketogenic diet and resulting in reduced fat accumulation.
Key Facts:
- AceCel + Bacteroides: Weight and liver-fat reduction occur only when acetate reaches the colon and Bacteroides species are present.
- Metabolic Shift: AceCel promotes fatty acid oxidation over carbohydrate oxidation, favoring fat burning like fasting or low-carb states.
- Gut-Driven Mechanism: Bacteroides increase carbohydrate fermentation in the gut, depleting host-accessible sugars and reducing glycogen storage in the liver.
Source: RIKEN
Researchers at the RIKEN Center for Integrative Medical Sciences (IMS), led by Hiroshi Ohno, have identified a gut microbiome–dependent strategy to reduce obesity.
The team demonstrated that supplementing the gut with acetate, via an acetylated cellulose formulation called AceCel, reduces fat mass and liver size in both wild-type and obese mice—provided the gut contains Bacteroides species. AceCel is designed to protect acetate through the upper intestine and release it in the distal large intestine, where fiber fermentation normally occurs.
In experiments comparing AceCel-fed mice to controls, mice receiving AceCel lost body fat without losing muscle mass. The effect was specific to acetate among short-chain fatty acids tested, indicating acetate itself drives the benefit.
Metabolic measurements showed that AceCel-fed mice derived more resting energy from liver fat and less from carbohydrates than control mice. This metabolic profile resembles that induced by fasting or a ketogenic diet and helps explain the observed weight loss and reduced liver glycogen storage.
Microbiome analysis revealed AceCel increases the abundance of Bacteroides species. To test causality, the researchers used mice with controlled microbiotas: germ-free mice and mice colonized with single Bacteroides species. AceCel produced no effect in germ-free mice, while colonization with any of three Bacteroides species restored the weight- and liver-fat–reducing benefits. This demonstrates the necessity of both acetate delivery and specific gut commensals for the therapeutic effect.
Mechanistically, acetate enhances carbohydrate fermentation by Bacteroides, consuming host-accessible simple sugars in the gut. With fewer absorbable sugars, the host shifts toward burning fat for energy and stores less glycogen in the liver, thereby reducing obesity-related measures.
“Developing a treatment or prevention strategy for obesity is an urgent issue that must be solved quickly,” says Hiroshi Ohno. “We found that acetylated cellulose can prevent obesity by modulating the function of the gut microbiome. Our next step is to confirm the safety and efficacy of acetylated cellulose in humans, where it could become an important ingredient in functional foods that help prevent obesity.”
About this obesity research news
Author: Adam Phillips
Source: RIKEN
Contact: Adam Phillips – RIKEN
Image: The image is credited to Neuroscience News
Original Research: Open access. “Acetylated cellulose suppresses body mass gain through gut commensals consuming host-accessible carbohydrates” by Hiroshi Ohno et al., Cell Metabolism. DOI: 10.1016/j.cmet.2025.04.013
Abstract
Acetylated cellulose suppresses body mass gain through gut commensals consuming host-accessible carbohydrates
Effective approaches to prevent and treat obesity are urgently needed. While many strategies target host metabolism directly, another promising approach is to limit nutrient availability to the host by reshaping gut microbial function. The authors report that acetylated cellulose (AceCel) markedly alters gut bacterial composition and function and reduces body mass gain in both wild-type and obese mice.
AceCel limits carbohydrate oxidation and promotes fatty acid oxidation in the liver in a microbiota-dependent manner. Acetate released from AceCel enhances carbohydrate fermentation by the gut commensal Bacteroides thetaiotaomicron, depleting host-accessible simple sugars in the gut of AceCel-fed mice. These results position AceCel as a promising prebiotic that coordinates carbohydrate metabolism between bacteria and host, offering potential as a therapeutic strategy against obesity.