Hormonal
Oral administration of the intestine-selective FXR inhibitor Gly-MCA prevents and reverses high-fat diet-induced and genetic obesity, insulin resistance, and hepatic steatosis in mice by reducing intestinal ceramide biosynthesis, which restores beige fat thermogenic function.
This research identifies a specific bile acid derivative (Gly-MCA) that, when taken orally, blocks a specific receptor (FXR) in the gut. This blockage reduces harmful fats (ceramides) in the intestine, which allows body fat to burn energy more effectively, leading to weight loss and better blood sugar control in obese mice. While promising, this is currently a preclinical finding in mice and not yet an available human treatment.
Gly-MCA is a selective high-affinity FXR inhibitor that can be administered orally and prevents, or reverses, high-fat diet-induced and genetic obesity, insulin resistance and hepatic steatosis in mice. Mechanistically, the metabolic improvements with Gly-MCA depend on reduced biosynthesis of intestinal-derived ceramides, which directly compromise beige fat thermogenic function.
Why this rating
High-quality mechanistic data in mouse models, but lacks human clinical trial data for efficacy and safety.
Source
Intestine-selective farnesoid X receptor inhibition improves obesity-related metabolic dysfunction
Changtao Jiang et al. · Nature Communications · 2015
DOI 10.1038/ncomms10166
Related findings · Hormonal
- Initial treatment for type 2 diabetes should be a combination of metformin and either an SGLT-2 inhibitor or a GLP-1 receptor agonist to achieve cardiorenal protection, rather than monotherapy or older agents like sulfonylureas.Strong
- For patients with specific monogenic obesity syndromes (leptin deficiency, POMC/PCSK1/LEPR mutations), targeted pharmacotherapy (recombinant leptin or setmelanotide) is highly effective and should be prioritized, unlike in polygenic obesity.Strong
- Continued weekly administration of 2.4 mg subcutaneous semaglutide prevents weight regain and promotes further weight loss in adults with overweight or obesity, whereas switching to placebo results in significant weight regain.Strong
This is one finding among thousands. Every one is graded and traced to its source, so you can see what the evidence actually supports. Browse the research →