By Tarun Sai Lomte Reviewed by Lily Ramsey, LLM Jul 1 2024
In a recent study published in Nature Metabolism, researchers showed that ketogenic diet (KD)-induced bile acids (BAs) are protective against obesity.
Study: Ketogenic diet-induced bile acids protect against obesity through reduced calorie absorption . Image Credit: Elena Shashkina/Shutterstock.com Background
Obesity is associated with various health conditions, such as cardiovascular disease, cancer, diabetes, and non-alcoholic fatty liver disease, warranting effective therapeutics to mitigate its health burden.
KD induces a unique metabolic profile and is often associated with being an effective treatment for intractable epilepsy and other conditions.
Evidence suggests alterations in the gut microbiota and metabolites may be involved in KD-induced protection against intestinal inflammation and epileptic seizure.
Gut microbiota/metabolites have been proposed to facilitate metabolic changes induced by KD in rodents and humans. Nevertheless, which microbes and metabolites contribute to KD-induced effects are unknown. The study and findings
In this study, researchers showed that a ketogenic diet (KD) helps protect against obesity. Mice were fed either a standard chow diet (CD) or KD for seven weeks. KD significantly lowered fasting glucose levels and body weight. Metabolomics analysis revealed notable changes in the metabolic profile of KD-fed mice, with 22 metabolites increasing and 18 decreasing.
Next, mice were fed CD, KD, or methionine-supplemented KD (KDM) for seven weeks. Methionine supplementation reversed the KD-induced reductions in glucose levels and body weight and lowered serum levels of six taurine-conjugated bile acids (BAs). KD-fed mice had reduced levels of certain unconjugated BAs, which KDM restored.
When gut microbiota were depleted, body weight and glucose differences between the KD and KDM groups disappeared. Fecal microbiota transplantation (FMT) from KD mice to CD-fed mice led to weight loss and improved glucose tolerance, while FMT from KDM mice had no effect. Related StoriesStudy reveals brain health benefits of intermittent fasting and healthy diet plansIntermittent fasting outperforms traditional drugs in managing early type 2 diabetesSpecific bacteria in the gut associated with food addiction
Further tests showed that KD altered gut microbiota composition, reducing alpha diversity, which KDM restored. KDM reversed specific bacterial strains affected by KD. Energy absorption studies indicated that KD-fed mice had higher fecal energy content, suggesting less calorie absorption.
RNA sequencing of ileal tissues showed that treatment with certain bile acids (TUDCA or TDCA) downregulated a gene linked to obesity (CAR1). These treatments also reduced lipid accumulation in cells, caused weight loss, and decreased intestinal lipid absorption in mice.
In diabetic and obese mouse models, TUDCA and TDCA treatments led to weight loss, lower fasting glucose levels, improved glucose tolerance, and reduced liver fat. Human studies found that lower plasma levels of certain conjugated BAs correlated with higher body mass index and fasting glucose levels.
In summary, this study highlights the potential of KD and specific bile acid treatments in managing obesity and metabolic health by altering gut microbiota and metabolism. Conclusions
The study revealed the impact of KD on the gut microbiota. KD increased serum TUDCA and TDCA, reducing fasting glucose levels and body weight in mice. Treatment with TUDCA or TDCA as protective against obesity in different mouse models.
Overall, the findings unravel novel host–gut microbiota interactions and support TUDCA and TDCA as potential drug candidates for managing obesity and related complications. Journal reference:
Li X, Yang J, Zhou X, et al. (2024) Ketogenic diet-induced bile acids protect against obesity through reduced calorie absorption. Nat Metab. doi: 10.1038/s42255-024-01072-1. https://www.nature.com/articles/s42255-024-01072-1