Microbiota-mediated induction of beige adipocytes in response to dietary cues

Interactions between diet and the gut microbiota are fundamental to metabolic health, shaping energy balance and disease susceptibility<sup>1-5</sup>. However, the underlying mechanisms by which dietary and microbial factors converge to regulate host physiology remain unclear. Here we show that protein availability profoundly modulates the functional landscape of the gut microbiota and promotes remodelling of white adipose tissue (WAT). Specifically, low-protein diets (LPDs) robustly induce signature genes of browning in WAT to a similar extent to that seen in response to classical stimuli, such as cold exposure or β-adrenergic receptor activation<sup>6-8</sup>. LPD-mediated browning was markedly diminished in germ-free mice, and this defect was rescued by colonization with defined bacterial consortia made up of strains that were isolated and down-selected from the faeces of either LPD-fed mice or healthy human volunteers with <sup>18</sup>F-fluorodeoxyglucose positron emission tomography (FDG-PET)-confirmed brown- or beige-fat activity<sup>9-12</sup>. Microbiota-induced browning was mediated both by bile acids driving the activation of the farnesoid X receptor (FXR) in adipose progenitor cells, and by nrfA-encoding commensal-derived ammonia driving the expression of fibroblast growth factor 21 (FGF21) in hepatocytes. The bile acid-FXR and ammonia-FGF21 axes both have non-redundant, essential roles in promoting WAT browning. These findings highlight a mechanistic link between diet, gut microbial metabolism and adipose tissue remodelling, uncovering microbiota-dependent pathways by which the host responds to dietary cues.

Authors

Institutions

Publication Details

Journal
Nature
Published
2026-03-04
DOI
https://doi.org/10.1038/s41586-026-10205-3
Citations
1
Primary Topic
Gut microbiota and health
Type
article
Field-Weighted Citation Impact
22.24
Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

Microbiota-mediated induction of beige adipocytes in response to dietary cues

Yasuhiko Minokoshi, Satoshi Sasajima, Nobuyuki Okahashi, Damian R. Plichta et al.
1 citations
Nature
Gut microbiota and health
22.24
article

Microbiota-mediated induction of beige adipocytes in response to dietary cues

Yasuhiko Minokoshi, Satoshi Sasajima, Nobuyuki Okahashi, Damian R. Plichta, Samuel Zimmerman, Masahiro Ueda, Scott W. Behie, Orr Ashenberg, Kozue Takeshita, Koji Atarashi, Ashwin N. Skelly, Kouichi Miura, Takeshi Tanoue, Kenya Honda, Daniel R. Mende, Ramnik J. Xavier, Nicholas Pucci, Mami Matsushita, Manabu Nagayama, Yoshiaki Nakayama, Aki Minoda, Shingo Kajimura, Wataru Suda, Makoto Arita, Masayuki Saito, Hironori Yamamoto, Nicola Hetherington, Morichika Konishi, Shunji Watanabe, Tanvi Jain, Toshiro Sato, Ayumi J. A. Roochana, Ryo Igarashi
article en
1 citations

Abstract

Interactions between diet and the gut microbiota are fundamental to metabolic health, shaping energy balance and disease susceptibility<sup>1-5</sup>. However, the underlying mechanisms by which dietary and microbial factors converge to regulate host physiology remain unclear. Here we show that protein availability profoundly modulates the functional landscape of the gut microbiota and promotes remodelling of white adipose tissue (WAT). Specifically, low-protein diets (LPDs) robustly induce signature genes of browning in WAT to a similar extent to that seen in response to classical stimuli, such as cold exposure or β-adrenergic receptor activation<sup>6-8</sup>. LPD-mediated browning was markedly diminished in germ-free mice, and this defect was rescued by colonization with defined bacterial consortia made up of strains that were isolated and down-selected from the faeces of either LPD-fed mice or healthy human volunteers with <sup>18</sup>F-fluorodeoxyglucose positron emission tomography (FDG-PET)-confirmed brown- or beige-fat activity<sup>9-12</sup>. Microbiota-induced browning was mediated both by bile acids driving the activation of the farnesoid X receptor (FXR) in adipose progenitor cells, and by nrfA-encoding commensal-derived ammonia driving the expression of fibroblast growth factor 21 (FGF21) in hepatocytes. The bile acid-FXR and ammonia-FGF21 axes both have non-redundant, essential roles in promoting WAT browning. These findings highlight a mechanistic link between diet, gut microbial metabolism and adipose tissue remodelling, uncovering microbiota-dependent pathways by which the host responds to dietary cues.

Nature
Broad Institute (US), City Of Hope National Medical Center (US), Beth Israel Deaconess Medical Center (US), Howard Hughes Medical Institute (US), Harvard University (US), Radboud University Nijmegen (NL), Jichi Medical University (JP), Kobe Pharmaceutical University (JP), Keio University (JP), Hokkaido University (JP), Radboud University Medical Center (NL), Massachusetts General Hospital (US), Radboud Institute for Molecular Life Sciences (NL), National Institute for Physiological Sciences (JP), RIKEN Center for Integrative Medical Sciences (JP), Amsterdam University Medical Centers (NL), Center for Systems Biology (US), Tenshi College (JP), University of Amsterdam (NL)
Zero hunger
Openalex Percentile: Top 1%
Gut microbiota and health
22.24
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.