Microbial metabolite delta-valerobetaine is a diet-dependent obesogen.
Ken H LiuJoshua A OwensBejan SaeediCatherine E CohenMoriah P BellissimoCrystal R NaudinTrevor DarbySamuel DruzakKristal Maner-SmithMichael OrrXin HuJolyn FernandesMary Catherine CamachoSarah Hunter-ChangLibusha KellyChunyu MaThota GaneshSamantha M YeligarKaran UppalYoung-Mi GoJessica A AlvarezMiriam B VosThomas R ZieglerMichael H WoodworthColleen S KraftRheinallt M JonesEric A OrtlundAndrew S NeishDean P JonesPublished in: Nature metabolism (2021)
Obesity and obesity-related metabolic disorders are linked to the intestinal microbiome. However, the causality of changes in the microbiome-host interaction affecting energy metabolism remains controversial. Here, we show the microbiome-derived metabolite δ-valerobetaine (VB) is a diet-dependent obesogen that is increased with phenotypic obesity and is correlated with visceral adipose tissue mass in humans. VB is absent in germ-free mice and their mitochondria but present in ex-germ-free conventionalized mice and their mitochondria. Mechanistic studies in vivo and in vitro show VB is produced by diverse bacterial species and inhibits mitochondrial fatty acid oxidation through decreasing cellular carnitine and mitochondrial long-chain acyl-coenzyme As. VB administration to germ-free and conventional mice increases visceral fat mass and exacerbates hepatic steatosis with a western diet but not control diet. Thus, VB provides a molecular target to understand and potentially manage microbiome-host symbiosis or dysbiosis in diet-dependent obesity.
Keyphrases
- high fat diet induced
- weight loss
- insulin resistance
- adipose tissue
- physical activity
- metabolic syndrome
- fatty acid
- type diabetes
- high fat diet
- weight gain
- skeletal muscle
- oxidative stress
- cell death
- microbial community
- hydrogen peroxide
- reactive oxygen species
- body mass index
- nitric oxide
- single molecule
- adverse drug
- electronic health record