Obesity Affects the Microbiota-Gut-Brain Axis and the Regulation Thereof by Endocannabinoids and Related Mediators.

TitleObesity Affects the Microbiota-Gut-Brain Axis and the Regulation Thereof by Endocannabinoids and Related Mediators.
Publication TypeJournal Article
Year of Publication2020
AuthorsForte, N, Fernández-Rilo, AClara, Palomba, L, Di Marzo, V, Cristino, L
JournalInt J Mol Sci
Volume21
Issue5
Date Published2020 Feb 25
ISSN1422-0067
Abstract

The hypothalamus regulates energy homeostasis by integrating environmental and internal signals to produce behavioral responses to start or stop eating. Many satiation signals are mediated by microbiota-derived metabolites coming from the gastrointestinal tract and acting also in the brain through a complex bidirectional communication system, the microbiota-gut-brain axis. In recent years, the intestinal microbiota has emerged as a critical regulator of hypothalamic appetite-related neuronal networks. Obesogenic high-fat diets (HFDs) enhance endocannabinoid levels, both in the brain and peripheral tissues. HFDs change the gut microbiota composition by altering the Firmicutes:Bacteroidetes ratio and causing endotoxemia mainly by rising the levels of lipopolysaccharide (LPS), the most potent immunogenic component of Gram-negative bacteria. Endotoxemia induces the collapse of the gut and brain barriers, interleukin 1β (IL1β)- and tumor necrosis factor α (TNFα)-mediated neuroinflammatory responses and gliosis, which alter the appetite-regulatory circuits of the brain mediobasal hypothalamic area delimited by the median eminence. This review summarizes the emerging state-of-the-art evidence on the function of the "expanded endocannabinoid (eCB) system" or endocannabinoidome at the crossroads between intestinal microbiota, gut-brain communication and host metabolism; and highlights the critical role of this intersection in the onset of obesity.

DOI10.3390/ijms21051554
Alternate JournalInt J Mol Sci
PubMed ID32106469
PubMed Central IDPMC7084914
Grant List0003290/23-09-201 to LC / / Joint International Research Unit (JIURU) for Chemical and Biomolecular Research on the Microbiome and its impact on Metabolic Health an Nutrition (MicrMeNu) /