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Elevated levels of the gut microbe-derived metabolite trimethylamine N-oxide (TMAO) are associated with cardiometabolic disease risk. However, the mechanism(s) linking TMAO production to human disease are incompletely understood. Initiation of the metaorganismal TMAO pathway begins when dietary choline and related metabolites are converted to trimethylamine (TMA) by gut bacteria. Gut microbe-derived TMA can then be further oxidized by host flavin-containing monooxygenases to generate TMAO. Previously, we showed that drugs lowering both TMA and TMAO protect mice against obesity via rewiring of host circadian rhythms (Schugar et al., 2022). Although most mechanistic studies in the literature have focused on the metabolic end product TMAO, here we have instead tested whether the primary metabolite TMA alters host metabolic homeostasis and circadian rhythms via trace amine-associated receptor 5 (TAAR5). Remarkably, mice lacking the host TMA receptor (Taar5-/-) have altered circadian rhythms in gene expression, metabolic hormones, gut microbiome composition, and diverse behaviors. Also, mice genetically lacking bacterial TMA production or host TMA oxidation have altered circadian rhythms. These results provide new insights into diet-microbe-host interactions relevant to cardiometabolic disease and implicate gut bacterial production of TMA and the host receptor that senses TMA (TAAR5) in the physiologic regulation of circadian rhythms in mice.
Pubmed ID: 41608868
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NHLBI provides leadership for a national program in diseases of the heart, blood vessels, lung, and blood; blood resources; and sleep disorders. Since October 1997, the NHLBI has also had administrative responsibility for the NIH Woman''s Health Initiative. The Institute plans, conducts, fosters, and supports an integrated and coordinated program of basic research, clinical investigations and trials, observational studies, and demonstration and education projects. The National Heart, Lung, and Blood Institute (NHLBI) provides global leadership for a research, training, and education program to promote the prevention and treatment of heart, lung, and blood diseases and enhance the health of all individuals so that they can live longer and more fulfilling lives. The NHLBI stimulates basic discoveries about the causes of disease, enables the translation of basic discoveries into clinical practice, fosters training and mentoring of emerging scientists and physicians, and communicates research advances to the public. It creates and supports a robust, collaborative research infrastructure in partnership with private and public organizations, including academic institutions, industry, and other government agencies. The Institute collaborates with patients, families, health care professionals, scientists, professional societies, patient advocacy groups, community organizations, and the media to promote the application of research results and leverage resources to address public health needs. The NHLBI also collaborates with international organizations to help reduce the burden of heart, lung, and blood diseases worldwide.
View all literature mentionsLeadership in the national effort to reduce alcohol-related problems. It does this by by: * Conducting and supporting research in a wide range of scientific areas including genetics, neuroscience, epidemiology, health risks and benefits of alcohol consumption, prevention, and treatment; * Coordinating and collaborating with other research institutes and Federal Programs on alcohol-related issues; * Collaborating with international, national, state, and local institutions, organizations, agencies, and programs engaged in alcohol-related work; and * Translating and disseminating research findings to health care providers, researchers, policymakers, and the public. The Institute''s efforts to fulfill its mission are guided by the NIAAA vision to support and promote, through research and education, the best science on alcohol and health for the benefit of all by: * Increasing the understanding of normal and abnormal biological functions and behavior relating to alcohol use; * Improving the diagnosis, prevention, and treatment of alcohol use disorders; and * Enhancing quality health care. Research opportunities to increase our understanding of why, how, and when people drink, and why and how some people develop alcohol use disorders, are set forth in the NIAAA Strategic Plan for Research
View all literature mentionsNational institute whose mission is to reduce the burden of neurological disease - a burden borne by every age group, by every segment of society, by people all over the world. To accomplish this goal the NINDS supports and conducts basic, translational, and clinical research on the normal and diseased nervous system. The Institute also fosters the training of investigators in the basic and clinical neurosciences, and seeks better understanding, diagnosis, treatment, and prevention of neurological disorders. NINDS: * Conducts, fosters, coordinates, and guides research on the causes, prevention, diagnosis, and treatment of neurological disorders and stroke, and supports basic research in related scientific areas. * Provides grants-in-aid to public and private institutions and individuals in fields related to its areas of interest, including research project, program project, and research center grants. * Operates a program of contracts for the funding of research and research support efforts in selected areas of institute need. * Provides individual and institutional fellowships to increase scientific expertise in neurological fields. * Conducts a diversified program of intramural and collaborative research in its own laboratories, branches, and clinics. * Collects and disseminates research information related to neurological disorders.
View all literature mentionsA software which acquires and processes data sets, primarily through the Xcalibur system.
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
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