Akkermansia muciniphila secretes a glucagon-like peptide-1-inducing protein that improves glucose homeostasis and ameliorates metabolic disease in mice

Yoon, Hye-Kyung; Cho, Chung Hwan; Yun, Myeong Sik; Jang, Sung Jae; You, Hyun Ju; Kim, Jun Hyeong; Han, Dohyun; Hyun, Kwang; Moon, Seol Ju; Lee, Kiuk; Kim, Yeon Ji; Lee, Sung Joon; Nam, Tae Wook; Ko, Gwang Pyo

doi:10.1038/s41564-021-00880-5

Cited by 316 publications

(256 citation statements)

References 70 publications

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“…Treatment targeting the gut microbiota is an emerging therapeutic for metabolic diseases. It is reported that the gut microbiota A. muciniphila increased thermogenesis of brown adipocytes and GLP-1 secretion in HFD mice, thus improving glucose homeostasis (88). High-fiber diet elevated GLP-1 levels in patients with type 2 diabetes via promoting the growth of SCFA-producing gut microbiota, and finally improved glucose regulation (89).…”

Section: Discussionmentioning

confidence: 99%

Central Regulation of PCOS: Abnormal Neuronal-Reproductive-Metabolic Circuits in PCOS Pathophysiology

2021

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Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disease. PCOS patients are characterized by hyperandrogenemia, anovulation, and metabolic dysfunction. Hypothalamus–pituitary–ovary axis imbalance is considered as an important pathophysiology underlying PCOS, indicating that central modulation, especially the abnormal activation of hypothalamic GnRH neurons plays a vital role in PCOS development. Increased GnRH pulse frequency can promote LH secretion, leading to ovarian dysfunction and abnormal sex steroids synthesis. By contrast, peripheral sex steroids can modulate the action of GnRH neurons through a feedback effect, which is impaired in PCOS, thus forming a vicious cycle. Additionally, hypothalamic GnRH neurons not only serve as the final output pathway of central control of reproductive axis, but also as the central connection point where reproductive function and metabolic state inter-regulate with each other. Metabolic factors, such as insulin resistance and obesity in PCOS patients can regulate GnRH neurons activity, and ultimately regulate reproductive function. Besides, gut hormones act on both brain and peripheral organs to modify metabolic state. Gut microbiota disturbance is also related to many metabolic diseases and has been reported to play an essential part in PCOS development. This review concludes with the mechanism of central modulation and the interaction between neuroendocrine factors and reproductive or metabolic disorders in PCOS development. Furthermore, the role of the gut microenvironment as an important part involved in the abnormal neuronal–reproductive–metabolic circuits that contribute to PCOS is discussed, thus offering possible central and peripheral therapeutic targets for PCOS patients.

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Section: Discussionmentioning

confidence: 99%

Central Regulation of PCOS: Abnormal Neuronal-Reproductive-Metabolic Circuits in PCOS Pathophysiology

2021

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“…Lactis strain, and these novel bacteria demonstrated an insulinotropic effect in in vitro and in vivo experiments [ 128 ]. Similarly, a protein secreted from one A. muciniphila strain has been shown to induce GLP-1 secretion that resulted in improved metabolic condition in HFD mice [ 132 ]. Along the same line, Amuc_1100, a protein from the outer membrane of A .…”

Section: Discussionmentioning

confidence: 99%

Role of Postbiotics in Diabetes Mellitus: Current Knowledge and Future Perspectives

Cabello-Olmo

Araña

Urtasun

et al. 2021

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In the last decade, the gastrointestinal microbiota has been recognised as being essential for health. Indeed, several publications have documented the suitability of probiotics, prebiotics, and symbiotics in the management of different diseases such as diabetes mellitus (DM). Advances in laboratory techniques have allowed the identification and characterisation of new biologically active molecules, referred to as “postbiotics”. Postbiotics are defined as functional bioactive compounds obtained from food-grade microorganisms that confer health benefits when administered in adequate amounts. They include cell structures, secreted molecules or metabolic by-products, and inanimate microorganisms. This heterogeneous group of molecules presents a broad range of mechanisms and may exhibit some advantages over traditional “biotics” such as probiotics and prebiotics. Owing to the growing incidence of DM worldwide and the implications of the microbiota in the disease progression, postbiotics appear to be good candidates as novel therapeutic targets. In the present review, we summarise the current knowledge about postbiotic compounds and their potential application in diabetes management. Additionally, we envision future perspectives on this topic. In summary, the results indicate that postbiotics hold promise as a potential novel therapeutic strategy for DM.

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“…Besides, other means of regulation such as adapted expression levels, genomic background, buffering mutations or allele-specific expression might offset the effects of deleterious mutations (94,95). Moreover, the gut microbiota is thought to modulate energy metabolism and to secrete GLP-1 inducing factors that improve glucose homeostasis (96). Given the low number of carriers for the majority of the proglucagon missense variants, it is likely that much larger cohorts will be needed to delineate deleterious from benign mutations.…”

Section: Discussionmentioning

confidence: 99%

Mutational Landscape of the Proglucagon-Derived Peptides

et al. 2021

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Strong efforts have been placed on understanding the physiological roles and therapeutic potential of the proglucagon peptide hormones including glucagon, GLP-1 and GLP-2. However, little is known about the extent and magnitude of variability in the amino acid composition of the proglucagon precursor and its mature peptides. Here, we identified 184 unique missense variants in the human proglucagon gene GCG obtained from exome and whole-genome sequencing of more than 450,000 individuals across diverse sub-populations. This provides an unprecedented source of population-wide genetic variation data on missense mutations and insights into the evolutionary constraint spectrum of proglucagon-derived peptides. We show that the stereotypical peptides glucagon, GLP-1 and GLP-2 display fewer evolutionary alterations and are more likely to be functionally affected by genetic variation compared to the rest of the gene products. Elucidating the spectrum of genetic variations and estimating the impact of how a peptide variant may influence human physiology and pathophysiology through changes in ligand binding and/or receptor signalling, are vital and serve as the first important step in understanding variability in glucose homeostasis, amino acid metabolism, intestinal epithelial growth, bone strength, appetite regulation, and other key physiological parameters controlled by these hormones.

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Akkermansia muciniphila secretes a glucagon-like peptide-1-inducing protein that improves glucose homeostasis and ameliorates metabolic disease in mice

Cited by 316 publications

References 70 publications

Central Regulation of PCOS: Abnormal Neuronal-Reproductive-Metabolic Circuits in PCOS Pathophysiology

Central Regulation of PCOS: Abnormal Neuronal-Reproductive-Metabolic Circuits in PCOS Pathophysiology

Role of Postbiotics in Diabetes Mellitus: Current Knowledge and Future Perspectives

Mutational Landscape of the Proglucagon-Derived Peptides

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