Short-Chain Fatty Acid Receptors and Blood Pressure Regulation: Council on Hypertension Mid-Career Award for Research Excellence 2021

Xu, Jiaojiao; Moore, Brittni N.; Pluznick, Jennifer L.

doi:10.1161/hypertensionaha.122.18558

Cited by 33 publications

(19 citation statements)

References 130 publications

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“…The activation of GPR 43 and OLFR78 can increase BP. Conversely, they can be offset by GPR41 resulting in vasodilatation [20]. We found that CKD enhanced renal expression of GPR43 and OLFR78 and these increases were suppressed by AC treatment.…”

Section: Discussionmentioning

confidence: 61%

“…SCFAs regulate BP in a manner that is differentially modulated by the activities of multiple SCFA receptors [20]. The activation of GPR 43 and OLFR78 can increase BP.…”

Section: Discussionmentioning

confidence: 99%

“…SCFAs are major gut microbiota-derived metabolites and have an important role in modulating renal physiology and BP [20]. Table 3 reveals the impact of adenine and AC on plasma concentrations of SCFA in rats at 9 weeks of age.…”

Section: Plasma Scfa Levels and Renal Scfa Receptorsmentioning

confidence: 99%

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Renoprotective Effects of Solid-State Cultivated Antrodia cinnamomea in Juvenile Rats with Chronic Kidney Disease

Tain,

Chang-Chien,

Lin

et al. 2023

Nutrients

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Antrodia cinnamomea (AC), a medicinal mushroom, has multiple beneficial actions, such as acting as a prebiotic. The incidence of chronic kidney disease (CKD) in children has steadily increased year by year, and CKD is related to gut microbiota dysbiosis. Herein, we investigated the renoprotection of solid-state cultivated AC in adenine-induced CKD juvenile rats. CKD was induced in 3-week-old male rats by feeding with adenine (0.5%) for three weeks. Treated groups received oral administration of AC extracts at either a low (10 mg/kg/day) or high dose (100 mg/kg/day) for six weeks. At nine weeks of age, the rats were sacrificed. Renal outcomes, blood pressure, and gut microbiome composition were examined. Our results revealed that AC treatment, either low- or high-dose, improved kidney function, proteinuria, and hypertension in CKD rats. Low-dose AC treatment increased plasma concentrations of short-chain fatty acids (SCFAs). Additionally, we observed that AC acts like a prebiotic by enriching beneficial bacteria in the gut, such as Akkermansia and Turicibacter. Moreover, the beneficial action of AC against CKD-related hypertension might also be linked to the inhibition of the renin-angiotensin system. This study brings new insights into the potential application of AC as a prebiotic dietary supplement in the prevention and treatment of pediatric CKD.

show abstract

Section: Discussionmentioning

confidence: 61%

“…SCFAs regulate BP in a manner that is differentially modulated by the activities of multiple SCFA receptors [20]. The activation of GPR 43 and OLFR78 can increase BP.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Renoprotective Effects of Solid-State Cultivated Antrodia cinnamomea in Juvenile Rats with Chronic Kidney Disease

Tain,

Chang-Chien,

Lin

et al. 2023

Nutrients

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“…Indeed, SCFA signaling is complex, and this complexity presents a clear challenge. For example, multiple SCFAs activate multiple receptors, including, but not limited to, GPR41, GPR43, GPR109a, olfr78, and olfr558, some of which are found in multiple tissues, and some of which can heterodimerize (Xu et al., 2022). For example, SCFAs produced by the gut microbiota modulate blood pressure via olfr78 and GPR41 (Pluznick et al., 2013).…”

Section: Discussionmentioning

confidence: 99%

Olfr78, a novel short‐chain fatty acid receptor, regulates glucose homeostasis and gut GLP‐1 secretion in mice

Wang,

Li,

Guo

et al. 2023

Food Frontiers

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Olfr78, which is a novel receptor for short‐chain fatty acid (SCFA) acetate and propionate, plays essential roles in some cellular processes. The present study aimed to investigate the role of olfr78 in regulating energy metabolism and delineate the underlying mechanisms using olfr78−/− mice. Deletion of olfr78 did not influence the adiposity of mice fed either normal chow or a high‐fat diet (HFD). However, olfr78−/− mice exhibited glucometabolic dysfunction, as evidenced by increased fasting blood glucose levels, decreased serum insulin levels, and impaired oral glucose tolerance under HFD feeding. When compared to wild‐type (WT) mice, olfr78 deficiency enhanced HFD‐induced gluconeogenesis and increased the mRNA expression of key gluconeogenic genes in the liver and kidney. Quantitative real‐time PCR results revealed that olfr78 expression was higher in the colon compared with other tissues in WT mice. Analysis of the gut microbiota in the feces of olfr78−/− mice using 16S rRNA gene sequencing revealed altered relative abundances of some representative SCFAs producers along with decreased levels of SCFAs, including propionic, isobutyric, 2‐methylbutyric, valeric, isovaleric, and 4‐methylvaleric acids. Importantly, mice lacking olfr78 had low circulating levels of glucagon‐like peptide 1 (GLP‐1). In the STC‐1 enteroendocrine cell line, propionate and acetate induced the secretion of the gut hormone GLP‐1, and this effect was partially abolished by olfr78 siRNA‐mediated knockdown. Together, these results suggest a previously undescribed, specific regulatory role for gut olfr78 in glucose homeostasis and highlight olfr78 as a potential target for diabetes treatment.

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“…CHD, congenital heart disease; PAMP, pathogen-associated molecular pattern; TLR, Toll-like receptor. increased peripheral vascular resistance, vascular remodeling, and renal sodium absorption [51]. SCFAs have a protective effect on atherosclerotic cardiovascular disease (ACVD).…”

Section: Microbiome Metabolites and Cardiovascular Diseasesmentioning

confidence: 99%

From heart to gut: Exploring the gut microbiome in congenital heart disease

Liu,

Huang,

et al. 2023

iMeta

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Congenital heart disease (CHD) is a prevalent birth defect and a significant contributor to childhood mortality. The major characteristics of CHD include cardiovascular malformations and hemodynamical disorders. However, the impact of CHD extends beyond the circulatory system. Evidence has identified dysbiosis of the gut microbiome in patients with CHD. Chronic hypoxia and inflammation associated with CHD affect the gut microbiome, leading to alterations in its number, abundance, and composition. The gut microbiome, aside from providing essential nutrients, engages in direct interactions with the host immune system and indirect interactions via metabolites. The abnormal gut microbiome or its products can translocate into the bloodstream through an impaired gut barrier, leading to an inflammatory state. Metabolites of the gut microbiome, such as short‐chain fatty acids and trimethylamine N‐oxide, also play important roles in the development, treatment, and prognosis of CHD. This review discusses the role of the gut microbiome in immunity, gut barrier, neurodevelopment, and perioperative period in CHD. By fostering a better understanding of the cross‐talk between CHD and the gut microbiome, this review aims to contribute to improve clinical management and outcomes for CHD patients.

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Short-Chain Fatty Acid Receptors and Blood Pressure Regulation: Council on Hypertension Mid-Career Award for Research Excellence 2021

Cited by 33 publications

References 130 publications

Renoprotective Effects of Solid-State Cultivated Antrodia cinnamomea in Juvenile Rats with Chronic Kidney Disease

Renoprotective Effects of Solid-State Cultivated Antrodia cinnamomea in Juvenile Rats with Chronic Kidney Disease

Olfr78, a novel short‐chain fatty acid receptor, regulates glucose homeostasis and gut GLP‐1 secretion in mice

From heart to gut: Exploring the gut microbiome in congenital heart disease

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