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Smooth muscle AKG/oxgr1 signaling regulates epididymal fluid acid–base balance and sperm maturation

Life Metabolism 2022年第1期1卷 67-80页

作者： Chang Xu Yexian Yuan Cha Zhang Yuchuan Zhou Jinping Yang Huadong Yi Ishwari Gyawali Jingyi Lu Sile Guo Yunru Ji Chengquan Tan Songbo Wang Yongliang Zhang Qingyan Jiang Gang Shu Guangdong Laboratory for Lingnan Modern Agriculture National Engineering Research Center for Breeding Swine Industry and Guangdong Province Key Laboratory of Animal Nutritional RegulationCollege of Animal ScienceSouth China Agricultural UniversityGuangzhouGuangdongChina International Peace Maternity and Child Health Hospital Shanghai Key Laboratory of Embryo Original DiseasesSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina State Key Laboratory of Biocontrol Guangdong Provincial Key Laboratory for Aquatic Economic AnimalsSchool of Life SciencesSun Yat-Sen UniversityGuangzhouChina

Infertility is a global concern attributed to genetic defects,lifestyle,nutrition,and any other factors that affect the local metabolism and niche microenvironment of the reproductive system.2-Oxoglutarate receptor 1(oxgr1)is abundantly expressed in the testis;however,its cellular distribution and biological function of oxgr1 in the male reproductive system remain *** the current study,we demonstrated that oxgr1 is primarily expressed in epididymal smooth muscle cells(SMCs).Aging and heat stress significantly reduced oxgr1 expression in the *** oxgr1 global knockout and epididymal-specific oxgr1 knockdown models,we revealed that oxgr1 is essential for epididymal sperm maturation and fluid acid–base *** ofα-ketoglutaric acid(AKG),the endogenous ligand of oxgr1,effectively reversed epididymal sperm maturation disorders caused by aging and heat ***,in vitro studies showed that AKG markedly stimulated the release of instantaneous intracellular calcium from epididymal SMCs and substantially reduced the pH_(i) value in the epididymal SMCs via ***,we discovered that AKG/oxgr1 considerably increased the expression of Na^(+)/HCO_(3)^(−)cotransporter(NBCe1)mRNA in the epididymal SMCs,mediated by intracellular calcium *** local AKG/oxgr1 system changed the epididymal fluid pH value and HCO_(3)^(−)concentration,thereby regulating sperm maturation via intracellular calcium signaling and NBCe1 mRNA *** study for the first time reveals the crucial role of oxgr1 in male fertility and sheds light on the applicability of metabolic intermediates in the nutritional intervention of reproduction.

关键词： AKG oxgr1 epididymis acid-base balance sperm maturation

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AKG/oxgr1 promotes skeletal muscle blood flow and metabolism by relaxing vascular smooth muscle

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Life Metabolism 2022年第3期1卷 285-297页

作者： Jinping Yang Guli Xu Yiming Xu Pei Luo Yexian Yuan Lin Yao Jingjing Zhou Yunlong Zhu Ishwari Gyawali Chang Xu Jinlong Feng Zewei Ma Yuxian Zeng Songbo Wang Ping Gao Canjun Zhu Qingyan Jiang Gang Shu Guangdong Laboratory for Lingnan Modern Agriculture and Guangdong Province Key Laboratory of Animal Nutritional Regulation South China Animal Nutrition and Feed Science Observation and Experimental StationCollege of Animal ScienceSouth China Agricultural University483 Wushan RoadTianhe DistrictGuangzhouGuangdong 510642China School of Basic Medical Sciences The Sixth Affiliated Hospital of Guangzhou Medical UniversityQingyuan People’s HospitalGuangzhou Medical UniversityGuangzhouGuangdong 511518China South China Research Center for Acupuncture and Moxibustion Medical College of Acu-Moxi and RehabilitationGuangzhou University of Chinese MedicineGuangzhouGuangdong 510006China School of Pharmaceutical Sciences Guangzhou University of Chinese MedicineGuangzhouGuangdong 510006China

In response to contraction during exercise,skeletal muscle growth and metabolism are dynamically regulated by nerve action,blood flow,and metabolic feedback.α-Ketoglutarate(AKG),a bioactive intermediate in the tricarboxylic acid cycle released during exercise,has been shown to promote skeletal muscle ***,the underlying mechanism of AKG in regulating skeletal muscle development and metabolism is still less known.2-Oxoglutarate receptor 1(oxgr1),the endogenous AKG receptor,is found to be distributed in the vascular smooth muscle(VSM)of skeletal ***1 knockout results in skeletal muscle atrophy,accompanied by decreased expression of myosin heavy chain I(MyHC I),capillary density,and endurance exercise ***,the study found that dietary AKG supplementation increased mice endurance exercise distance,MyHC I/MyHC IIb ratio,arteriole,and capillary densities in skeletal ***,acute AKG administration gradually increased the blood flow in the lower ***,by using oxgr1 global knockout and oxgr1 VSM-specific(MYH11-Cre×oxgr1-FloxP)knockdown models,we found that oxgr1 in VSM is essential for AKG-induced improvement of skeletal muscle *** to the in vitro study,AKG expanded the cell area in VSM with a decreased intracellular pH by *** results demonstrated a novel role of AKG/oxgr1 in VSM of skeletal muscle to regulate blood flow and then enhance slow muscle fiber conversion and *** findings provide a theoretical basis for the AKG/oxgr1 signaling pathway to maintain human muscle function and improve meat production and livestock and poultry meat quality.

关键词： oxgr1 AKG smooth muscle cell skeletal muscle blood flow metabolism

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