Background Excessive backfat deposition lowering carcass grade is a major concern in the pig industry,especially in most breeds of obese type pigs.The mechanisms involved in adipogenesis and fat accumulation in pigs r...Background Excessive backfat deposition lowering carcass grade is a major concern in the pig industry,especially in most breeds of obese type pigs.The mechanisms involved in adipogenesis and fat accumulation in pigs remain unclear.Lysine 2-hydroxyisobutyrylation(Khib),is a novel protein post-translational modification(PTM),which play an important role in transcription,energy metabolism and metastasis of cancer cells,but its role in adipogenesis and fat accumulation has not been shown.Results In this study,we first analyzed the modification levels of acetylation(Kac),Khib,crotonylation(Kcr)and succinylation(Ksu)of fibro-adipogenic progenitors(FAPs),myogenic precursors(Myo)and mesenchymal stem cells(MSCs)with varied differentiation potential,and found that only Khib modification in FAPs was significantly higher than that in MSCs.Consistently,in parallel with its regulatory enzymes lysine acetyltransferase 5(KAT5)and histone deacetylase 2(HDAC2)protein levels,the Khib levels increased quadratically(P<0.01)during adipogenic differentiation of FAPs.KAT5 knockdown in FAPs inhibited adipogenic differentiation,while HDAC2 knockdown enhanced adipogenic differentiation.We also demonstrated that Khib modification favored to adipogenic differentiation and fat accumulation by comparing Khib levels in FAPs and backfat tissues both derived from obese-type pigs(Laiwu pigs)and lean-type pigs(Duroc pigs),respectively.Accordingly,the expression patterns of KAT5 and HDAC2 matched well to the degree of backfat accumulation in obese-and lean-type pigs.Conclusions From the perspective of protein translational modification,we are the first to reveal the role of Khib in adipogenesis and fat deposition in pigs,and provided new clues for the improvement of fat accumulation and distribution as expected via genetic selection and nutritional strategy in obese-type pigs.展开更多
Cold stress is an important factor that limits apple production. In this study, we examined the tissue-cultured plantlets of apple rootstocks ‘M9T337' and ‘60-160', which are resistant and sensitive to cold ...Cold stress is an important factor that limits apple production. In this study, we examined the tissue-cultured plantlets of apple rootstocks ‘M9T337' and ‘60-160', which are resistant and sensitive to cold stress, respectively. The enriched pathways of differentially expressed genes(DEGs) and physiological changes in ‘M9T337' and ‘60-160' plantlets were clearly different after cold stress(1°C) treatment for 48 h, suggesting that they have differential responses to cold stress. The differential expression of WRKY transcription factors in the two plantlets showed that MdWRKY40is and MdWRKY48 are potential regulators of cold tolerance. When we overexpressed MdWRKY40is and MdWRKY48in apple calli, the overexpression of MdWRKY48 had no significant effect on the callus, while MdWRKY40is overexpression promoted anthocyanin accumulation, increased callus cold tolerance, and promoted the expression of anthocyanin structural gene MdDFR and cold-signaling core gene MdCBF2. Yeast one-hybrid screening and electrophoretic mobility shift assays showed that MdWRKY40is could only bind to the MdDFR promoter. Yeast twohybrid screening and bimolecular fluorescence complementation showed that MdWRKY40is interacts with the CBF2inhibitor MdMYB15L through the leucine zipper(LZ). When the LZ of MdWRMY40is was knocked out, MdWRKY40is overexpression in the callus did not affect MdCBF2 expression or callus cold tolerance, indicating that MdWRKY40is acts in the cold signaling pathway by interacting with MdMYB15L. In summary, MdWRKY40is can directly bind to the MdDFR promoter in order to promote anthocyanin accumulation, and it can also interact with MdMYB15L to interfere with its inhibitory effect on MdCBF2, indirectly promoting MdCBF2 expression, and thereby improving cold tolerance.These results provide a new perspective for the cold-resistance mechanism of apple rootstocks and a molecular basis for the screening of cold-resistant rootstocks.展开更多
目的:探讨小陷胸汤合防己茯苓汤联合二甲双胍治疗肥胖2型糖尿病痰热互结证的临床疗效。方法:将70例初诊肥胖2型糖尿病痰热互结证患者按照随机数字表分为治疗组与对照组各35例。两组患者均遵循常规糖尿病饮食方案、合理运动。对照组患者...目的:探讨小陷胸汤合防己茯苓汤联合二甲双胍治疗肥胖2型糖尿病痰热互结证的临床疗效。方法:将70例初诊肥胖2型糖尿病痰热互结证患者按照随机数字表分为治疗组与对照组各35例。两组患者均遵循常规糖尿病饮食方案、合理运动。对照组患者应用二甲双胍片治疗,治疗组患者在此基础上应用小陷胸汤合防己茯苓汤治疗。疗程为3个月。比较两组患者中医证候积分、肥胖指标、糖代谢指标、胰岛功能、微炎症指标及不良反应发生情况。结果:对照组总有效率为72.73%(24/33),治疗组总有效率为94.12%(32/34),治疗组总有效率高于对照组(P<0.05)。两组患者治疗后中医证候积分、空腹血糖(FBG)、餐后2 h血糖(2 h PBG)、糖化血红蛋白(HbA1c)、体质量、体质量指数(BMI)、腰围、腰臀比(WHR)、空腹胰岛素(FINS)、胰岛素抵抗指数(HOMA-IR)、血清超敏C反应蛋白(hs-CRP)、血清肿瘤坏死因子-α(TNF-α)水平均较治疗前降低(P<0.01),且治疗后治疗组患者中医证候积分、FBG、2 h PBG、HbA1c、体质量、BMI、腰围、FINS、HOMA-IR、血清hs-CRP、血清TNF-α水平均低于对照组(P<0.01或P<0.05);两组患者治疗后胰岛素敏感指数(In ISI)及胰岛β细胞功能指数(HOMA-β)水平均较治疗前升高(P<0.01),且治疗后治疗组患者In ISI及HOMA-β均高于对照组(P<0.01)。两组不良反应发生率比较,差异无统计学意义(P>0.05)。结论:小陷胸汤合防己茯苓汤联合二甲双胍能够有效改善肥胖2型糖尿病痰热互结证患者临床症状,降低患者血糖,减轻体质量,改善胰岛素抵抗和炎症指标。展开更多
基金financially supported by the National Key Research and Development Program of China(Grant No.2023YFD1301300)。
文摘Background Excessive backfat deposition lowering carcass grade is a major concern in the pig industry,especially in most breeds of obese type pigs.The mechanisms involved in adipogenesis and fat accumulation in pigs remain unclear.Lysine 2-hydroxyisobutyrylation(Khib),is a novel protein post-translational modification(PTM),which play an important role in transcription,energy metabolism and metastasis of cancer cells,but its role in adipogenesis and fat accumulation has not been shown.Results In this study,we first analyzed the modification levels of acetylation(Kac),Khib,crotonylation(Kcr)and succinylation(Ksu)of fibro-adipogenic progenitors(FAPs),myogenic precursors(Myo)and mesenchymal stem cells(MSCs)with varied differentiation potential,and found that only Khib modification in FAPs was significantly higher than that in MSCs.Consistently,in parallel with its regulatory enzymes lysine acetyltransferase 5(KAT5)and histone deacetylase 2(HDAC2)protein levels,the Khib levels increased quadratically(P<0.01)during adipogenic differentiation of FAPs.KAT5 knockdown in FAPs inhibited adipogenic differentiation,while HDAC2 knockdown enhanced adipogenic differentiation.We also demonstrated that Khib modification favored to adipogenic differentiation and fat accumulation by comparing Khib levels in FAPs and backfat tissues both derived from obese-type pigs(Laiwu pigs)and lean-type pigs(Duroc pigs),respectively.Accordingly,the expression patterns of KAT5 and HDAC2 matched well to the degree of backfat accumulation in obese-and lean-type pigs.Conclusions From the perspective of protein translational modification,we are the first to reveal the role of Khib in adipogenesis and fat deposition in pigs,and provided new clues for the improvement of fat accumulation and distribution as expected via genetic selection and nutritional strategy in obese-type pigs.
基金supported by the Natural Science Foundation of Shandong Province, China (ZR2021MC045)the Key Research & Development Plan (Major Scientific and Technological Innovation Project) of Shandong Province, China (2021LZGC024)the earmarked fund for China Agriculture Research System(CARS-27)。
文摘Cold stress is an important factor that limits apple production. In this study, we examined the tissue-cultured plantlets of apple rootstocks ‘M9T337' and ‘60-160', which are resistant and sensitive to cold stress, respectively. The enriched pathways of differentially expressed genes(DEGs) and physiological changes in ‘M9T337' and ‘60-160' plantlets were clearly different after cold stress(1°C) treatment for 48 h, suggesting that they have differential responses to cold stress. The differential expression of WRKY transcription factors in the two plantlets showed that MdWRKY40is and MdWRKY48 are potential regulators of cold tolerance. When we overexpressed MdWRKY40is and MdWRKY48in apple calli, the overexpression of MdWRKY48 had no significant effect on the callus, while MdWRKY40is overexpression promoted anthocyanin accumulation, increased callus cold tolerance, and promoted the expression of anthocyanin structural gene MdDFR and cold-signaling core gene MdCBF2. Yeast one-hybrid screening and electrophoretic mobility shift assays showed that MdWRKY40is could only bind to the MdDFR promoter. Yeast twohybrid screening and bimolecular fluorescence complementation showed that MdWRKY40is interacts with the CBF2inhibitor MdMYB15L through the leucine zipper(LZ). When the LZ of MdWRMY40is was knocked out, MdWRKY40is overexpression in the callus did not affect MdCBF2 expression or callus cold tolerance, indicating that MdWRKY40is acts in the cold signaling pathway by interacting with MdMYB15L. In summary, MdWRKY40is can directly bind to the MdDFR promoter in order to promote anthocyanin accumulation, and it can also interact with MdMYB15L to interfere with its inhibitory effect on MdCBF2, indirectly promoting MdCBF2 expression, and thereby improving cold tolerance.These results provide a new perspective for the cold-resistance mechanism of apple rootstocks and a molecular basis for the screening of cold-resistant rootstocks.
文摘目的:探讨小陷胸汤合防己茯苓汤联合二甲双胍治疗肥胖2型糖尿病痰热互结证的临床疗效。方法:将70例初诊肥胖2型糖尿病痰热互结证患者按照随机数字表分为治疗组与对照组各35例。两组患者均遵循常规糖尿病饮食方案、合理运动。对照组患者应用二甲双胍片治疗,治疗组患者在此基础上应用小陷胸汤合防己茯苓汤治疗。疗程为3个月。比较两组患者中医证候积分、肥胖指标、糖代谢指标、胰岛功能、微炎症指标及不良反应发生情况。结果:对照组总有效率为72.73%(24/33),治疗组总有效率为94.12%(32/34),治疗组总有效率高于对照组(P<0.05)。两组患者治疗后中医证候积分、空腹血糖(FBG)、餐后2 h血糖(2 h PBG)、糖化血红蛋白(HbA1c)、体质量、体质量指数(BMI)、腰围、腰臀比(WHR)、空腹胰岛素(FINS)、胰岛素抵抗指数(HOMA-IR)、血清超敏C反应蛋白(hs-CRP)、血清肿瘤坏死因子-α(TNF-α)水平均较治疗前降低(P<0.01),且治疗后治疗组患者中医证候积分、FBG、2 h PBG、HbA1c、体质量、BMI、腰围、FINS、HOMA-IR、血清hs-CRP、血清TNF-α水平均低于对照组(P<0.01或P<0.05);两组患者治疗后胰岛素敏感指数(In ISI)及胰岛β细胞功能指数(HOMA-β)水平均较治疗前升高(P<0.01),且治疗后治疗组患者In ISI及HOMA-β均高于对照组(P<0.01)。两组不良反应发生率比较,差异无统计学意义(P>0.05)。结论:小陷胸汤合防己茯苓汤联合二甲双胍能够有效改善肥胖2型糖尿病痰热互结证患者临床症状,降低患者血糖,减轻体质量,改善胰岛素抵抗和炎症指标。
