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In this study, the effects of particle distribution and anodizing time on the microstructure and corrosion resistance of the TiB2 particle-reinforced Al-Zn-Mg-Cu composite were investigated. Relationships between TiB2 particle distribution, anodizing time, coating growth rule, and corrosion resistance were characterized and discussed using an optical microscope, a scanning electron microscope, an electrochemical test, and a salt spray test. Dispersion of TiB2 particles by powder metallurgy improved the corrosion resistance of the anodized coating on composites. Compared with the matrix, the corrosion potential (Ecorr) of the anodized coating shifted to the positive direction, and the corrosion current density (icorr) decreased. Meanwhile, the icorr of the coating decreased initially and then increased with the extension of the anodization time. The corrosion resistance of the coating was optimal at an anodization time of 20 min. The corrosion resistance of the composite was determined by both the porosity and thickness of the coating. Additionally, all samples treated by potassium dichromate sealing had no corrosion points after a 336-h salt spray test, demonstrating an excellent corrosion resistance suitable for harsh environmental applications in industry. [ABSTRACT FROM AUTHOR]

Interface characteristics are of great importance in mechanical performance for multi-phases heat-resistant Al alloys. Herein, Al3Sc precipitates were created at both Al/Al9FeNi interface and Al matrix inside Al–Fe-Ni eutectic alloy by microalloyed Sc. Critically, Al3Sc interface precipitates were found to alleviate local lattice distortion at the Al/Al9FeNi interface to improve interface stability. Therefore, this alloy showed superior creep properties over available reports. The underlying mechanisms were quantitatively elucidated by elevated load transfer effect from interface precipitates and enhanced threshold stress from matrix precipitates. Generally, this work provided a solid understanding to optimize the creep property of eutectic Al alloys by manipulating interface structures. This work reports that Al3Sc precipitates at Al/Al9FeNi interface can enhance load transfer effect of eutectic phase from microscopic/macroscopic factors, illustrating fundamental mechanisms for creep improvement of eutectic Al alloy. [ABSTRACT FROM AUTHOR]

Background and Purpose: Hydrogen sulfide (H2 S) plays important roles as a gasotransmitter in pathologies. Increased expression of the E3 ubiquitin ligase, muscle RING finger-1 (MuRF1), may be involved in diabetic cardiomyopathy. Here we have investigated whether and how exogenous H2 S alleviates cardiac muscle degradation through modifications of MuRF1 S-sulfhydration in db/db mice.Experimental Approach: Neonatal rat cardiomyocytes were treated with high glucose (40 mM), oleate (100 μM), palmitate (400 μM), and NaHS (100 μM) for 72 hr. MuRF1 was silenced with siRNA technology and mutation at Cys44 . Endoplasmic reticulum stress markers, MuRF1 expression, and ubiquitination level were measured. db/db mice were injected with NaHS (39 μmol·kg-1 ) for 20 weeks. Echocardiography, cardiac ultrastructure, cystathionine-γ-lyase, cardiac structure proteins expression, and S-sulfhydration production were measured.Key Results: H2 S levels and cystathionine-γ-lyase protein expression in myocardium were decreased in db/db mice. Exogenous H2 S reversed endoplasmic reticulum stress, including impairment of the function of cardiomyocytes and structural damage in db/db mice. Exogenous H2 S could suppress the levels of myosin heavy chain 6 and myosin light chain 2 ubiquitination in cardiac tissues of db/db mice, and MuRF1 was modified by S-sulfhydration, following treatment with exogenous H2 S, to reduce the interaction between MuRF1 and myosin heavy chain 6 and myosin light chain 2.Conclusions and Implications: Our findings suggest that H2 S regulates MuRF1 S-sulfhydration at Cys44 to prevent myocardial degradation in the cardiac tissues of db/db mice.Linked Articles: This article is part of a themed section on Hydrogen Sulfide in Biology & Medicine. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.4/issuetoc. [ABSTRACT FROM AUTHOR]

Hydrogen sulfide (H2S) is involved in diverse physiological functions, such as anti-hypertension, anti-proliferation, regulating ATP synthesis, and reactive oxygen species production. Sirtuin 3 (SIRT3) is a NAD+-dependent deacetylase that regulates mitochondrial energy metabolism. The role of H2S in energy metabolism in diabetic cardiomyopathy (DCM) may be related to regulate SIRT3 expression; however, this role remains to be elucidated. We hypothesized that exogenous H2S could switch cardiac energy metabolic substrate preference by lysine acetylation through promoting the expression of SIRT3 in cardiac tissue of db/db mice. Db/db mice, neonatal rat cardiomyocytes, and H9c2 cell line with the treatment of high glucose, oleate, and palmitate were used as animal and cellular models of type 2 diabetes. Using LC-MS/MS, we identified 76 proteins that increased acetylation, including 8 enzymes related to fatty acid β-oxidation and 7 enzymes of the tricarboxylic acid (TCA) cycle in the db/db mice hearts compared to those with the treatment of NaHS. Exogenous H2S restored the expression of NAMPT and the ratio of NAD+/NADH enhanced the expression and activity of SIRT3. As a result of activation of SIRT3, the acetylation level and activity of fatty acid β-oxidation enzyme LCAD and the acetylation of glucose oxidation enzymes PDH, IDH2, and CS were reduced which resulted in activation of PDH, IDH2, and CS. Our finding suggested that H2S induced a switch in cardiac energy substrate utilization from fatty acid β-oxidation to glucose oxidation in DCM through regulating SIRT3 pathway.H2S regulated the acetylation level and activities of enzymes in fatty acid oxidation and glucose oxidation in cardiac tissues of db/db mice.Exogenous H2S decreased mitochondrial acetylation level through upregulating the expression and activity of SIRT3 in vivo and in vitro.H2S induced a switch in cardiac energy substrate utilization from fatty acid oxidation to glucose.H2S regulated the acetylation level and activities of enzymes in fatty acid oxidation and glucose oxidation in cardiac tissues of db/db mice.Exogenous H2S decreased mitochondrial acetylation level through upregulating the expression and activity of SIRT3 in vivo and in vitro.H2S induced a switch in cardiac energy substrate utilization from fatty acid oxidation to glucose.Hydrogen sulfide (H2S) is involved in diverse physiological functions, such as anti-hypertension, anti-proliferation, regulating ATP synthesis, and reactive oxygen species production. Sirtuin 3 (SIRT3) is a NAD+-dependent deacetylase that regulates mitochondrial energy metabolism. The role of H2S in energy metabolism in diabetic cardiomyopathy (DCM) may be related to regulate SIRT3 expression; however, this role remains to be elucidated. We hypothesized that exogenous H2S could switch cardiac energy metabolic substrate preference by lysine acetylation through promoting the expression of SIRT3 in cardiac tissue of db/db mice. Db/db mice, neonatal rat cardiomyocytes, and H9c2 cell line with the treatment of high glucose, oleate, and palmitate were used as animal and cellular models of type 2 diabetes. Using LC-MS/MS, we identified 76 proteins that increased acetylation, including 8 enzymes related to fatty acid β-oxidation and 7 enzymes of the tricarboxylic acid (TCA) cycle in the db/db mice hearts compared to those with the treatment of NaHS. Exogenous H2S restored the expression of NAMPT and the ratio of NAD+/NADH enhanced the expression and activity of SIRT3. As a result of activation of SIRT3, the acetylation level and activity of fatty acid β-oxidation enzyme LCAD and the acetylation of glucose oxidation enzymes PDH, IDH2, and CS were reduced which resulted in activation of PDH, IDH2, and CS. Our finding suggested that H2S induced a switch in cardiac energy substrate utilization from fatty acid β-oxidation to glucose oxidation in DCM through regulating SIRT3 pathway.H2S regulated the acetylation level and activities of enzymes in fatty acid oxidation and glucose oxidation in cardiac tissues of db/db mice.Exogenous H2S decreased mitochondrial acetylation level through upregulating the expression and activity of SIRT3 in vivo and in vitro.H2S induced a switch in cardiac energy substrate utilization from fatty acid oxidation to glucose.H2S regulated the acetylation level and activities of enzymes in fatty acid oxidation and glucose oxidation in cardiac tissues of db/db mice.Exogenous H2S decreased mitochondrial acetylation level through upregulating the expression and activity of SIRT3 in vivo and in vitro.H2S induced a switch in cardiac energy substrate utilization from fatty acid oxidation to glucose.Hydrogen sulfide (H2S) is involved in diverse physiological functions, such as anti-hypertension, anti-proliferation, regulating ATP synthesis, and reactive oxygen species production. Sirtuin 3 (SIRT3) is a NAD+-dependent deacetylase that regulates mitochondrial energy metabolism. The role of H2S in energy metabolism in diabetic cardiomyopathy (DCM) may be related to regulate SIRT3 expression; however, this role remains to be elucidated. We hypothesized that exogenous H2S could switch cardiac energy metabolic substrate preference by lysine acetylation through promoting the expression of SIRT3 in cardiac tissue of db/db mice. Db/db mice, neonatal rat cardiomyocytes, and H9c2 cell line with the treatment of high glucose, oleate, and palmitate were used as animal and cellular models of type 2 diabetes. Using LC-MS/MS, we identified 76 proteins that increased acetylation, including 8 enzymes related to fatty acid β-oxidation and 7 enzymes of the tricarboxylic acid (TCA) cycle in the db/db mice hearts compared to those with the treatment of NaHS. Exogenous H2S restored the expression of NAMPT and the ratio of NAD+/NADH enhanced the expression and activity of SIRT3. As a result of activation of SIRT3, the acetylation level and activity of fatty acid β-oxidation enzyme LCAD and the acetylation of glucose oxidation enzymes PDH, IDH2, and CS were reduced which resulted in activation of PDH, IDH2, and CS. Our finding suggested that H2S induced a switch in cardiac energy substrate utilization from fatty acid β-oxidation to glucose oxidation in DCM through regulating SIRT3 pathway.H2S regulated the acetylation level and activities of enzymes in fatty acid oxidation and glucose oxidation in cardiac tissues of db/db mice.Exogenous H2S decreased mitochondrial acetylation level through upregulating the expression and activity of SIRT3 in vivo and in vitro.H2S induced a switch in cardiac energy substrate utilization from fatty acid oxidation to glucose.H2S regulated the acetylation level and activities of enzymes in fatty acid oxidation and glucose oxidation in cardiac tissues of db/db mice.Exogenous H2S decreased mitochondrial acetylation level through upregulating the expression and activity of SIRT3 in vivo and in vitro.H2S induced a switch in cardiac energy substrate utilization from fatty acid oxidation to glucose.Hydrogen sulfide (H2S) is involved in diverse physiological functions, such as anti-hypertension, anti-proliferation, regulating ATP synthesis, and reactive oxygen species production. Sirtuin 3 (SIRT3) is a NAD+-dependent deacetylase that regulates mitochondrial energy metabolism. The role of H2S in energy metabolism in diabetic cardiomyopathy (DCM) may be related to regulate SIRT3 expression; however, this role remains to be elucidated. We hypothesized that exogenous H2S could switch cardiac energy metabolic substrate preference by lysine acetylation through promoting the expression of SIRT3 in cardiac tissue of db/db mice. Db/db mice, neonatal rat cardiomyocytes, and H9c2 cell line with the treatment of high glucose, oleate, and palmitate were used as animal and cellular models of type 2 diabetes. Using LC-MS/MS, we identified 76 proteins that increased acetylation, including 8 enzymes related to fatty acid β-oxidation and 7 enzymes of the tricarboxylic acid (TCA) cycle in the db/db mice hearts compared to those with the treatment of NaHS. Exogenous H2S restored the expression of NAMPT and the ratio of NAD+/NADH enhanced the expression and activity of SIRT3. As a result of activation of SIRT3, the acetylation level and activity of fatty acid β-oxidation enzyme LCAD and the acetylation of glucose oxidation enzymes PDH, IDH2, and CS were reduced which resulted in activation of PDH, IDH2, and CS. Our finding suggested that H2S induced a switch in cardiac energy substrate utilization from fatty acid β-oxidation to glucose oxidation in DCM through regulating SIRT3 pathway.H2S regulated the acetylation level and activities of enzymes in fatty acid oxidation and glucose oxidation in cardiac tissues of db/db mice.Exogenous H2S decreased mitochondrial acetylation level through upregulating the expression and activity of SIRT3 in vivo and in vitro.H2S induced a switch in cardiac energy substrate utilization from fatty acid oxidation to glucose.H2S regulated the acetylation level and activities of enzymes in fatty acid oxidation and glucose oxidation in cardiac tissues of db/db mice.Exogenous H2S decreased mitochondrial acetylation level through upregulating the expression and activity of SIRT3 in vivo and in vitro.H2S induced a switch in cardiac energy substrate utilization from fatty acid oxidation to glucose.Hydrogen sulfide (H2S) is involved in diverse physiological functions, such as anti-hypertension, anti-proliferation, regulating ATP synthesis, and reactive oxygen species production. Sirtuin 3 (SIRT3) is a NAD+-dependent deacetylase that regulates mitochondrial energy metabolism. The role of H2S in energy metabolism in diabetic cardiomyopathy (DCM) may be related to regulate SIRT3 expression; however, this role remains to be elucidated. We hypothesized that exogenous H2S could switch cardiac energy metabolic substrate preference by lysine acetylation through promoting the expression of SIRT3 in cardiac tissue of db/db mice. Db/db mice, neonatal rat cardiomyocytes, and H9c2 cell line with the treatment of high glucose, oleate, and palmitate were used as animal and cellular models of type 2 diabetes. Using LC-MS/MS, we identified 76 proteins that increased acetylation, including 8 enzymes related to fatty acid β-oxidation and 7 enzymes of the tricarboxylic acid (TCA) cycle in the db/db mice hearts compared to those with the treatment of NaHS. Exogenous H2S restored the expression of NAMPT and the ratio of NAD+/NADH enhanced the expression and activity of SIRT3. As a result of activation of SIRT3, the acetylation level and activity of fatty acid β-oxidation enzyme LCAD and the acetylation of glucose oxidation enzymes PDH, IDH2, and CS were reduced which resulted in activation of PDH, IDH2, and CS. Our finding suggested that H2S induced a switch in cardiac energy substrate utilization from fatty acid β-oxidation to glucose oxidation in DCM through regulating SIRT3 pathway.H2S regulated the acetylation level and activities of enzymes in fatty acid oxidation and glucose oxidation in cardiac tissues of db/db mice.Exogenous H2S decreased mitochondrial acetylation level through upregulating the expression and activity of SIRT3 in vivo and in vitro.H2S induced a switch in cardiac energy substrate utilization from fatty acid oxidation to glucose.H2S regulated the acetylation level and activities of enzymes in fatty acid oxidation and glucose oxidation in cardiac tissues of db/db mice.Exogenous H2S decreased mitochondrial acetylation level through upregulating the expression and activity of SIRT3 in vivo and in vitro.H2S induced a switch in cardiac energy substrate utilization from fatty acid oxidation to glucose.Hydrogen sulfide (H2S) is involved in diverse physiological functions, such as anti-hypertension, anti-proliferation, regulating ATP synthesis, and reactive oxygen species production. Sirtuin 3 (SIRT3) is a NAD+-dependent deacetylase that regulates mitochondrial energy metabolism. The role of H2S in energy metabolism in diabetic cardiomyopathy (DCM) may be related to regulate SIRT3 expression; however, this role remains to be elucidated. We hypothesized that exogenous H2S could switch cardiac energy metabolic substrate preference by lysine acetylation through promoting the expression of SIRT3 in cardiac tissue of db/db mice. Db/db mice, neonatal rat cardiomyocytes, and H9c2 cell line with the treatment of high glucose, oleate, and palmitate were used as animal and cellular models of type 2 diabetes. Using LC-MS/MS, we identified 76 proteins that increased acetylation, including 8 enzymes related to fatty acid β-oxidation and 7 enzymes of the tricarboxylic acid (TCA) cycle in the db/db mice hearts compared to those with the treatment of NaHS. Exogenous H2S restored the expression of NAMPT and the ratio of NAD+/NADH enhanced the expression and activity of SIRT3. As a result of activation of SIRT3, the acetylation level and activity of fatty acid β-oxidation enzyme LCAD and the acetylation of glucose oxidation enzymes PDH, IDH2, and CS were reduced which resulted in activation of PDH, IDH2, and CS. Our finding suggested that H2S induced a switch in cardiac energy substrate utilization from fatty acid β-oxidation to glucose oxidation in DCM through regulating SIRT3 pathway.H2S regulated the acetylation level and activities of enzymes in fatty acid oxidation and glucose oxidation in cardiac tissues of db/db mice.Exogenous H2S decreased mitochondrial acetylation level through upregulating the expression and activity of SIRT3 in vivo and in vitro.H2S induced a switch in cardiac energy substrate utilization from fatty acid oxidation to glucose.H2S regulated the acetylation level and activities of enzymes in fatty acid oxidation and glucose oxidation in cardiac tissues of db/db mice.Exogenous H2S decreased mitochondrial acetylation level through upregulating the expression and activity of SIRT3 in vivo and in vitro.H2S induced a switch in cardiac energy substrate utilization from fatty acid oxidation to glucose.Hydrogen sulfide (H2S) is involved in diverse physiological functions, such as anti-hypertension, anti-proliferation, regulating ATP synthesis, and reactive oxygen species production. Sirtuin 3 (SIRT3) is a NAD+-dependent deacetylase that regulates mitochondrial energy metabolism. The role of H2S in energy metabolism in diabetic cardiomyopathy (DCM) may be related to regulate SIRT3 expression; however, this role remains to be elucidated. We hypothesized that exogenous H2S could switch cardiac energy metabolic substrate preference by lysine acetylation through promoting the expression of SIRT3 in cardiac tissue of db/db mice. Db/db mice, neonatal rat cardiomyocytes, and H9c2 cell line with the treatment of high glucose, oleate, and palmitate were used as animal and cellular models of type 2 diabetes. Using LC-MS/MS, we identified 76 proteins that increased acetylation, including 8 enzymes related to fatty acid β-oxidation and 7 enzymes of the tricarboxylic acid (TCA) cycle in the db/db mice hearts compared to those with the treatment of NaHS. Exogenous H2S restored the expression of NAMPT and the ratio of NAD+/NADH enhanced the expression and activity of SIRT3. As a result of activation of SIRT3, the acetylation level and activity of fatty acid β-oxidation enzyme LCAD and the acetylation of glucose oxidation enzymes PDH, IDH2, and CS were reduced which resulted in activation of PDH, IDH2, and CS. Our finding suggested that H2S induced a switch in cardiac energy substrate utilization from fatty acid β-oxidation to glucose oxidation in DCM through regulating SIRT3 pathway.H2S regulated the acetylation level and activities of enzymes in fatty acid oxidation and glucose oxidation in cardiac tissues of db/db mice.Exogenous H2S decreased mitochondrial acetylation level through upregulating the expression and activity of SIRT3 in vivo and in vitro.H2S induced a switch in cardiac energy substrate utilization from fatty acid oxidation to glucose.H2S regulated the acetylation level and activities of enzymes in fatty acid oxidation and glucose oxidation in cardiac tissues of db/db mice.Exogenous H2S decreased mitochondrial acetylation level through upregulating the expression and activity of SIRT3 in vivo and in vitro.H2S induced a switch in cardiac energy substrate utilization from fatty acid oxidation to glucose.Hydrogen sulfide (H2S) is involved in diverse physiological functions, such as anti-hypertension, anti-proliferation, regulating ATP synthesis, and reactive oxygen species production. Sirtuin 3 (SIRT3) is a NAD+-dependent deacetylase that regulates mitochondrial energy metabolism. The role of H2S in energy metabolism in diabetic cardiomyopathy (DCM) may be related to regulate SIRT3 expression; however, this role remains to be elucidated. We hypothesized that exogenous H2S could switch cardiac energy metabolic substrate preference by lysine acetylation through promoting the expression of SIRT3 in cardiac tissue of db/db mice. Db/db mice, neonatal rat cardiomyocytes, and H9c2 cell line with the treatment of high glucose, oleate, and palmitate were used as animal and cellular models of type 2 diabetes. Using LC-MS/MS, we identified 76 proteins that increased acetylation, including 8 enzymes related to fatty acid β-oxidation and 7 enzymes of the tricarboxylic acid (TCA) cycle in the db/db mice hearts compared to those with the treatment of NaHS. Exogenous H2S restored the expression of NAMPT and the ratio of NAD+/NADH enhanced the expression and activity of SIRT3. As a result of activation of SIRT3, the acetylation level and activity of fatty acid β-oxidation enzyme LCAD and the acetylation of glucose oxidation enzymes PDH, IDH2, and CS were reduced which resulted in activation of PDH, IDH2, and CS. Our finding suggested that H2S induced a switch in cardiac energy substrate utilization from fatty acid β-oxidation to glucose oxidation in DCM through regulating SIRT3 pathway.H2S regulated the acetylation level and activities of enzymes in fatty acid oxidation and glucose oxidation in cardiac tissues of db/db mice.Exogenous H2S decreased mitochondrial acetylation level through upregulating the expression and activity of SIRT3 in vivo and in vitro.H2S induced a switch in cardiac energy substrate utilization from fatty acid oxidation to glucose.H2S regulated the acetylation level and activities of enzymes in fatty acid oxidation and glucose oxidation in cardiac tissues of db/db mice.Exogenous H2S decreased mitochondrial acetylation level through upregulating the expression and activity of SIRT3 in vivo and in vitro.H2S induced a switch in cardiac energy substrate utilization from fatty acid oxidation to glucose.Hydrogen sulfide (H2S) is involved in diverse physiological functions, such as anti-hypertension, anti-proliferation, regulating ATP synthesis, and reactive oxygen species production. Sirtuin 3 (SIRT3) is a NAD+-dependent deacetylase that regulates mitochondrial energy metabolism. The role of H2S in energy metabolism in diabetic cardiomyopathy (DCM) may be related to regulate SIRT3 expression; however, this role remains to be elucidated. We hypothesized that exogenous H2S could switch cardiac energy metabolic substrate preference by lysine acetylation through promoting the expression of SIRT3 in cardiac tissue of db/db mice. Db/db mice, neonatal rat cardiomyocytes, and H9c2 cell line with the treatment of high glucose, oleate, and palmitate were used as animal and cellular models of type 2 diabetes. Using LC-MS/MS, we identified 76 proteins that increased acetylation, including 8 enzymes related to fatty acid β-oxidation and 7 enzymes of the tricarboxylic acid (TCA) cycle in the db/db mice hearts compared to those with the treatment of NaHS. Exogenous H2S restored the expression of NAMPT and the ratio of NAD+/NADH enhanced the expression and activity of SIRT3. As a result of activation of SIRT3, the acetylation level and activity of fatty acid β-oxidation enzyme LCAD and the acetylation of glucose oxidation enzymes PDH, IDH2, and CS were reduced which resulted in activation of PDH, IDH2, and CS. Our finding suggested that H2S induced a switch in cardiac energy substrate utilization from fatty acid β-oxidation to glucose oxidation in DCM through regulating SIRT3 pathway.H2S regulated the acetylation level and activities of enzymes in fatty acid oxidation and glucose oxidation in cardiac tissues of db/db mice.Exogenous H2S decreased mitochondrial acetylation level through upregulating the expression and activity of SIRT3 in vivo and in vitro.H2S induced a switch in cardiac energy substrate utilization from fatty acid oxidation to glucose.H2S regulated the acetylation level and activities of enzymes in fatty acid oxidation and glucose oxidation in cardiac tissues of db/db mice.Exogenous H2S decreased mitochondrial acetylation level through upregulating the expression and activity of SIRT3 in vivo and in vitro.H2S induced a switch in cardiac energy substrate utilization from fatty acid oxidation to glucose.Hydrogen sulfide (H2S) is involved in diverse physiological functions, such as anti-hypertension, anti-proliferation, regulating ATP synthesis, and reactive oxygen species production. Sirtuin 3 (SIRT3) is a NAD+-dependent deacetylase that regulates mitochondrial energy metabolism. The role of H2S in energy metabolism in diabetic cardiomyopathy (DCM) may be related to regulate SIRT3 expression; however, this role remains to be elucidated. We hypothesized that exogenous H2S could switch cardiac energy metabolic substrate preference by lysine acetylation through promoting the expression of SIRT3 in cardiac tissue of db/db mice. Db/db mice, neonatal rat cardiomyocytes, and H9c2 cell line with the treatment of high glucose, oleate, and palmitate were used as animal and cellular models of type 2 diabetes. Using LC-MS/MS, we identified 76 proteins that increased acetylation, including 8 enzymes related to fatty acid β-oxidation and 7 enzymes of the tricarboxylic acid (TCA) cycle in the db/db mice hearts compared to those with the treatment of NaHS. Exogenous H2S restored the expression of NAMPT and the ratio of NAD+/NADH enhanced the expression and activity of SIRT3. As a result of activation of SIRT3, the acetylation level and activity of fatty acid β-oxidation enzyme LCAD and the acetylation of glucose oxidation enzymes PDH, IDH2, and CS were reduced which resulted in activation of PDH, IDH2, and CS. Our finding suggested that H2S induced a switch in cardiac energy substrate utilization from fatty acid β-oxidation to glucose oxidation in DCM through regulating SIRT3 pathway.H2S regulated the acetylation level and activities of enzymes in fatty acid oxidation and glucose oxidation in cardiac tissues of db/db mice.Exogenous H2S decreased mitochondrial acetylation level through upregulating the expression and activity of SIRT3 in vivo and in vitro.H2S induced a switch in cardiac energy substrate utilization from fatty acid oxidation to glucose.H2S regulated the acetylation level and activities of enzymes in fatty acid oxidation and glucose oxidation in cardiac tissues of db/db mice.Exogenous H2S decreased mitochondrial acetylation level through upregulating the expression and activity of SIRT3 in vivo and in vitro.H2S induced a switch in cardiac energy substrate utilization from fatty acid oxidation to glucose.Hydrogen sulfide (H2S) is involved in diverse physiological functions, such as anti-hypertension, anti-proliferation, regulating ATP synthesis, and reactive oxygen species production. Sirtuin 3 (SIRT3) is a NAD+-dependent deacetylase that regulates mitochondrial energy metabolism. The role of H2S in energy metabolism in diabetic cardiomyopathy (DCM) may be related to regulate SIRT3 expression; however, this role remains to be elucidated. We hypothesized that exogenous H2S could switch cardiac energy metabolic substrate preference by lysine acetylation through promoting the expression of SIRT3 in cardiac tissue of db/db mice. Db/db mice, neonatal rat cardiomyocytes, and H9c2 cell line with the treatment of high glucose, oleate, and palmitate were used as animal and cellular models of type 2 diabetes. Using LC-MS/MS, we identified 76 proteins that increased acetylation, including 8 enzymes related to fatty acid β-oxidation and 7 enzymes of the tricarboxylic acid (TCA) cycle in the db/db mice hearts compared to those with the treatment of NaHS. Exogenous H2S restored the expression of NAMPT and the ratio of NAD+/NADH enhanced the expression and activity of SIRT3. As a result of activation of SIRT3, the acetylation level and activity of fatty acid β-oxidation enzyme LCAD and the acetylation of glucose oxidation enzymes PDH, IDH2, and CS were reduced which resulted in activation of PDH, IDH2, and CS. Our finding suggested that H2S induced a switch in cardiac energy substrate utilization from fatty acid β-oxidation to glucose oxidation in DCM through regulating SIRT3 pathway.H2S regulated the acetylation level and activities of enzymes in fatty acid oxidation and glucose oxidation in cardiac tissues of db/db mice.Exogenous H2S decreased mitochondrial acetylation level through upregulating the expression and activity of SIRT3 in vivo and in vitro.H2S induced a switch in cardiac energy substrate utilization from fatty acid oxidation to glucose.H2S regulated the acetylation level and activities of enzymes in fatty acid oxidation and glucose oxidation in cardiac tissues of db/db mice.Exogenous H2S decreased mitochondrial acetylation level through upregulating the expression and activity of SIRT3 in vivo and in vitro.H2S induced a switch in cardiac energy substrate utilization from fatty acid oxidation to glucose.Hydrogen sulfide (H2S) is involved in diverse physiological functions, such as anti-hypertension, anti-proliferation, regulating ATP synthesis, and reactive oxygen species production. Sirtuin 3 (SIRT3) is a NAD+-dependent deacetylase that regulates mitochondrial energy metabolism. The role of H2S in energy metabolism in diabetic cardiomyopathy (DCM) may be related to regulate SIRT3 expression; however, this role remains to be elucidated. We hypothesized that exogenous H2S could switch cardiac energy metabolic substrate preference by lysine acetylation through promoting the expression of SIRT3 in cardiac tissue of db/db mice. Db/db mice, neonatal rat cardiomyocytes, and H9c2 cell line with the treatment of high glucose, oleate, and palmitate were used as animal and cellular models of type 2 diabetes. Using LC-MS/MS, we identified 76 proteins that increased acetylation, including 8 enzymes related to fatty acid β-oxidation and 7 enzymes of the tricarboxylic acid (TCA) cycle in the db/db mice hearts compared to those with the treatment of NaHS. Exogenous H2S restored the expression of NAMPT and the ratio of NAD+/NADH enhanced the expression and activity of SIRT3. As a result of activation of SIRT3, the acetylation level and activity of fatty acid β-oxidation enzyme LCAD and the acetylation of glucose oxidation enzymes PDH, IDH2, and CS were reduced which resulted in activation of PDH, IDH2, and CS. Our finding suggested that H2S induced a switch in cardiac energy substrate utilization from fatty acid β-oxidation to glucose oxidation in DCM through regulating SIRT3 pathway.H2S regulated the acetylation level and activities of enzymes in fatty acid oxidation and glucose oxidation in cardiac tissues of db/db mice.Exogenous H2S decreased mitochondrial acetylation level through upregulating the expression and activity of SIRT3 in vivo and in vitro.H2S induced a switch in cardiac energy substrate utilization from fatty acid oxidation to glucose.H2S regulated the acetylation level and activities of enzymes in fatty acid oxidation and glucose oxidation in cardiac tissues of db/db mice.Exogenous H2S decreased mitochondrial acetylation level through upregulating the expression and activity of SIRT3 in vivo and in vitro.H2S induced a switch in cardiac energy substrate utilization from fatty acid oxidation to glucose.Hydrogen sulfide (H2S) is involved in diverse physiological functions, such as anti-hypertension, anti-proliferation, regulating ATP synthesis, and reactive oxygen species production. Sirtuin 3 (SIRT3) is a NAD+-dependent deacetylase that regulates mitochondrial energy metabolism. The role of H2S in energy metabolism in diabetic cardiomyopathy (DCM) may be related to regulate SIRT3 expression; however, this role remains to be elucidated. We hypothesized that exogenous H2S could switch cardiac energy metabolic substrate preference by lysine acetylation through promoting the expression of SIRT3 in cardiac tissue of db/db mice. Db/db mice, neonatal rat cardiomyocytes, and H9c2 cell line with the treatment of high glucose, oleate, and palmitate were used as animal and cellular models of type 2 diabetes. Using LC-MS/MS, we identified 76 proteins that increased acetylation, including 8 enzymes related to fatty acid β-oxidation and 7 enzymes of the tricarboxylic acid (TCA) cycle in the db/db mice hearts compared to those with the treatment of NaHS. Exogenous H2S restored the expression of NAMPT and the ratio of NAD+/NADH enhanced the expression and activity of SIRT3. As a result of activation of SIRT3, the acetylation level and activity of fatty acid β-oxidation enzyme LCAD and the acetylation of glucose oxidation enzymes PDH, IDH2, and CS were reduced which resulted in activation of PDH, IDH2, and CS. Our finding suggested that H2S induced a switch in cardiac energy substrate utilization from fatty acid β-oxidation to glucose oxidation in DCM through regulating SIRT3 pathway.H2S regulated the acetylation level and activities of enzymes in fatty acid oxidation and glucose oxidation in cardiac tissues of db/db mice.Exogenous H2S decreased mitochondrial acetylation level through upregulating the expression and activity of SIRT3 in vivo and in vitro.H2S induced a switch in cardiac energy substrate utilization from fatty acid oxidation to glucose.H2S regulated the acetylation level and activities of enzymes in fatty acid oxidation and glucose oxidation in cardiac tissues of db/db mice.Exogenous H2S decreased mitochondrial acetylation level through upregulating the expression and activity of SIRT3 in vivo and in vitro.H2S induced a switch in cardiac energy substrate utilization from fatty acid oxidation to glucose.Hydrogen sulfide (H2S) is involved in diverse physiological functions, such as anti-hypertension, anti-proliferation, regulating ATP synthesis, and reactive oxygen species production. Sirtuin 3 (SIRT3) is a NAD+-dependent deacetylase that regulates mitochondrial energy metabolism. The role of H2S in energy metabolism in diabetic cardiomyopathy (DCM) may be related to regulate SIRT3 expression; however, this role remains to be elucidated. We hypothesized that exogenous H2S could switch cardiac energy metabolic substrate preference by lysine acetylation through promoting the expression of SIRT3 in cardiac tissue of db/db mice. Db/db mice, neonatal rat cardiomyocytes, and H9c2 cell line with the treatment of high glucose, oleate, and palmitate were used as animal and cellular models of type 2 diabetes. Using LC-MS/MS, we identified 76 proteins that increased acetylation, including 8 enzymes related to fatty acid β-oxidation and 7 enzymes of the tricarboxylic acid (TCA) cycle in the db/db mice hearts compared to those with the treatment of NaHS. Exogenous H2S restored the expression of NAMPT and the ratio of NAD+/NADH enhanced the expression and activity of SIRT3. As a result of activation of SIRT3, the acetylation level and activity of fatty acid β-oxidation enzyme LCAD and the acetylation of glucose oxidation enzymes PDH, IDH2, and CS were reduced which resulted in activation of PDH, IDH2, and CS. Our finding suggested that H2S induced a switch in cardiac energy substrate utilization from fatty acid β-oxidation to glucose oxidation in DCM through regulating SIRT3 pathway.H2S regulated the acetylation level and activities of enzymes in fatty acid oxidation and glucose oxidation in cardiac tissues of db/db mice.Exogenous H2S decreased mitochondrial acetylation level through upregulating the expression and activity of SIRT3 in vivo and in vitro.H2S induced a switch in cardiac energy substrate utilization from fatty acid oxidation to glucose.H2S regulated the acetylation level and activities of enzymes in fatty acid oxidation and glucose oxidation in cardiac tissues of db/db mice.Exogenous H2S decreased mitochondrial acetylation level through upregulating the expression and activity of SIRT3 in vivo and in vitro.H2S induced a switch in cardiac energy substrate utilization from fatty acid oxidation to glucose.Hydrogen sulfide (H2S) is involved in diverse physiological functions, such as anti-hypertension, anti-proliferation, regulating ATP synthesis, and reactive oxygen species production. Sirtuin 3 (SIRT3) is a NAD+-dependent deacetylase that regulates mitochondrial energy metabolism. The role of H2S in energy metabolism in diabetic cardiomyopathy (DCM) may be related to regulate SIRT3 expression; however, this role remains to be elucidated. We hypothesized that exogenous H2S could switch cardiac energy metabolic substrate preference by lysine acetylation through promoting the expression of SIRT3 in cardiac tissue of db/db mice. Db/db mice, neonatal rat cardiomyocytes, and H9c2 cell line with the treatment of high glucose, oleate, and palmitate were used as animal and cellular models of type 2 diabetes. Using LC-MS/MS, we identified 76 proteins that increased acetylation, including 8 enzymes related to fatty acid β-oxidation and 7 enzymes of the tricarboxylic acid (TCA) cycle in the db/db mice hearts compared to those with the treatment of NaHS. Exogenous H2S restored the expression of NAMPT and the ratio of NAD+/NADH enhanced the expression and activity of SIRT3. As a result of activation of SIRT3, the acetylation level and activity of fatty acid β-oxidation enzyme LCAD and the acetylation of glucose oxidation enzymes PDH, IDH2, and CS were reduced which resulted in activation of PDH, IDH2, and CS. Our finding suggested that H2S induced a switch in cardiac energy substrate utilization from fatty acid β-oxidation to glucose oxidation in DCM through regulating SIRT3 pathway.H2S regulated the acetylation level and activities of enzymes in fatty acid oxidation and glucose oxidation in cardiac tissues of db/db mice.Exogenous H2S decreased mitochondrial acetylation level through upregulating the expression and activity of SIRT3 in vivo and in vitro.H2S induced a switch in cardiac energy substrate utilization from fatty acid oxidation to glucose.H2S regulated the acetylation level and activities of enzymes in fatty acid oxidation and glucose oxidation in cardiac tissues of db/db mice.Exogenous H2S decreased mitochondrial acetylation level through upregulating the expression and activity of SIRT3 in vivo and in vitro.H2S induced a switch in cardiac energy substrate utilization from fatty acid oxidation to glucose.Hydrogen sulfide (H2S) is involved in diverse physiological functions, such as anti-hypertension, anti-proliferation, regulating ATP synthesis, and reactive oxygen species production. Sirtuin 3 (SIRT3) is a NAD+-dependent deacetylase that regulates mitochondrial energy metabolism. The role of H2S in energy metabolism in diabetic cardiomyopathy (DCM) may be related to regulate SIRT3 expression; however, this role remains to be elucidated. We hypothesized that exogenous H2S could switch cardiac energy metabolic substrate preference by lysine acetylation through promoting the expression of SIRT3 in cardiac tissue of db/db mice. Db/db mice, neonatal rat cardiomyocytes, and H9c2 cell line with the treatment of high glucose, oleate, and palmitate were used as animal and cellular models of type 2 diabetes. Using LC-MS/MS, we identified 76 proteins that increased acetylation, including 8 enzymes related to fatty acid β-oxidation and 7 enzymes of the tricarboxylic acid (TCA) cycle in the db/db mice hearts compared to those with the treatment of NaHS. Exogenous H2S restored the expression of NAMPT and the ratio of NAD+/NADH enhanced the expression and activity of SIRT3. As a result of activation of SIRT3, the acetylation level and activity of fatty acid β-oxidation enzyme LCAD and the acetylation of glucose oxidation enzymes PDH, IDH2, and CS were reduced which resulted in activation of PDH, IDH2, and CS. Our finding suggested that H2S induced a switch in cardiac energy substrate utilization from fatty acid β-oxidation to glucose oxidation in DCM through regulating SIRT3 pathway.H2S regulated the acetylation level and activities of enzymes in fatty acid oxidation and glucose oxidation in cardiac tissues of db/db mice.Exogenous H2S decreased mitochondrial acetylation level through upregulating the expression and activity of SIRT3 in vivo and in vitro.H2S induced a switch in cardiac energy substrate utilization from fatty acid oxidation to glucose.H2S regulated the acetylation level and activities of enzymes in fatty acid oxidation and glucose oxidation in cardiac tissues of db/db mice.Exogenous H2S decreased mitochondrial acetylation level through upregulating the expression and activity of SIRT3 in vivo and in vitro.H2S induced a switch in cardiac energy substrate utilization from fatty acid oxidation to glucose.Hydrogen sulfide (H2S) is involved in diverse physiological functions, such as anti-hypertension, anti-proliferation, regulating ATP synthesis, and reactive oxygen species production. Sirtuin 3 (SIRT3) is a NAD+-dependent deacetylase that regulates mitochondrial energy metabolism. The role of H2S in energy metabolism in diabetic cardiomyopathy (DCM) may be related to regulate SIRT3 expression; however, this role remains to be elucidated. We hypothesized that exogenous H2S could switch cardiac energy metabolic substrate preference by lysine acetylation through promoting the expression of SIRT3 in cardiac tissue of db/db mice. Db/db mice, neonatal rat cardiomyocytes, and H9c2 cell line with the treatment of high glucose, oleate, and palmitate were used as animal and cellular models of type 2 diabetes. Using LC-MS/MS, we identified 76 proteins that increased acetylation, including 8 enzymes related to fatty acid β-oxidation and 7 enzymes of the tricarboxylic acid (TCA) cycle in the db/db mice hearts compared to those with the treatment of NaHS. Exogenous H2S restored the expression of NAMPT and the ratio of NAD+/NADH enhanced the expression and activity of SIRT3. As a result of activation of SIRT3, the acetylation level and activity of fatty acid β-oxidation enzyme LCAD and the acetylation of glucose oxidation enzymes PDH, IDH2, and CS were reduced which resulted in activation of PDH, IDH2, and CS. Our finding suggested that H2S induced a switch in cardiac energy substrate utilization from fatty acid β-oxidation to glucose oxidation in DCM through regulating SIRT3 pathway.H2S regulated the acetylation level and activities of enzymes in fatty acid oxidation and glucose oxidation in cardiac tissues of db/db mice.Exogenous H2S decreased mitochondrial acetylation level through upregulating the expression and activity of SIRT3 in vivo and in vitro.H2S induced a switch in cardiac energy substrate utilization from fatty acid oxidation to glucose.H2S regulated the acetylation level and activities of enzymes in fatty acid oxidation and glucose oxidation in cardiac tissues of db/db mice.Exogenous H2S decreased mitochondrial acetylation level through upregulating the expression and activity of SIRT3 in vivo and in vitro.H2S induced a switch in cardiac energy substrate utilization from fatty acid oxidation to glucose.Hydrogen sulfide (H2S) is involved in diverse physiological functions, such as anti-hypertension, anti-proliferation, regulating ATP synthesis, and reactive oxygen species production. Sirtuin 3 (SIRT3) is a NAD+-dependent deacetylase that regulates mitochondrial energy metabolism. The role of H2S in energy metabolism in diabetic cardiomyopathy (DCM) may be related to regulate SIRT3 expression; however, this role remains to be elucidated. We hypothesized that exogenous H2S could switch cardiac energy metabolic substrate preference by lysine acetylation through promoting the expression of SIRT3 in cardiac tissue of db/db mice. Db/db mice, neonatal rat cardiomyocytes, and H9c2 cell line with the treatment of high glucose, oleate, and palmitate were used as animal and cellular models of type 2 diabetes. Using LC-MS/MS, we identified 76 proteins that increased acetylation, including 8 enzymes related to fatty acid β-oxidation and 7 enzymes of the tricarboxylic acid (TCA) cycle in the db/db mice hearts compared to those with the treatment of NaHS. Exogenous H2S restored the expression of NAMPT and the ratio of NAD+/NADH enhanced the expression and activity of SIRT3. As a result of activation of SIRT3, the acetylation level and activity of fatty acid β-oxidation enzyme LCAD and the acetylation of glucose oxidation enzymes PDH, IDH2, and CS were reduced which resulted in activation of PDH, IDH2, and CS. Our finding suggested that H2S induced a switch in cardiac energy substrate utilization from fatty acid β-oxidation to glucose oxidation in DCM through regulating SIRT3 pathway.H2S regulated the acetylation level and activities of enzymes in fatty acid oxidation and glucose oxidation in cardiac tissues of db/db mice.Exogenous H2S decreased mitochondrial acetylation level through upregulating the expression and activity of SIRT3 in vivo and in vitro.H2S induced a switch in cardiac energy substrate utilization from fatty acid oxidation to glucose.H2S regulated the acetylation level and activities of enzymes in fatty acid oxidation and glucose oxidation in cardiac tissues of db/db mice.Exogenous H2S decreased mitochondrial acetylation level through upregulating the expression and activity of SIRT3 in vivo and in vitro.H2S induced a switch in cardiac energy substrate utilization from fatty acid oxidation to glucose.Hydrogen sulfide (H2S) is involved in diverse physiological functions, such as anti-hypertension, anti-proliferation, regulating ATP synthesis, and reactive oxygen species production. Sirtuin 3 (SIRT3) is a NAD+-dependent deacetylase that regulates mitochondrial energy metabolism. The role of H2S in energy metabolism in diabetic cardiomyopathy (DCM) may be related to regulate SIRT3 expression; however, this role remains to be elucidated. We hypothesized that exogenous H2S could switch cardiac energy metabolic substrate preference by lysine acetylation through promoting the expression of SIRT3 in cardiac tissue of db/db mice. Db/db mice, neonatal rat cardiomyocytes, and H9c2 cell line with the treatment of high glucose, oleate, and palmitate were used as animal and cellular models of type 2 diabetes. Using LC-MS/MS, we identified 76 proteins that increased acetylation, including 8 enzymes related to fatty acid β-oxidation and 7 enzymes of the tricarboxylic acid (TCA) cycle in the db/db mice hearts compared to those with the treatment of NaHS. Exogenous H2S restored the expression of NAMPT and the ratio of NAD+/NADH enhanced the expression and activity of SIRT3. As a result of activation of SIRT3, the acetylation level and activity of fatty acid β-oxidation enzyme LCAD and the acetylation of glucose oxidation enzymes PDH, IDH2, and CS were reduced which resulted in activation of PDH, IDH2, and CS. Our finding suggested that H2S induced a switch in cardiac energy substrate utilization from fatty acid β-oxidation to glucose oxidation in DCM through regulating SIRT3 pathway.H2S regulated the acetylation level and activities of enzymes in fatty acid oxidation and glucose oxidation in cardiac tissues of db/db mice.Exogenous H2S decreased mitochondrial acetylation level through upregulating the expression and activity of SIRT3 in vivo and in vitro.H2S induced a switch in cardiac energy substrate utilization from fatty acid oxidation to glucose.H2S regulated the acetylation level and activities of enzymes in fatty acid oxidation and glucose oxidation in cardiac tissues of db/db mice.Exogenous H2S decreased mitochondrial acetylation level through upregulating the expression and activity of SIRT3 in vivo and in vitro.H2S induced a switch in cardiac energy substrate utilization from fatty acid oxidation to glucose.Hydrogen sulfide (H2S) is involved in diverse physiological functions, such as anti-hypertension, anti-proliferation, regulating ATP synthesis, and reactive oxygen species production. Sirtuin 3 (SIRT3) is a NAD+-dependent deacetylase that regulates mitochondrial energy metabolism. The role of H2S in energy metabolism in diabetic cardiomyopathy (DCM) may be related to regulate SIRT3 expression; however, this role remains to be elucidated. We hypothesized that exogenous H2S could switch cardiac energy metabolic substrate preference by lysine acetylation through promoting the expression of SIRT3 in cardiac tissue of db/db mice. Db/db mice, neonatal rat cardiomyocytes, and H9c2 cell line with the treatment of high glucose, oleate, and palmitate were used as animal and cellular models of type 2 diabetes. Using LC-MS/MS, we identified 76 proteins that increased acetylation, including 8 enzymes related to fatty acid β-oxidation and 7 enzymes of the tricarboxylic acid (TCA) cycle in the db/db mice hearts compared to those with the treatment of NaHS. Exogenous H2S restored the expression of NAMPT and the ratio of NAD+/NADH enhanced the expression and activity of SIRT3. As a result of activation of SIRT3, the acetylation level and activity of fatty acid β-oxidation enzyme LCAD and the acetylation of glucose oxidation enzymes PDH, IDH2, and CS were reduced which resulted in activation of PDH, IDH2, and CS. Our finding suggested that H2S induced a switch in cardiac energy substrate utilization from fatty acid β-oxidation to glucose oxidation in DCM through regulating SIRT3 pathway.H2S regulated the acetylation level and activities of enzymes in fatty acid oxidation and glucose oxidation in cardiac tissues of db/db mice.Exogenous H2S decreased mitochondrial acetylation level through upregulating the expression and activity of SIRT3 in vivo and in vitro.H2S induced a switch in cardiac energy substrate utilization from fatty acid oxidation to glucose.H2S regulated the acetylation level and activities of enzymes in fatty acid oxidation and glucose oxidation in cardiac tissues of db/db mice.Exogenous H2S decreased mitochondrial acetylation level through upregulating the expression and activity of SIRT3 in vivo and in vitro.H2S induced a switch in cardiac energy substrate utilization from fatty acid oxidation to glucose.Hydrogen sulfide (H2S) is involved in diverse physiological functions, such as anti-hypertension, anti-proliferation, regulating ATP synthesis, and reactive oxygen species production. Sirtuin 3 (SIRT3) is a NAD+-dependent deacetylase that regulates mitochondrial energy metabolism. The role of H2S in energy metabolism in diabetic cardiomyopathy (DCM) may be related to regulate SIRT3 expression; however, this role remains to be elucidated. We hypothesized that exogenous H2S could switch cardiac energy metabolic substrate preference by lysine acetylation through promoting the expression of SIRT3 in cardiac tissue of db/db mice. Db/db mice, neonatal rat cardiomyocytes, and H9c2 cell line with the treatment of high glucose, oleate, and palmitate were used as animal and cellular models of type 2 diabetes. Using LC-MS/MS, we identified 76 proteins that increased acetylation, including 8 enzymes related to fatty acid β-oxidation and 7 enzymes of the tricarboxylic acid (TCA) cycle in the db/db mice hearts compared to those with the treatment of NaHS. Exogenous H2S restored the expression of NAMPT and the ratio of NAD+/NADH enhanced the expression and activity of SIRT3. As a result of activation of SIRT3, the acetylation level and activity of fatty acid β-oxidation enzyme LCAD and the acetylation of glucose oxidation enzymes PDH, IDH2, and CS were reduced which resulted in activation of PDH, IDH2, and CS. Our finding suggested that H2S induced a switch in cardiac energy substrate utilization from fatty acid β-oxidation to glucose oxidation in DCM through regulating SIRT3 pathway.H2S regulated the acetylation level and activities of enzymes in fatty acid oxidation and glucose oxidation in cardiac tissues of db/db mice.Exogenous H2S decreased mitochondrial acetylation level through upregulating the expression and activity of SIRT3 in vivo and in vitro.H2S induced a switch in cardiac energy substrate utilization from fatty acid oxidation to glucose.H2S regulated the acetylation level and activities of enzymes in fatty acid oxidation and glucose oxidation in cardiac tissues of db/db mice.Exogenous H2S decreased mitochondrial acetylation level through upregulating the expression and activity of SIRT3 in vivo and in vitro.H2S induced a switch in cardiac energy substrate utilization from fatty acid oxidation to glucose.Hydrogen sulfide (H2S) is involved in diverse physiological functions, such as anti-hypertension, anti-proliferation, regulating ATP synthesis, and reactive oxygen species production. Sirtuin 3 (SIRT3) is a NAD+-dependent deacetylase that regulates mitochondrial energy metabolism. The role of H2S in energy metabolism in diabetic cardiomyopathy (DCM) may be related to regulate SIRT3 expression; however, this role remains to be elucidated. We hypothesized that exogenous H2S could switch cardiac energy metabolic substrate preference by lysine acetylation through promoting the expression of SIRT3 in cardiac tissue of db/db mice. Db/db mice, neonatal rat cardiomyocytes, and H9c2 cell line with the treatment of high glucose, oleate, and palmitate were used as animal and cellular models of type 2 diabetes. Using LC-MS/MS, we identified 76 proteins that increased acetylation, including 8 enzymes related to fatty acid β-oxidation and 7 enzymes of the tricarboxylic acid (TCA) cycle in the db/db mice hearts compared to those with the treatment of NaHS. Exogenous H2S restored the expression of NAMPT and the ratio of NAD+/NADH enhanced the expression and activity of SIRT3. As a result of activation of SIRT3, the acetylation level and activity of fatty acid β-oxidation enzyme LCAD and the acetylation of glucose oxidation enzymes PDH, IDH2, and CS were reduced which resulted in activation of PDH, IDH2, and CS. Our finding suggested that H2S induced a switch in cardiac energy substrate utilization from fatty acid β-oxidation to glucose oxidation in DCM through regulating SIRT3 pathway.H2S regulated the acetylation level and activities of enzymes in fatty acid oxidation and glucose oxidation in cardiac tissues of db/db mice.Exogenous H2S decreased mitochondrial acetylation level through upregulating the expression and activity of SIRT3 in vivo and in vitro.H2S induced a switch in cardiac energy substrate utilization from fatty acid oxidation to glucose.H2S regulated the acetylation level and activities of enzymes in fatty acid oxidation and glucose oxidation in cardiac tissues of db/db mice.Exogenous H2S decreased mitochondrial acetylation level through upregulating the expression and activity of SIRT3 in vivo and in vitro.H2S induced a switch in cardiac energy substrate utilization from fatty acid oxidation to glucose.Hydrogen sulfide (H2S) is involved in diverse physiological functions, such as anti-hypertension, anti-proliferation, regulating ATP synthesis, and reactive oxygen species production. Sirtuin 3 (SIRT3) is a NAD+-dependent deacetylase that regulates mitochondrial energy metabolism. The role of H2S in energy metabolism in diabetic cardiomyopathy (DCM) may be related to regulate SIRT3 expression; however, this role remains to be elucidated. We hypothesized that exogenous H2S could switch cardiac energy metabolic substrate preference by lysine acetylation through promoting the expression of SIRT3 in cardiac tissue of db/db mice. Db/db mice, neonatal rat cardiomyocytes, and H9c2 cell line with the treatment of high glucose, oleate, and palmitate were used as animal and cellular models of type 2 diabetes. Using LC-MS/MS, we identified 76 proteins that increased acetylation, including 8 enzymes related to fatty acid β-oxidation and 7 enzymes of the tricarboxylic acid (TCA) cycle in the db/db mice hearts compared to those with the treatment of NaHS. Exogenous H2S restored the expression of NAMPT and the ratio of NAD+/NADH enhanced the expression and activity of SIRT3. As a result of activation of SIRT3, the acetylation level and activity of fatty acid β-oxidation enzyme LCAD and the acetylation of glucose oxidation enzymes PDH, IDH2, and CS were reduced which resulted in activation of PDH, IDH2, and CS. Our finding suggested that H2S induced a switch in cardiac energy substrate utilization from fatty acid β-oxidation to glucose oxidation in DCM through regulating SIRT3 pathway.H2S regulated the acetylation level and activities of enzymes in fatty acid oxidation and glucose oxidation in cardiac tissues of db/db mice.Exogenous H2S decreased mitochondrial acetylation level through upregulating the expression and activity of SIRT3 in vivo and in vitro.H2S induced a switch in cardiac energy substrate utilization from fatty acid oxidation to glucose.H2S regulated the acetylation level and activities of enzymes in fatty acid oxidation and glucose oxidation in cardiac tissues of db/db mice.Exogenous H2S decreased mitochondrial acetylation level through upregulating the expression and activity of SIRT3 in vivo and in vitro.H2S induced a switch in cardiac energy substrate utilization from fatty acid oxidation to glucose.Hydrogen sulfide (H2S) is involved in diverse physiological functions, such as anti-hypertension, anti-proliferation, regulating ATP synthesis, and reactive oxygen species production. Sirtuin 3 (SIRT3) is a NAD+-dependent deacetylase that regulates mitochondrial energy metabolism. The role of H2S in energy metabolism in diabetic cardiomyopathy (DCM) may be related to regulate SIRT3 expression; however, this role remains to be elucidated. We hypothesized that exogenous H2S could switch cardiac energy metabolic substrate preference by lysine acetylation through promoting the expression of SIRT3 in cardiac tissue of db/db mice. Db/db mice, neonatal rat cardiomyocytes, and H9c2 cell line with the treatment of high glucose, oleate, and palmitate were used as animal and cellular models of type 2 diabetes. Using LC-MS/MS, we identified 76 proteins that increased acetylation, including 8 enzymes related to fatty acid β-oxidation and 7 enzymes of the tricarboxylic acid (TCA) cycle in the db/db mice hearts compared to those with the treatment of NaHS. Exogenous H2S restored the expression of NAMPT and the ratio of NAD+/NADH enhanced the expression and activity of SIRT3. As a result of activation of SIRT3, the acetylation level and activity of fatty acid β-oxidation enzyme LCAD and the acetylation of glucose oxidation enzymes PDH, IDH2, and CS were reduced which resulted in activation of PDH, IDH2, and CS. Our finding suggested that H2S induced a switch in cardiac energy substrate utilization from fatty acid β-oxidation to glucose oxidation in DCM through regulating SIRT3 pathway.H2S regulated the acetylation level and activities of enzymes in fatty acid oxidation and glucose oxidation in cardiac tissues of db/db mice.Exogenous H2S decreased mitochondrial acetylation level through upregulating the expression and activity of SIRT3 in vivo and in vitro.H2S induced a switch in cardiac energy substrate utilization from fatty acid oxidation to glucose.H2S regulated the acetylation level and activities of enzymes in fatty acid oxidation and glucose oxidation in cardiac tissues of db/db mice.Exogenous H2S decreased mitochondrial acetylation level through upregulating the expression and activity of SIRT3 in vivo and in vitro.H2S induced a switch in cardiac energy substrate utilization from fatty acid oxidation to glucose.Hydrogen sulfide (H2S) is involved in diverse physiological functions, such as anti-hypertension, anti-proliferation, regulating ATP synthesis, and reactive oxygen species production. Sirtuin 3 (SIRT3) is a NAD+-dependent deacetylase that regulates mitochondrial energy metabolism. The role of H2S in energy metabolism in diabetic cardiomyopathy (DCM) may be related to regulate SIRT3 expression; however, this role remains to be elucidated. We hypothesized that exogenous H2S could switch cardiac energy metabolic substrate preference by lysine acetylation through promoting the expression of SIRT3 in cardiac tissue of db/db mice. Db/db mice, neonatal rat cardiomyocytes, and H9c2 cell line with the treatment of high glucose, oleate, and palmitate were used as animal and cellular models of type 2 diabetes. Using LC-MS/MS, we identified 76 proteins that increased acetylation, including 8 enzymes related to fatty acid β-oxidation and 7 enzymes of the tricarboxylic acid (TCA) cycle in the db/db mice hearts compared to those with the treatment of NaHS. Exogenous H2S restored the expression of NAMPT and the ratio of NAD+/NADH enhanced the expression and activity of SIRT3. As a result of activation of SIRT3, the acetylation level and activity of fatty acid β-oxidation enzyme LCAD and the acetylation of glucose oxidation enzymes PDH, IDH2, and CS were reduced which resulted in activation of PDH, IDH2, and CS. Our finding suggested that H2S induced a switch in cardiac energy substrate utilization from fatty acid β-oxidation to glucose oxidation in DCM through regulating SIRT3 pathway.H2S regulated the acetylation level and activities of enzymes in fatty acid oxidation and glucose oxidation in cardiac tissues of db/db mice.Exogenous H2S decreased mitochondrial acetylation level through upregulating the expression and activity of SIRT3 in vivo and in vitro.H2S induced a switch in cardiac energy substrate utilization from fatty acid oxidation to glucose.H2S regulated the acetylation level and activities of enzymes in fatty acid oxidation and glucose oxidation in cardiac tissues of db/db mice.Exogenous H2S decreased mitochondrial acetylation level through upregulating the expression and activity of SIRT3 in vivo and in vitro.H2S induced a switch in cardiac energy substrate utilization from fatty acid oxidation to glucose. [ABSTRACT FROM AUTHOR]

Hydrogen sulfide (H 2 S) plays physiological roles in vascular tone regulation, cytoprotection, and ATP synthesis. HMG-CoA reductase degradation protein (Hrd1), an E3 ubiquitin ligase, is involved in protein trafficking. H 2 S may play a role in controlling fatty acid uptake in diabetic cardiomyopathy (DCM) in a manner correlated with modulation of Hrd1 S-sulfhydration; however, this role remains to be elucidated. The aim of the present study was to examine whether H 2 S can attenuate lipid accumulation and to explain the possible mechanisms involved in the regulation of the H 2 S-Hrd1/VAMP3 pathway. Db/db mice and neonatal rat cardiomyocytes treated with high glucose, palmitate and oleate were used as animal and cellular models of type 2 diabetes, respectively. The expression of cystathionine-γ-lyase (CSE), Hrd1, CD36 and VAMP3 was detected by Western blot analysis. In addition, Hrd1 was mutated at Cys115, and Hrd1 S-sulfhydration was examined using an S-sulfhydration assay. VAMP3 ubiquitylation was investigated by immunoprecipitation. Lipid droplet formation was tested by TEM, BODIPY 493/503 staining and oil red O staining. The expression of CSE and Hrd1 was decreased in db/db mice compared to control mice, whereas CD36 and VAMP3 expression was increased. NaHS administration reduced droplet formation, and exogenous H 2 S restored Hrd1 expression, modified S-sulfhydration, and decreased VAMP3 expression in the plasma membrane. Using LC-MS/MS analysis, we identified 85 proteins with decreased ubiquitylation, including 3 vesicle-associated membrane proteins, in the cardiac tissues of model db/db mice compared with NaHS-treated db/db mice. Overexpression of Hrd1 mutated at Cys115 diminished VAMP3 ubiquitylation, whereas it increased CD36 and VAMP3 expression and droplet formation. siRNA-mediated Hrd1 deletion increased the expression of CD36 in the cell membrane. These findings suggested that H 2 S regulates VAMP3 ubiquitylation via Hrd1 S-sulfhydration at Cys115 to prevent CD36 translocation in diabetes., Competing Interests: Disclosure statement The authors have no conflicts of interest to declare., (Copyright: © 2020 Yu et al.)

Hydrogen sulfide (H 2 S), an important gasotransmitter, regulates cardiovascular functions. Mitochondrial damage induced by the overproduction of reactive oxygen species (ROS) results in myocardial injury with a diabetic state. The purpose of this study was to investigate the effects of exogenous H 2 S on mitophagy formation in diabetic cardiomyopathy. In this study, we found that exogenous H 2 S could improve cardiac functions, reduce mitochondrial fragments and ROS levels, enhance mitochondrial respiration chain activities and inhibit mitochondrial apoptosis in the hearts of db/db mice. Our results showed that exogenous H 2 S facilitated parkin translocation into mitochondria and promoted mitophagy formation in the hearts of db/db mice. Our studies further revealed that the ubiquitination level of cytosolic parkin was increased and the expression of USP8, a deubiquitinating enzyme, was decreased in db/db cardiac tissues. S-sulfhydration is a novel posttranslational modification of specific cysteine residues on target proteins by H 2 S. Our results showed that the S-sulfhydration level of USP8 was obviously decreased in vivo and in vitro under hyperglycemia and hyperlipidemia, however, exogenous H 2 S could reverse this effect and promote USP8/parkin interaction. Dithiothreitol, a reducing agent that reverses sulfhydration-mediated covalent modification, increased the ubiquitylation level of parkin, abolished the effects of exogenous H 2 S on USP8 deubiquitylation and suppressed the interaction of USP8 with parkin in neonatal rat cardiomyocytes treated with high glucose, oleate and palmitate. Our findings suggested that H 2 S promoted mitophagy formation by increasing S-sulfhydration of USP8, which enhanced deubiquitination of parkin through the recruitment of parkin in mitochondria., Competing Interests: Conflict of interest The authors declare that they have no competing interests., (Copyright: © 2020 Sun et al.)

Background and Purpose: Hydrogen sulfide (H 2 S) plays important roles as a gasotransmitter in pathologies. Increased expression of the E3 ubiquitin ligase, muscle RING finger-1 (MuRF1), may be involved in diabetic cardiomyopathy. Here we have investigated whether and how exogenous H 2 S alleviates cardiac muscle degradation through modifications of MuRF1 S-sulfhydration in db/db mice., Experimental Approach: Neonatal rat cardiomyocytes were treated with high glucose (40 mM), oleate (100 μM), palmitate (400 μM), and NaHS (100 μM) for 72 hr. MuRF1 was silenced with siRNA technology and mutation at Cys 44 . Endoplasmic reticulum stress markers, MuRF1 expression, and ubiquitination level were measured. db/db mice were injected with NaHS (39 μmol·kg -1 ) for 20 weeks. Echocardiography, cardiac ultrastructure, cystathionine-γ-lyase, cardiac structure proteins expression, and S-sulfhydration production were measured., Key Results: H 2 S levels and cystathionine-γ-lyase protein expression in myocardium were decreased in db/db mice. Exogenous H 2 S reversed endoplasmic reticulum stress, including impairment of the function of cardiomyocytes and structural damage in db/db mice. Exogenous H 2 S could suppress the levels of myosin heavy chain 6 and myosin light chain 2 ubiquitination in cardiac tissues of db/db mice, and MuRF1 was modified by S-sulfhydration, following treatment with exogenous H 2 S, to reduce the interaction between MuRF1 and myosin heavy chain 6 and myosin light chain 2., Conclusions and Implications: Our findings suggest that H 2 S regulates MuRF1 S-sulfhydration at Cys 44 to prevent myocardial degradation in the cardiac tissues of db/db mice., Linked Articles: This article is part of a themed section on Hydrogen Sulfide in Biology & Medicine. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.4/issuetoc., (© 2019 The British Pharmacological Society.)

Hydrogen sulfide (H 2 S), a gaseous molecule, is involved in modulating multiple physiological functions, such as antioxidant, antihypertension, and the production of polysulfide cysteine. H 2 S may inhibit reactive oxygen species generation and ATP production through modulating respiratory chain enzyme activities; however, the mechanism of this effect remains unclear. In this study, db/db mice, neonatal rat cardiomyocytes, and H9c2 cells treated with high glucose, oleate, and palmitate were used as animal and cellular models of type 2 diabetes. The mitochondrial respiratory rate, respiratory chain complex activities, and ATP production were decreased in db/db mice compared with those in db/db mice treated with exogenous H 2 S. Liquid chromatography with tandem mass spectrometry analysis showed that the acetylation level of proteins involved in the mitochondrial respiratory chain were increased in the db/db mice hearts compared with those with sodium hydrosulfide (NaHS) treatment. Exogenous H 2 S restored the ratio of NAD + /NADH, enhanced the expression and activity of sirtuin 3 (SIRT3) and decreased mitochondrial acetylation level in cardiomyocytes under hyperglycemia and hyperlipidemia. As a result of SIRT3 activation, acetylation of the respiratory complexe enzymes NADH dehydrogenase 1 (ND1), ubiquinol cytochrome c reductase core protein 1, and ATP synthase mitochondrial F1 complex assembly factor 1 was reduced, which enhanced the activities of the mitochondrial respiratory chain activity and ATP production. We conclude that exogenous H 2 S plays a critical role in improving cardiac mitochondrial function in diabetes by upregulating SIRT3.

Viral myocarditis is a cardiovascular disease that seriously affects human health. Its mechanism is not clear. Coxsackievirus B3 (CVB3) is a member of the picornavirus family and is the leading cause of viral myocarditis. Our group tested the genes in a mouse model of CVB3 virus infection and confirmed that the NADPH oxidase gene had a high expression trend in the acute phase of infection. Whether Nox4, the homologue of NADPH oxidase, participates in the process of viral myocarditis has not been reported. In this study, we found increased expression of Nox4 in viral myocarditis in vivo and in vitro. DPI is a non-specific inhibitor of Nox4 that improved CVB3-induced myocarditis after injection in vivo. DPI also inhibited intracellular ROS release and apoptosis in vitro. Our data indicated that Nox4-dependent ROS production was involved in CVB3-induced myocardial apoptosis., (Copyright © 2018 Elsevier Inc. All rights reserved.)