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BACKGROUND: At present, there is no consensus and guideline for balanced hemostasis and anticoagulation in elderly patients with intertrochanteric fractures. There are few related literatures on the perioperative hemostasis and anticoagulation management of tranexamic acid combined with rivaroxaban in elderly patients with intertrochanteric fractures. OBJECTIVE: To investigate the effects of tranexamic acid combined with rivaroxaban on perioperative hemorrhage, blood transfusion, postoperative venous thrombosis in elderly patients with intertrochanteric fractures. METHODS: Sixty elderly patients with intertrochanteric fractures were enrolled and scheduled to undergo proximal femoral nail anti-rotation surgery. All patients received rivaroxaban 10 mg/d anticoagulant until 24 hours before operation. All patients were divided into two groups. Patients in the test group were intravenously injected with 1.0 g of tranexamic acid. Patients in the control group were intravenously injected with the same volume of glucose solution. Surgical blood loss, blood transfusion, and venous thrombosis prior to discharge were compared in the two groups. RESULTS AND CONCLUSION: (1) The blood loss in the test group was significantly lower than that in the control group (P < 0.05). There was no significant difference in venous thrombosis before discharge between the two groups. (2) Three patients in the test group received blood transfusions, and seven patients in the control group received blood transfusions. (3) The results confirm that tranexamic acid combined with rivaroxaban not only reduces perioperative blood loss in elderly patients with intertrochanteric fractures, but also does not increase the risk of venous thrombosis. [ABSTRACT FROM AUTHOR]

Background/Aim: Autophagy plays an important role in cellular homeostasis through the disposal and recycling of cellular components. Hydrogen sulphide (H2S) is the third endogenous gas that has been shown to confer cardiac protective effects. Given the regulation of autophagy in cardioprotection, this study aimed to investigate the protective effects of H2S via autophagy during high glucose treatment. Methods: This study investigated the content of H2S in the plasma as well as myocardial, ultrastructural changes in mitochondria and autophagosomes. This study also investigated the apoptotic rate using Hoechst/PI as well as expression of autophagy-associated proteins and mitochondrial apoptotic proteins in H9C2 cells treated with or without GYY4137. Mitochondria of cardiac tissues were isolated and RCR and ADP/O were also detected. AMPK knockdown was performed with siRNA transfection. Results: In a STZ-induced diabetic model, NaHS treatment not only increased the expression of p-AMPK in diabetic group but further activated cell autophagy. Following 48h high glucose, autophagosomes and cell viability were reduced. The present results showed that autophagy could be induced by H2S, which was verified by autophagic ultrastructural observation and LC3-I/LC3-II conversion. In addition, the mitochondrial membrane potential (MMP) was significantly decreased. The expressions levels of autophagic-related proteins were significantly elevated. Moreover, H2S activated the AMPK/rapamycin (mTOR) signalling pathway. Conclusions: Our findings demonstrated that H2S decreases oxidative stress and protects against mitochondria injury, activates autophagy, and eventually leads to cardiac protection via the AMPK/mTOR pathway. [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]

Diabetic cardiomyopathy (DCM) is a serious complication of diabetes. Hydrogen sulphide (H 2 S), a newly found gaseous signalling molecule, has an important role in many regulatory functions. The purpose of this study is to investigate the effects of exogenous H 2 S on autophagy and its possible mechanism in DCM induced by type II diabetes (T2DCM). In this study, we found that sodium hydrosulphide (NaHS) attenuated the augment in left ventricular (LV) mass and increased LV volume, decreased reactive oxygen species (ROS) production and ameliorated H 2 S production in the hearts of db/db mice. NaHS facilitated autophagosome content degradation, reduced the expression of P62 (a known substrate of autophagy) and increased the expression of microtubule-associated protein 1 light chain 3 II. It also increased the expression of autophagy-related protein 7 (ATG7) and Beclin1 in db/db mouse hearts. NaHS increased the expression of Kelch-like ECH-associated protein 1 (Keap-1) and reduced the ubiquitylation level in the hearts of db/db mice. 1,4-Dithiothreitol, an inhibitor of disulphide bonds, increased the ubiquitylation level of Keap-1, suppressed the expression of Keap-1 and abolished the effects of NaHS on ubiquitin aggregate clearance and ROS production in H9C2 cells treated with high glucose and palmitate. Overall, we concluded that exogenous H 2 S promoted ubiquitin aggregate clearance via autophagy, which might exert its antioxidative effect in db/db mouse myocardia. Moreover, exogenous H 2 S increased Keap-1 expression by suppressing its ubiquitylation, which might have an important role in ubiquitin aggregate clearance via autophagy. Our findings provide new insight into the mechanisms responsible for the antioxidative effects of H 2 S in the context of T2DCM.