Research ArticleEndocrinologyMetabolism Open Access | 10.1172/JCI185340

Yu-Sheng Yeh,1,2 Trent D. Evans,3 Mari Iwase,4 Se-Jin Jeong,3 Xiangyu Zhang,1,2 Ziyang Liu,1,2 Arick Park,3 Ali Ghasemian,3 Borna Dianati,3 Ali Javaheri,3,5 Dagmar Kratky,6 Satoko Kawarasaki,7 Tsuyoshi Goto,7,8 Hanrui Zhang,9 Partha Dutta,1,2 Francisco J. Schopfer,10 Adam C. Straub,10 Jaehyung Cho,11,12 Irfan J. Lodhi,13 and Babak Razani1,2

1Department of Medicine and Vascular Medicine Institute, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center (UPMC), Pittsburgh, Pennsylvania, USA.

2Pittsburgh VA Medical Center, Pittsburgh, Pennsylvania, USA.

3Cardiovascular Division, Washington University School of Medicine, St. Louis, Missouri, USA.

4Division of Oncology, Washington University School of Medicine, St. Louis, Missouri, USA.

5John Cochran VA Medical Center, St. Louis, Missouri, USA.

6Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Division of Molecular Biology and Biochemistry, Medical University of Graz, Graz, Austria.

7Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto, Japan.

8Research Unit for Physiological Chemistry, Center for the Promotion of Interdisciplinary Education and Research, Kyoto University, Kyoto, Japan.

9Department of Medicine, Columbia University Irving Medical Center, New York, New York, USA.

10Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine and UPMC, Pittsburgh, Pennsylvania, USA.

11Division of Hematology, Washington University School of Medicine, St. Louis, Missouri, USA.

12Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.

13Division of Endocrinology, Metabolism, and Lipid Research, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.

Address correspondence to: Babak Razani, University of Pittsburgh School of Medicine and UPMC, BST10 E1043, 200 Lothrop Street, Pittsburgh, Pennsylvania 15261, USA. Phone: 412.648.7496; Email: brazani@pitt.edu.

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1Department of Medicine and Vascular Medicine Institute, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center (UPMC), Pittsburgh, Pennsylvania, USA.

2Pittsburgh VA Medical Center, Pittsburgh, Pennsylvania, USA.

3Cardiovascular Division, Washington University School of Medicine, St. Louis, Missouri, USA.

4Division of Oncology, Washington University School of Medicine, St. Louis, Missouri, USA.

5John Cochran VA Medical Center, St. Louis, Missouri, USA.

6Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Division of Molecular Biology and Biochemistry, Medical University of Graz, Graz, Austria.

7Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto, Japan.

8Research Unit for Physiological Chemistry, Center for the Promotion of Interdisciplinary Education and Research, Kyoto University, Kyoto, Japan.

9Department of Medicine, Columbia University Irving Medical Center, New York, New York, USA.

10Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine and UPMC, Pittsburgh, Pennsylvania, USA.

11Division of Hematology, Washington University School of Medicine, St. Louis, Missouri, USA.

12Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.

13Division of Endocrinology, Metabolism, and Lipid Research, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.

Address correspondence to: Babak Razani, University of Pittsburgh School of Medicine and UPMC, BST10 E1043, 200 Lothrop Street, Pittsburgh, Pennsylvania 15261, USA. Phone: 412.648.7496; Email: brazani@pitt.edu.

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1Department of Medicine and Vascular Medicine Institute, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center (UPMC), Pittsburgh, Pennsylvania, USA.

2Pittsburgh VA Medical Center, Pittsburgh, Pennsylvania, USA.

3Cardiovascular Division, Washington University School of Medicine, St. Louis, Missouri, USA.

4Division of Oncology, Washington University School of Medicine, St. Louis, Missouri, USA.

5John Cochran VA Medical Center, St. Louis, Missouri, USA.

6Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Division of Molecular Biology and Biochemistry, Medical University of Graz, Graz, Austria.

7Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto, Japan.

8Research Unit for Physiological Chemistry, Center for the Promotion of Interdisciplinary Education and Research, Kyoto University, Kyoto, Japan.

9Department of Medicine, Columbia University Irving Medical Center, New York, New York, USA.

10Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine and UPMC, Pittsburgh, Pennsylvania, USA.

11Division of Hematology, Washington University School of Medicine, St. Louis, Missouri, USA.

12Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.

13Division of Endocrinology, Metabolism, and Lipid Research, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.

Address correspondence to: Babak Razani, University of Pittsburgh School of Medicine and UPMC, BST10 E1043, 200 Lothrop Street, Pittsburgh, Pennsylvania 15261, USA. Phone: 412.648.7496; Email: brazani@pitt.edu.

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1Department of Medicine and Vascular Medicine Institute, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center (UPMC), Pittsburgh, Pennsylvania, USA.

2Pittsburgh VA Medical Center, Pittsburgh, Pennsylvania, USA.

3Cardiovascular Division, Washington University School of Medicine, St. Louis, Missouri, USA.

4Division of Oncology, Washington University School of Medicine, St. Louis, Missouri, USA.

5John Cochran VA Medical Center, St. Louis, Missouri, USA.

6Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Division of Molecular Biology and Biochemistry, Medical University of Graz, Graz, Austria.

7Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto, Japan.

8Research Unit for Physiological Chemistry, Center for the Promotion of Interdisciplinary Education and Research, Kyoto University, Kyoto, Japan.

9Department of Medicine, Columbia University Irving Medical Center, New York, New York, USA.

10Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine and UPMC, Pittsburgh, Pennsylvania, USA.

11Division of Hematology, Washington University School of Medicine, St. Louis, Missouri, USA.

12Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.

13Division of Endocrinology, Metabolism, and Lipid Research, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.

Address correspondence to: Babak Razani, University of Pittsburgh School of Medicine and UPMC, BST10 E1043, 200 Lothrop Street, Pittsburgh, Pennsylvania 15261, USA. Phone: 412.648.7496; Email: brazani@pitt.edu.

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1Department of Medicine and Vascular Medicine Institute, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center (UPMC), Pittsburgh, Pennsylvania, USA.

2Pittsburgh VA Medical Center, Pittsburgh, Pennsylvania, USA.

3Cardiovascular Division, Washington University School of Medicine, St. Louis, Missouri, USA.

4Division of Oncology, Washington University School of Medicine, St. Louis, Missouri, USA.

5John Cochran VA Medical Center, St. Louis, Missouri, USA.

6Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Division of Molecular Biology and Biochemistry, Medical University of Graz, Graz, Austria.

7Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto, Japan.

8Research Unit for Physiological Chemistry, Center for the Promotion of Interdisciplinary Education and Research, Kyoto University, Kyoto, Japan.

9Department of Medicine, Columbia University Irving Medical Center, New York, New York, USA.

10Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine and UPMC, Pittsburgh, Pennsylvania, USA.

11Division of Hematology, Washington University School of Medicine, St. Louis, Missouri, USA.

12Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.

13Division of Endocrinology, Metabolism, and Lipid Research, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.

Address correspondence to: Babak Razani, University of Pittsburgh School of Medicine and UPMC, BST10 E1043, 200 Lothrop Street, Pittsburgh, Pennsylvania 15261, USA. Phone: 412.648.7496; Email: brazani@pitt.edu.

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1Department of Medicine and Vascular Medicine Institute, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center (UPMC), Pittsburgh, Pennsylvania, USA.

2Pittsburgh VA Medical Center, Pittsburgh, Pennsylvania, USA.

3Cardiovascular Division, Washington University School of Medicine, St. Louis, Missouri, USA.

4Division of Oncology, Washington University School of Medicine, St. Louis, Missouri, USA.

5John Cochran VA Medical Center, St. Louis, Missouri, USA.

6Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Division of Molecular Biology and Biochemistry, Medical University of Graz, Graz, Austria.

7Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto, Japan.

8Research Unit for Physiological Chemistry, Center for the Promotion of Interdisciplinary Education and Research, Kyoto University, Kyoto, Japan.

9Department of Medicine, Columbia University Irving Medical Center, New York, New York, USA.

10Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine and UPMC, Pittsburgh, Pennsylvania, USA.

11Division of Hematology, Washington University School of Medicine, St. Louis, Missouri, USA.

12Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.

13Division of Endocrinology, Metabolism, and Lipid Research, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.

Address correspondence to: Babak Razani, University of Pittsburgh School of Medicine and UPMC, BST10 E1043, 200 Lothrop Street, Pittsburgh, Pennsylvania 15261, USA. Phone: 412.648.7496; Email: brazani@pitt.edu.

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1Department of Medicine and Vascular Medicine Institute, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center (UPMC), Pittsburgh, Pennsylvania, USA.

2Pittsburgh VA Medical Center, Pittsburgh, Pennsylvania, USA.

3Cardiovascular Division, Washington University School of Medicine, St. Louis, Missouri, USA.

4Division of Oncology, Washington University School of Medicine, St. Louis, Missouri, USA.

5John Cochran VA Medical Center, St. Louis, Missouri, USA.

6Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Division of Molecular Biology and Biochemistry, Medical University of Graz, Graz, Austria.

7Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto, Japan.

8Research Unit for Physiological Chemistry, Center for the Promotion of Interdisciplinary Education and Research, Kyoto University, Kyoto, Japan.

9Department of Medicine, Columbia University Irving Medical Center, New York, New York, USA.

10Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine and UPMC, Pittsburgh, Pennsylvania, USA.

11Division of Hematology, Washington University School of Medicine, St. Louis, Missouri, USA.

12Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.

13Division of Endocrinology, Metabolism, and Lipid Research, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.

Address correspondence to: Babak Razani, University of Pittsburgh School of Medicine and UPMC, BST10 E1043, 200 Lothrop Street, Pittsburgh, Pennsylvania 15261, USA. Phone: 412.648.7496; Email: brazani@pitt.edu.

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1Department of Medicine and Vascular Medicine Institute, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center (UPMC), Pittsburgh, Pennsylvania, USA.

2Pittsburgh VA Medical Center, Pittsburgh, Pennsylvania, USA.

3Cardiovascular Division, Washington University School of Medicine, St. Louis, Missouri, USA.

4Division of Oncology, Washington University School of Medicine, St. Louis, Missouri, USA.

5John Cochran VA Medical Center, St. Louis, Missouri, USA.

6Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Division of Molecular Biology and Biochemistry, Medical University of Graz, Graz, Austria.

7Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto, Japan.

8Research Unit for Physiological Chemistry, Center for the Promotion of Interdisciplinary Education and Research, Kyoto University, Kyoto, Japan.

9Department of Medicine, Columbia University Irving Medical Center, New York, New York, USA.

10Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine and UPMC, Pittsburgh, Pennsylvania, USA.

11Division of Hematology, Washington University School of Medicine, St. Louis, Missouri, USA.

12Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.

13Division of Endocrinology, Metabolism, and Lipid Research, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.

Address correspondence to: Babak Razani, University of Pittsburgh School of Medicine and UPMC, BST10 E1043, 200 Lothrop Street, Pittsburgh, Pennsylvania 15261, USA. Phone: 412.648.7496; Email: brazani@pitt.edu.

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1Department of Medicine and Vascular Medicine Institute, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center (UPMC), Pittsburgh, Pennsylvania, USA.

2Pittsburgh VA Medical Center, Pittsburgh, Pennsylvania, USA.

3Cardiovascular Division, Washington University School of Medicine, St. Louis, Missouri, USA.

4Division of Oncology, Washington University School of Medicine, St. Louis, Missouri, USA.

5John Cochran VA Medical Center, St. Louis, Missouri, USA.

6Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Division of Molecular Biology and Biochemistry, Medical University of Graz, Graz, Austria.

7Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto, Japan.

8Research Unit for Physiological Chemistry, Center for the Promotion of Interdisciplinary Education and Research, Kyoto University, Kyoto, Japan.

9Department of Medicine, Columbia University Irving Medical Center, New York, New York, USA.

10Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine and UPMC, Pittsburgh, Pennsylvania, USA.

11Division of Hematology, Washington University School of Medicine, St. Louis, Missouri, USA.

12Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.

13Division of Endocrinology, Metabolism, and Lipid Research, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.

Address correspondence to: Babak Razani, University of Pittsburgh School of Medicine and UPMC, BST10 E1043, 200 Lothrop Street, Pittsburgh, Pennsylvania 15261, USA. Phone: 412.648.7496; Email: brazani@pitt.edu.

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1Department of Medicine and Vascular Medicine Institute, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center (UPMC), Pittsburgh, Pennsylvania, USA.

2Pittsburgh VA Medical Center, Pittsburgh, Pennsylvania, USA.

3Cardiovascular Division, Washington University School of Medicine, St. Louis, Missouri, USA.

4Division of Oncology, Washington University School of Medicine, St. Louis, Missouri, USA.

5John Cochran VA Medical Center, St. Louis, Missouri, USA.

6Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Division of Molecular Biology and Biochemistry, Medical University of Graz, Graz, Austria.

7Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto, Japan.

8Research Unit for Physiological Chemistry, Center for the Promotion of Interdisciplinary Education and Research, Kyoto University, Kyoto, Japan.

9Department of Medicine, Columbia University Irving Medical Center, New York, New York, USA.

10Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine and UPMC, Pittsburgh, Pennsylvania, USA.

11Division of Hematology, Washington University School of Medicine, St. Louis, Missouri, USA.

12Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.

13Division of Endocrinology, Metabolism, and Lipid Research, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.

Address correspondence to: Babak Razani, University of Pittsburgh School of Medicine and UPMC, BST10 E1043, 200 Lothrop Street, Pittsburgh, Pennsylvania 15261, USA. Phone: 412.648.7496; Email: brazani@pitt.edu.

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1Department of Medicine and Vascular Medicine Institute, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center (UPMC), Pittsburgh, Pennsylvania, USA.

2Pittsburgh VA Medical Center, Pittsburgh, Pennsylvania, USA.

3Cardiovascular Division, Washington University School of Medicine, St. Louis, Missouri, USA.

4Division of Oncology, Washington University School of Medicine, St. Louis, Missouri, USA.

5John Cochran VA Medical Center, St. Louis, Missouri, USA.

6Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Division of Molecular Biology and Biochemistry, Medical University of Graz, Graz, Austria.

7Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto, Japan.

8Research Unit for Physiological Chemistry, Center for the Promotion of Interdisciplinary Education and Research, Kyoto University, Kyoto, Japan.

9Department of Medicine, Columbia University Irving Medical Center, New York, New York, USA.

10Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine and UPMC, Pittsburgh, Pennsylvania, USA.

11Division of Hematology, Washington University School of Medicine, St. Louis, Missouri, USA.

12Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.

13Division of Endocrinology, Metabolism, and Lipid Research, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.

Address correspondence to: Babak Razani, University of Pittsburgh School of Medicine and UPMC, BST10 E1043, 200 Lothrop Street, Pittsburgh, Pennsylvania 15261, USA. Phone: 412.648.7496; Email: brazani@pitt.edu.

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1Department of Medicine and Vascular Medicine Institute, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center (UPMC), Pittsburgh, Pennsylvania, USA.

2Pittsburgh VA Medical Center, Pittsburgh, Pennsylvania, USA.

3Cardiovascular Division, Washington University School of Medicine, St. Louis, Missouri, USA.

4Division of Oncology, Washington University School of Medicine, St. Louis, Missouri, USA.

5John Cochran VA Medical Center, St. Louis, Missouri, USA.

6Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Division of Molecular Biology and Biochemistry, Medical University of Graz, Graz, Austria.

7Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto, Japan.

8Research Unit for Physiological Chemistry, Center for the Promotion of Interdisciplinary Education and Research, Kyoto University, Kyoto, Japan.

9Department of Medicine, Columbia University Irving Medical Center, New York, New York, USA.

10Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine and UPMC, Pittsburgh, Pennsylvania, USA.

11Division of Hematology, Washington University School of Medicine, St. Louis, Missouri, USA.

12Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.

13Division of Endocrinology, Metabolism, and Lipid Research, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.

Address correspondence to: Babak Razani, University of Pittsburgh School of Medicine and UPMC, BST10 E1043, 200 Lothrop Street, Pittsburgh, Pennsylvania 15261, USA. Phone: 412.648.7496; Email: brazani@pitt.edu.

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1Department of Medicine and Vascular Medicine Institute, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center (UPMC), Pittsburgh, Pennsylvania, USA.

2Pittsburgh VA Medical Center, Pittsburgh, Pennsylvania, USA.

3Cardiovascular Division, Washington University School of Medicine, St. Louis, Missouri, USA.

4Division of Oncology, Washington University School of Medicine, St. Louis, Missouri, USA.

5John Cochran VA Medical Center, St. Louis, Missouri, USA.

6Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Division of Molecular Biology and Biochemistry, Medical University of Graz, Graz, Austria.

7Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto, Japan.

8Research Unit for Physiological Chemistry, Center for the Promotion of Interdisciplinary Education and Research, Kyoto University, Kyoto, Japan.

9Department of Medicine, Columbia University Irving Medical Center, New York, New York, USA.

10Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine and UPMC, Pittsburgh, Pennsylvania, USA.

11Division of Hematology, Washington University School of Medicine, St. Louis, Missouri, USA.

12Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.

13Division of Endocrinology, Metabolism, and Lipid Research, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.

Address correspondence to: Babak Razani, University of Pittsburgh School of Medicine and UPMC, BST10 E1043, 200 Lothrop Street, Pittsburgh, Pennsylvania 15261, USA. Phone: 412.648.7496; Email: brazani@pitt.edu.

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1Department of Medicine and Vascular Medicine Institute, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center (UPMC), Pittsburgh, Pennsylvania, USA.

2Pittsburgh VA Medical Center, Pittsburgh, Pennsylvania, USA.

3Cardiovascular Division, Washington University School of Medicine, St. Louis, Missouri, USA.

4Division of Oncology, Washington University School of Medicine, St. Louis, Missouri, USA.

5John Cochran VA Medical Center, St. Louis, Missouri, USA.

6Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Division of Molecular Biology and Biochemistry, Medical University of Graz, Graz, Austria.

7Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto, Japan.

8Research Unit for Physiological Chemistry, Center for the Promotion of Interdisciplinary Education and Research, Kyoto University, Kyoto, Japan.

9Department of Medicine, Columbia University Irving Medical Center, New York, New York, USA.

10Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine and UPMC, Pittsburgh, Pennsylvania, USA.

11Division of Hematology, Washington University School of Medicine, St. Louis, Missouri, USA.

12Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.

13Division of Endocrinology, Metabolism, and Lipid Research, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.

Address correspondence to: Babak Razani, University of Pittsburgh School of Medicine and UPMC, BST10 E1043, 200 Lothrop Street, Pittsburgh, Pennsylvania 15261, USA. Phone: 412.648.7496; Email: brazani@pitt.edu.

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1Department of Medicine and Vascular Medicine Institute, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center (UPMC), Pittsburgh, Pennsylvania, USA.

2Pittsburgh VA Medical Center, Pittsburgh, Pennsylvania, USA.

3Cardiovascular Division, Washington University School of Medicine, St. Louis, Missouri, USA.

4Division of Oncology, Washington University School of Medicine, St. Louis, Missouri, USA.

5John Cochran VA Medical Center, St. Louis, Missouri, USA.

6Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Division of Molecular Biology and Biochemistry, Medical University of Graz, Graz, Austria.

7Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto, Japan.

8Research Unit for Physiological Chemistry, Center for the Promotion of Interdisciplinary Education and Research, Kyoto University, Kyoto, Japan.

9Department of Medicine, Columbia University Irving Medical Center, New York, New York, USA.

10Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine and UPMC, Pittsburgh, Pennsylvania, USA.

11Division of Hematology, Washington University School of Medicine, St. Louis, Missouri, USA.

12Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.

13Division of Endocrinology, Metabolism, and Lipid Research, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.

Address correspondence to: Babak Razani, University of Pittsburgh School of Medicine and UPMC, BST10 E1043, 200 Lothrop Street, Pittsburgh, Pennsylvania 15261, USA. Phone: 412.648.7496; Email: brazani@pitt.edu.

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1Department of Medicine and Vascular Medicine Institute, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center (UPMC), Pittsburgh, Pennsylvania, USA.

2Pittsburgh VA Medical Center, Pittsburgh, Pennsylvania, USA.

3Cardiovascular Division, Washington University School of Medicine, St. Louis, Missouri, USA.

4Division of Oncology, Washington University School of Medicine, St. Louis, Missouri, USA.

5John Cochran VA Medical Center, St. Louis, Missouri, USA.

6Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Division of Molecular Biology and Biochemistry, Medical University of Graz, Graz, Austria.

7Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto, Japan.

8Research Unit for Physiological Chemistry, Center for the Promotion of Interdisciplinary Education and Research, Kyoto University, Kyoto, Japan.

9Department of Medicine, Columbia University Irving Medical Center, New York, New York, USA.

10Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine and UPMC, Pittsburgh, Pennsylvania, USA.

11Division of Hematology, Washington University School of Medicine, St. Louis, Missouri, USA.

12Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.

13Division of Endocrinology, Metabolism, and Lipid Research, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.

Address correspondence to: Babak Razani, University of Pittsburgh School of Medicine and UPMC, BST10 E1043, 200 Lothrop Street, Pittsburgh, Pennsylvania 15261, USA. Phone: 412.648.7496; Email: brazani@pitt.edu.

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1Department of Medicine and Vascular Medicine Institute, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center (UPMC), Pittsburgh, Pennsylvania, USA.

2Pittsburgh VA Medical Center, Pittsburgh, Pennsylvania, USA.

3Cardiovascular Division, Washington University School of Medicine, St. Louis, Missouri, USA.

4Division of Oncology, Washington University School of Medicine, St. Louis, Missouri, USA.

5John Cochran VA Medical Center, St. Louis, Missouri, USA.

6Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Division of Molecular Biology and Biochemistry, Medical University of Graz, Graz, Austria.

7Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto, Japan.

8Research Unit for Physiological Chemistry, Center for the Promotion of Interdisciplinary Education and Research, Kyoto University, Kyoto, Japan.

9Department of Medicine, Columbia University Irving Medical Center, New York, New York, USA.

10Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine and UPMC, Pittsburgh, Pennsylvania, USA.

11Division of Hematology, Washington University School of Medicine, St. Louis, Missouri, USA.

12Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.

13Division of Endocrinology, Metabolism, and Lipid Research, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.

Address correspondence to: Babak Razani, University of Pittsburgh School of Medicine and UPMC, BST10 E1043, 200 Lothrop Street, Pittsburgh, Pennsylvania 15261, USA. Phone: 412.648.7496; Email: brazani@pitt.edu.

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1Department of Medicine and Vascular Medicine Institute, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center (UPMC), Pittsburgh, Pennsylvania, USA.

2Pittsburgh VA Medical Center, Pittsburgh, Pennsylvania, USA.

3Cardiovascular Division, Washington University School of Medicine, St. Louis, Missouri, USA.

4Division of Oncology, Washington University School of Medicine, St. Louis, Missouri, USA.

5John Cochran VA Medical Center, St. Louis, Missouri, USA.

6Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Division of Molecular Biology and Biochemistry, Medical University of Graz, Graz, Austria.

7Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto, Japan.

8Research Unit for Physiological Chemistry, Center for the Promotion of Interdisciplinary Education and Research, Kyoto University, Kyoto, Japan.

9Department of Medicine, Columbia University Irving Medical Center, New York, New York, USA.

10Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine and UPMC, Pittsburgh, Pennsylvania, USA.

11Division of Hematology, Washington University School of Medicine, St. Louis, Missouri, USA.

12Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.

13Division of Endocrinology, Metabolism, and Lipid Research, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.

Address correspondence to: Babak Razani, University of Pittsburgh School of Medicine and UPMC, BST10 E1043, 200 Lothrop Street, Pittsburgh, Pennsylvania 15261, USA. Phone: 412.648.7496; Email: brazani@pitt.edu.

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1Department of Medicine and Vascular Medicine Institute, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center (UPMC), Pittsburgh, Pennsylvania, USA.

2Pittsburgh VA Medical Center, Pittsburgh, Pennsylvania, USA.

3Cardiovascular Division, Washington University School of Medicine, St. Louis, Missouri, USA.

4Division of Oncology, Washington University School of Medicine, St. Louis, Missouri, USA.

5John Cochran VA Medical Center, St. Louis, Missouri, USA.

6Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Division of Molecular Biology and Biochemistry, Medical University of Graz, Graz, Austria.

7Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto, Japan.

8Research Unit for Physiological Chemistry, Center for the Promotion of Interdisciplinary Education and Research, Kyoto University, Kyoto, Japan.

9Department of Medicine, Columbia University Irving Medical Center, New York, New York, USA.

10Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine and UPMC, Pittsburgh, Pennsylvania, USA.

11Division of Hematology, Washington University School of Medicine, St. Louis, Missouri, USA.

12Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.

13Division of Endocrinology, Metabolism, and Lipid Research, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.

Address correspondence to: Babak Razani, University of Pittsburgh School of Medicine and UPMC, BST10 E1043, 200 Lothrop Street, Pittsburgh, Pennsylvania 15261, USA. Phone: 412.648.7496; Email: brazani@pitt.edu.

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1Department of Medicine and Vascular Medicine Institute, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center (UPMC), Pittsburgh, Pennsylvania, USA.

2Pittsburgh VA Medical Center, Pittsburgh, Pennsylvania, USA.

3Cardiovascular Division, Washington University School of Medicine, St. Louis, Missouri, USA.

4Division of Oncology, Washington University School of Medicine, St. Louis, Missouri, USA.

5John Cochran VA Medical Center, St. Louis, Missouri, USA.

6Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Division of Molecular Biology and Biochemistry, Medical University of Graz, Graz, Austria.

7Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto, Japan.

8Research Unit for Physiological Chemistry, Center for the Promotion of Interdisciplinary Education and Research, Kyoto University, Kyoto, Japan.

9Department of Medicine, Columbia University Irving Medical Center, New York, New York, USA.

10Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine and UPMC, Pittsburgh, Pennsylvania, USA.

11Division of Hematology, Washington University School of Medicine, St. Louis, Missouri, USA.

12Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.

13Division of Endocrinology, Metabolism, and Lipid Research, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.

Address correspondence to: Babak Razani, University of Pittsburgh School of Medicine and UPMC, BST10 E1043, 200 Lothrop Street, Pittsburgh, Pennsylvania 15261, USA. Phone: 412.648.7496; Email: brazani@pitt.edu.

Find articles by Razani, B. in: JCI | PubMed | Google Scholar |

Published March 17, 2025 - More info

Published in Volume 135, Issue 6 on March 17, 2025
J Clin Invest. 2025;135(6):e185340. https://doi.org/10.1172/JCI185340.
© 2025 Yeh et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. Published March 17, 2025 - Version history
Received: July 26, 2024; Accepted: January 16, 2025 View PDF Abstract

Adipose tissue lipolysis is the process by which triglycerides in lipid stores are hydrolyzed into free fatty acids (FFAs), serving as fuel during fasting or cold-induced thermogenesis. Although cytosolic lipases are considered the predominant mechanism of liberating FFAs, lipolysis also occurs in lysosomes via lysosomal acid lipase (LIPA), albeit with unclear roles in lipid storage and whole-body metabolism. We found that adipocyte LIPA expression increased in adipose tissue of mice when lipolysis was stimulated during fasting, cold exposure, or β-adrenergic agonism. This was functionally important, as inhibition of LIPA genetically or pharmacologically resulted in lower plasma FFAs under lipolytic conditions. Furthermore, adipocyte LIPA deficiency impaired thermogenesis and oxygen consumption and rendered mice susceptible to diet-induced obesity. Importantly, lysosomal lipolysis was independent of adipose triglyceride lipase, the rate-limiting enzyme of cytosolic lipolysis. Our data suggest a significant role for LIPA and lysosomal lipolysis in adipocyte lipid metabolism beyond classical cytosolic lipolysis.

Graphical Abstract Introduction