Salman Azhar

Salman Azhar, PhD, Associate Director for Research, GRECC, VA Palo Alto Health Care System; Adjunct Professor, Department of Medicine, Division of Endocrinology, Stanford University School of Medicine 

Research Description: Dr. Azhar’s group investigates small molecules as potential drugs to treat metabolic syndrome (MetS), nonalcoholic fatty liver disease (NAFLD, which is a cause and consequence of MetS) and associated diabetes complications. For example, he has shown that nordihydroguaiaretic acid (NDGA) has a profound ameliorative effect on the core components of MetS, including lowering triglyceride levels and attenuating elevated blood pressure in rodent models, leading to improved obesity, insulin resistance, diabetes, and NAFLD pathology. Dr. Azhar’s recent work suggests that NDGA exerts its hypolipidemic actions primarily by stimulating the activity of PPARalpha, the master regulator of hepatic fatty acid oxidation systems, which, in turn, improves dyslipidemia by promoting increased channeling of fatty acids towards their oxidation and thereby restricting production, storage and secretion of VLDL-TG. Further studies demonstrated that NDGA ameliorates nonalcoholic steatohepatitis (NASH) pathology in a novel mouse model. Additional studies are underway to further explore the underlying mechanisms by which NDGA and its potent analog (agonist), NDGA-A4 exert their beneficial action particularly on dyslipidemia and insulin resistance, the core components of MetS and NAFLD.

Selected relevant publications (Stanford DRC members in BOLD):

  1. Han L, Bittner S, Dong D, Cortez Y, Bittner A, Chan J, Umar M, Shen WJ, Peterson RG, Kraemer FB, Azhar S. Molecular changes in hepatic metabolism in ZDSD rats-A new polygenic rodent model of obesity, metabolic syndrome, and diabetes. Biochim Biophys Acta Mol Basis Dis. 2020 May 1;1866(5):165688. doi: 10.1016/j.bbadis.2020.165688. PMID: 31987840. 

  2. Azhar S, Dong D, Shen WJ, Hu Z, Kraemer FB. The role of miRNAs in regulating adrenal and gonadal steroidogenesis. J Mol Endocrinol. 2020 Jan;64(1):R21-R43. doi: 10.1530/JME-19-0105. PMID: 31671401; PMCID: PMC7202133. 

  3. Wang W, Yan Z, Hu J, Shen WJ, Azhar S, Kraemer FB. Scavenger receptor class B, type 1 facilitates cellular fatty acid uptake. Biochim Biophys Acta Mol Cell Biol Lipids. 2020 Feb;1865(2):158554. doi: 10.1016/j.bbalip.2019.158554. PMID: 31678516; PMCID: PMC6957692. 

  4. Hasbargen KB, Shen WJ, Zhang Y, Hou X, Wang W, Shuo Q, Bernlohr DA, Azhar S, Kraemer FB. Slc43a3 is a regulator of free fatty acid flux. J Lipid Res. 2020 May;61(5):734-745. doi: 10.1194/jlr.RA119000294. PMID: 32217606; PMCID: PMC7193958. 

  5. Wang W, Hao X, Han L, Yan Z, Shen WJ, Dong D, Hasbargen K, Bittner S, Cortez Y, Greenberg AS, Azhar S, Kraemer FB. Tissue-Specific Ablation of ACSL4 Results in Disturbed Steroidogenesis. Endocrinology. 2019 Nov 1;160(11):2517-2528. doi: 10.1210/en.2019-00464. PMID: 31504388; PMCID: PMC6773434. 

  6. Han L, Bittner S, Dong D, Cortez Y, Dulay H, Arshad S, Shen WJ, Kraemer FB, Azhar S. Creosote bush-derived NDGA attenuates molecular and pathological changes in a novel mouse model of nonalcoholic steatohepatitis (NASH). Mol Cell Endocrinol. 2019 Dec 1;498:110538. doi: 10.1016/j.mce.2019.110538. PMID:31415794; PMCID: PMC7273809.   

  7. Singh M, Bittner S, Li Y, Bittner A, Huan L, Cortez Y, Inayathullah M, Arif Z, Parthasarthi R, Rajadas J, Shen W-J, Nicolls MR, Kraemer FB, Azhar S. Anti-hyperlipidemic effects of synthetic analogues of nondihydroguaiaretic acid in dyslipidemic rats. Br J Pharmacol. 2019 Feb;176(3):369-385. doi: 10.1111/bph.14528. PMID: 30374952; PMCID: PMC6329620.  

  8. Azhar S, Bittner S, Hu J, Shen W-J, Cortez Y, Hao X, Han L, Lagerstedt JO, Kraemer FB, Johansson JO. Novel ABCA1 peptide agonists with antidiabetic action. Mol Cell Endocrinol. 2019 Jan 15;480:1-11. doi: 10.1016/j.mce.2018.09.011. PMID: 30290217; PMCID: PMC6626528.

  9. Shen WJ, Huang TT, Cortez Y, Zaidi SK, Arshad S, Kraemer FB, Azhar S. Ablation of Steroidogenic Superoxide Dismutase 2 Increases Oxidative Stress and Diminishes Steroid Hormone Production. Endocrinology. 2025 Jul 8;166(9):bqaf120. doi: 10.1210/endocr/bqaf120. PMID: 40658720; PMCID: PMC12343108. 

  10. Shen WJ, Still Ii C, Han L, Yang P, Chen J, Wosczyna M, Salmon BJR, Perez KC, Li J, Cuevas PL, Liu B, Azhar S, Helms J, Qi LS, Kraemer FB. Hormone sensitive lipase ablation promotes bone regeneration. Biochim Biophys Acta Mol Basis Dis. 2022 Sep 1;1868(9):166449. doi: 10.1016/j.bbadis.2022.166449. Epub 2022 May 23. Erratum in: Biochim Biophys Acta Mol Basis Dis. 2022 Nov 1;1868(11):166506. doi: 10.1016/j.bbadis.2022.166506. PMID: 35618183. 

  11. Hao X, Zhu B, Yang P, Dong D, Sahbaie P, Oliver PL, Shen WJ, Azhar S, Kraemer FB. SNAP25 mutation disrupts metabolic homeostasis, steroid hormone production and central neurobehavior. Biochim Biophys Acta Mol Basis Dis. 2022 Feb 1;1868(2):166304. doi: 10.1016/j.bbadis.2021.166304. Epub 2021 Nov 24. PMID: 34826585; PMCID: PMC8759409. 

  12. Shen WJ, Cortez Y, Singh A, Chen W, Azhar S, Kraemer FB. Mice deficient in ER protein seipin have reduced adrenal cholesteryl ester lipid droplet formation and utilization. J Lipid Res. 2022 Dec;63(12):100309. doi: 10.1016/j.jlr.2022.100309. Epub 2022 Nov 1. PMID: 36332685; PMCID: PMC9703635. 

  13. Zaidi SK, Shen WJ, Cortez Y, Bittner S, Bittner A, Arshad S, Huang TT, Kraemer FB, Azhar S. SOD2 deficiency-induced oxidative stress attenuates steroidogenesis in mouse ovarian granulosa cells. Mol Cell Endocrinol. 2021 Jan 1;519:110888. doi: 10.1016/j.mce.2020.110888. Epub 2020 Jul 25. PMID: 32717420; PMCID: PMC8011630. 

  14. Azhar S, Shen WJ, Hu Z, Kraemer FB. MicroRNA regulation of adrenal glucocorticoid and androgen biosynthesis. Vitam Horm. 2024;124:1-37. doi: 10.1016/bs.vh.2023.06.006. Epub 2023 Nov 24. PMID: 38408797.