About

Saame "Raz" Shaikh, PhD, is a professor and chair of the Department of Nutrition at the UNC Gillings School of Global Public Health. He has over 10 years of research experience focusing on how dietary fatty acids and their metabolites regulate immunological and metabolic responses in obesity, type 2 diabetes, and cardiovascular diseases. His current research emphasizes understanding how dietary n-3 polyunsaturated fatty acids and their downstream metabolites control infectious, inflammatory, and metabolic responses in obesity and its associated complications. Additionally, Dr. Shaikh is working on strategies to improve mitochondrial function, particularly investigating how modifications to mitochondrial phospholipids like cardiolipin impact oxidative phosphorylation and mitochondrial structure in disease states. He is also conducting clinical studies on how specific dietary fatty acids, such as palmitoleic acid, influence systemic inflammation. Dr. Shaikh's work integrates techniques from lipid biochemistry, membrane biophysics, and nutritional immunology, employing model systems ranging from biomimetic membranes and cell cultures to transgenic mice and human subjects. His contributions have been recognized through awards such as the Early Career Award from ISSFAL in 2012 and the American Society for Nutrition research award in 2018. He has served on the editorial boards of several scientific journals and has been elected to the boards of ISSFAL and ASN, reflecting his leadership in the field of fatty acids and nutrition research.

Research topics

• Medicine
• Biochemistry
• Biology
• Internal medicine
• Endocrinology
• Chemistry
• Genetics
• Biophysics
• Cell biology

Selected publications

• Lysophospholipid acylation modulates plasma membrane lipid organization and insulin sensitivity in skeletal muscle

  Journal of Clinical Investigation · 2021 · 76 citations

  • Internal medicine
  • Endocrinology
  • Biology

  Aberrant lipid metabolism promotes the development of skeletal muscle insulin resistance, but the exact identity of lipid-mediated mechanisms relevant to human obesity remains unclear. A comprehensive lipidomic analysis of primary myocytes from individuals who were insulin-sensitive and lean (LN) or insulin-resistant with obesity (OB) revealed several species of lysophospholipids (lyso-PLs) that were differentially abundant. These changes coincided with greater expression of lysophosphatidylcholine acyltransferase 3 (LPCAT3), an enzyme involved in phospholipid transacylation (Lands cycle). Strikingly, mice with skeletal muscle-specific knockout of LPCAT3 (LPCAT3-MKO) exhibited greater muscle lysophosphatidylcholine/phosphatidylcholine, concomitant with improved skeletal muscle insulin sensitivity. Conversely, skeletal muscle-specific overexpression of LPCAT3 (LPCAT3-MKI) promoted glucose intolerance. The absence of LPCAT3 reduced phospholipid packing of cellular membranes and increased plasma membrane lipid clustering, suggesting that LPCAT3 affects insulin receptor phosphorylation by modulating plasma membrane lipid organization. In conclusion, obesity accelerates the skeletal muscle Lands cycle, whose consequence might induce the disruption of plasma membrane organization that suppresses muscle insulin action.

  PublisherOA PDFDOI

• The cardiolipin-binding peptide elamipretide mitigates fragmentation of cristae networks following cardiac ischemia reperfusion in rats

  Communications Biology · 2020 · 89 citations

  Senior authorCorresponding
  • Cell biology
  • Chemistry
  • Biophysics

  Mitochondrial dysfunction contributes to cardiac pathologies. Barriers to new therapies include an incomplete understanding of underlying molecular culprits and a lack of effective mitochondria-targeted medicines. Here, we test the hypothesis that the cardiolipin-binding peptide elamipretide, a clinical-stage compound under investigation for diseases of mitochondrial dysfunction, mitigates impairments in mitochondrial structure-function observed after rat cardiac ischemia-reperfusion. Respirometry with permeabilized ventricular fibers indicates that ischemia-reperfusion induced decrements in the activity of complexes I, II, and IV are alleviated with elamipretide. Serial block face scanning electron microscopy used to create 3D reconstructions of cristae ultrastructure reveals that disease-induced fragmentation of cristae networks are improved with elamipretide. Mass spectrometry shows elamipretide did not protect against the reduction of cardiolipin concentration after ischemia-reperfusion. Finally, elamipretide improves biophysical properties of biomimetic membranes by aggregating cardiolipin. The data suggest mitochondrial structure-function are interdependent and demonstrate elamipretide targets mitochondrial membranes to sustain cristae networks and improve bioenergetic function.

  DOI

• Resolvin E1 derived from eicosapentaenoic acid prevents hyperinsulinemia and hyperglycemia in a host genetic manner

  The FASEB Journal · 2020 · 58 citations

  Senior authorCorresponding
  • Internal medicine
  • Endocrinology
  • Biology

  Eicosapentaenoic acid (EPA) has garnered attention after the success of the REDUCE-IT trial, which contradicted previous conclusions on EPA for cardiovascular disease risk. Here we first investigated EPA's preventative role on hyperglycemia and hyperinsulinemia. EPA ethyl esters prevented obesity-induced glucose intolerance, hyperinsulinemia, and hyperglycemia in C57BL/6J mice. Supporting NHANES analyses showed that fasting glucose levels of obese adults were inversely related to EPA intake. We next investigated how EPA improved murine hyperinsulinemia and hyperglycemia. EPA overturned the obesity-driven decrement in the concentration of 18-hydroxyeicosapentaenoic acid (18-HEPE) in white adipose tissue and liver. Treatment of obese inbred mice with RvE1, the downstream immunoresolvant metabolite of 18-HEPE, but not 18-HEPE itself, reversed hyperinsulinemia and hyperglycemia through the G-protein coupled receptor ERV1/ChemR23. To translate the findings, we determined if the effects of RvE1 were dependent on host genetics. RvE1's effects on hyperinsulinemia and hyperglycemia were divergent in diversity outbred mice that model human genetic variation. Secondary SNP analyses further confirmed extensive genetic variation in human RvE1/EPA-metabolizing genes. Collectively, the data suggest EPA prevents hyperinsulinemia and hyperglycemia, in part, through RvE1's activation of ERV1/ChemR23 in a host genetic manner. The studies underscore the need for personalized administration of RvE1 based on genetic/metabolic enzyme profiles.

  DOI

Recent grants

• Suppressing inflammation and boosting humoral immunity with n-3 PUFAs

  NIH · $1.9M · 2015–2021

• SPMs, linoleic acid, and antibody levels in obesity

  NIH · $149k · 2021–2023

• Animal Metabolism Phenotyping Core

  NIH · $11.3M · 1999–2027

• NIH Grant R01HL123647

  NIH · $1.4M · 2020

• Dietary DHA mitigates ozone induced pulmonary inflammation

  NIH · $2.9M · 2020–2026

Frequent coauthors

• Ying Zhang

  Circadian (United States)

  83 shared

• William Stillwell

  Indiana University – Purdue University Indianapolis

  82 shared

• Stephen R. Wassall

  University of Indianapolis

  81 shared

• Nichole Reisdorph

  University of Colorado Denver

  42 shared

• William Guesdon

  40 shared

• Miranda Crouch

  University of North Carolina at Chapel Hill

  35 shared

• Rasagna Kosaraju

  East Carolina University

  34 shared

• Edward Ross Pennington

  University of North Carolina at Chapel Hill

  31 shared

Labs

• Shaikh's LabPI

Education

• Ph.D. Medical Biophysics

  Indiana University

  2004

Awards & honors

• Early Career Award 2012, ISSFAL
• Five Year Achievement Award for Excellence in Research and C…
• Mary Swartz Rose Young Investigator Award 2018, American Soc…

Similar researchers at University of North Carolina at Chapel Hill

• Barry M. Popkinh-170
• Cynthia Bulikh-134
• Doug Perkinsh-115
• Paul Watkinsh-107
• Linda Adairh-106