A nonhuman primate model of vertical sleeve gastrectomy facilitates mechanistic and translational research in human obesity

Julia L. Nugent, Amar Singh, Keith M. Wirth, Scott Hunter Oppler, Laura Hocum Stone, Jody L. Janecek, Adam C. Sheka, Scott Kizy, Meghan E.G. Moore, Christopher Staley, Bernhard J. Hering, Sabarinathan Ramachandran, Sayeed Ikramuddin, Melanie L. Graham

Research output: Contribution to journalArticlepeer-review

Abstract

The obesity epidemic significantly contributes to overall morbidity and mortality. Bariatric surgery is the gold standard treatment for obesity and metabolic dysfunction, yet the mechanisms by which it exerts metabolic benefit remain unclear. Here, we demonstrate a model of vertical sleeve gastrectomy (VSG) in nonhuman primates (NHP) that mimics the complexity and outcomes in humans. We also show that VSG confers weight loss and durable metabolic benefit, where equivalent caloric intake in shams resulted in significant weight gain following surgery. Furthermore, we show that VSG is associated with early, weight-independent increases in bile acids, short-chain fatty acids, and reduced visceral adipose tissue (VAT) inflammation with a polarization of VAT-resident immunocytes toward highly regulatory myeloid cells and Tregs. These data demonstrate that this strongly translational NHP model can be used to interrogate factors driving successful intervention to unravel the interplay between physiologic systems and improve therapies for obesity and metabolic syndrome.

Original languageEnglish (US)
Article number103421
JournaliScience
Volume24
Issue number12
DOIs
StatePublished - Dec 17 2021

Bibliographical note

Funding Information:
We gratefully acknowledge the excellent and expert care, husbandry, and training of our animals by the team at the University of Minnesota's Preclinical Research Center. We thank Dr. Michael Goldberg of the University of Minnesota for planning and performance of conventional flow cytometry. We thank the University of Minnesota Comparative Pathology Shared Resource for processing and preparation of histological sections. This work was funded by endowments from the Jay Phillips Chair and the Robert and Katherine Goodale Chair in Minimally Invasive Surgery, as well as using resources from the University of Minnesota Clinical Immersion Program.

Funding Information:
We gratefully acknowledge the excellent and expert care, husbandry, and training of our animals by the team at the University of Minnesota's Preclinical Research Center. We thank Dr. Michael Goldberg of the University of Minnesota for planning and performance of conventional flow cytometry. We thank the University of Minnesota Comparative Pathology Shared Resource for processing and preparation of histological sections. This work was funded by endowments from the Jay Phillips Chair and the Robert and Katherine Goodale Chair in Minimally Invasive Surgery, as well as using resources from the University of Minnesota Clinical Immersion Program. Conceptualization: MLG, SI, SK, JLN, SR, AS (flow cytometry and CyTOF), KMW. Validation: MLG, JLN, SR, AS (developed/validated 36 metal-tagged antibodies for use in macaques), Methodology: MLG, SHO, SI, JLJ, SK, JLN, SR, AS, and BH (protocol development/optimization for tissue digestion and SVF harvest from AT), KMW. Analysis and investigation: MLG, BH, SI, JLJ, JLN, SK, SHO, SR, AS (CyTOF and conventional flow dataset generation/analysis), CS, KMW. Visualization: JLN, SHO, AS (CyTOF), LHS, KMW. Funding acquisition: MLG, SI. Project administration: MLG, JLJ. Supervision: MLG, SI, SR. Writing ? original draft: JLN, ACS, AS (CyTOF), KMW. Writing ? review & editing: MLG, BH, SI, JLN, SHO, SR, AS, LHS. The authors declare no competing interests. One or more of the authors of this paper self-identifies as an underrepresented ethnic minority in science. One or more of the authors of this paper self-identifies as a member of the LGBTQ+ community.

Publisher Copyright:
© 2021 The Author(s)

Keywords

  • Immunology
  • Obesity medicine
  • Surgery

PubMed: MeSH publication types

  • Journal Article

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