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

iScience (Dec 2021)

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

Affiliations

Julia L. Nugent: Department of Surgery, University of Minnesota, MN, USA; Preclinical Research Center, Department of Surgery, University of Minnesota, 295 Animal Science/Veterinary Medicine Building, 1988 Fitch Avenue, St. Paul, MN 55108, USA
Amar Singh: Department of Surgery, University of Minnesota, MN, USA; Schulze Diabetes Institute, Department of Surgery, University of Minnesota, MN, USA
Keith M. Wirth: Department of Surgery, University of Minnesota, MN, USA
Scott Hunter Oppler: Department of Surgery, University of Minnesota, MN, USA; Preclinical Research Center, Department of Surgery, University of Minnesota, 295 Animal Science/Veterinary Medicine Building, 1988 Fitch Avenue, St. Paul, MN 55108, USA
Laura Hocum Stone: Department of Surgery, University of Minnesota, MN, USA; Preclinical Research Center, Department of Surgery, University of Minnesota, 295 Animal Science/Veterinary Medicine Building, 1988 Fitch Avenue, St. Paul, MN 55108, USA
Jody L. Janecek: Department of Surgery, University of Minnesota, MN, USA; Preclinical Research Center, Department of Surgery, University of Minnesota, 295 Animal Science/Veterinary Medicine Building, 1988 Fitch Avenue, St. Paul, MN 55108, USA
Adam C. Sheka: Department of Surgery, University of Minnesota, MN, USA
Scott Kizy: Department of Surgery, University of Minnesota, MN, USA
Meghan E.G. Moore: Department of Surgery, University of Minnesota, MN, USA; Preclinical Research Center, Department of Surgery, University of Minnesota, 295 Animal Science/Veterinary Medicine Building, 1988 Fitch Avenue, St. Paul, MN 55108, USA
Christopher Staley: Department of Surgery, University of Minnesota, MN, USA; BioTechnology Institute, University of Minnesota, MN, USA
Bernhard J. Hering: Department of Surgery, University of Minnesota, MN, USA; Schulze Diabetes Institute, Department of Surgery, University of Minnesota, MN, USA
Sabarinathan Ramachandran: Department of Surgery, University of Minnesota, MN, USA; Schulze Diabetes Institute, Department of Surgery, University of Minnesota, MN, USA; Corresponding author
Sayeed Ikramuddin: Department of Surgery, University of Minnesota, MN, USA; Corresponding author
Melanie L. Graham: Department of Surgery, University of Minnesota, MN, USA; Preclinical Research Center, Department of Surgery, University of Minnesota, 295 Animal Science/Veterinary Medicine Building, 1988 Fitch Avenue, St. Paul, MN 55108, USA; Corresponding author

Journal volume & issue: Vol. 24, no. 12
p. 103421

Abstract

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Summary: 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.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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