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
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.
