title: Differential contribution of dietary fat and monosaccharide to metabolic syndrome in the common marmoset (Callithrix jacchus).
abstract: There is a critical need for animal models to study aspects type 2 diabetes (T2D) pathogenesis and prevention. While the rhesus macaque is such an established model, the common marmoset has added benefits including reduced zoonotic risks, shorter life span, and a predisposition to birth twins demonstrating chimerism. The marmoset as a model organism for the study of metabolic syndrome has not been fully evaluated. Marmosets fed high-fat or glucose-enriched diets were followed longitudinally to observe effects on morphometric and metabolic measures. Effects on pancreatic histomorphometry and vascular pathology were examined terminally. The glucose-enriched diet group developed an obese phenotype and a prolonged hyperglycemic state evidenced by a rapid and persistent increase in mean glycosylated hemoglobin (HgbA1c) observed as early as week 16. In contrast, marmosets fed a high-fat diet did not maintain an obese phenotype and demonstrated a delayed increase in HgbA1) that did not reach statistical significance until week 40. Consumption of either diet resulted in profound pancreatic islet hyperplasia suggesting a compensation for increased insulin requirements. Although the high-fat diet group developed atherosclerosis of increased severity, the presence of lesions correlated with glucose intolerance only in the glucose-enriched diet group. The altered timing of glucose dysregulation, differential contribution to obesity, and variation in vascular pathology suggests mechanisms of effect specific to dietary nutrient content. Feeding nutritionally modified diets to common marmosets recapitulates aspects of metabolic disease and represents a model that may prove instrumental to elucidating the contribution of nutrient excess to disease development.
authors.affiliation: Harvard Medical School, New England Primate Research Center, Southborough, Massachusetts, USA. Lynn_wachtman@hms.harvard.edu
authors.forename: Lynn M
authors.initials: LM
authors.lastname: Wachtman
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Kramer
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Miller
authors.forename: Audra M
authors.initials: AM
authors.lastname: Hachey
authors.forename: Elizabeth H
authors.initials: EH
authors.lastname: Curran
authors.forename: Keith G
authors.initials: KG
authors.lastname: Mansfield
mesh_terms: D000818:Animals; D001158:Arteries / Q000473:pathology; D050197:Atherosclerosis / Q000209:etiology; D001823:Body Composition; D002144:Callithrix; D004040:Dietary Carbohydrates / Q000009:adverse effects*; D004041:Dietary Fats / Q000009:adverse effects*; D004195:Disease Models, Animal; D005260:Female; D018149:Glucose Intolerance / Q000209:etiology; D006442:Glycated Hemoglobin / Q000032:analysis; D006943:Hyperglycemia / Q000209:etiology; D006965:Hyperplasia / Q000209:etiology; D007515:Islets of Langerhans / Q000473:pathology; D008297:Male; D024821:Metabolic Syndrome / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009005:Monosaccharides / Q000009:adverse effects*; D009765:Obesity / Q000209:etiology; D011897:Random Allocation; D012720:Severity of Illness Index; D013997:Time Factors
chemical_list: D004040:Dietary Carbohydrates; D004041:Dietary Fats; D006442:Glycated Hemoglobin; D009005:Monosaccharides