Dietary Cholesterol Promotes Adipocyte Hypertrophy and Adipose Tissue Inflammation in Visceral, But Not Subcutaneous, Fat in Monkeys

Authors

Soonkyu Chung, University of Nebraska-LincolnFollow
Helen Cuffe, Departments of Pathology/Section on Lipid Sciences, Winston-Salem, NC
Stephanie M. Marshall, Departments of Pathology/Section on Lipid Sciences, Winston-Salem, NC
Allison L. McDaniel, Departments of Pathology/Section on Lipid Sciences, Winston-Salem, NC
Jung-Heun Ha, Department of Food Science and Human Nutrition, University of Florida, Gainsville, FL
Kylie Kavanagh, Section on Comparative Medicine, Winston-Salem, NC
Cynthia Hong, Department of Pathology and Laboratory Medicine, Howard Hughes Medical Institute, University of California Los Angeles, Los Angeles, CA
Peter Tontonoz, Department of Pathology and Laboratory Medicine, Howard Hughes Medical Institute, University of California Los Angeles, Los Angeles, CA
Ryan E. Temel, Departments of Pathology/Section on Lipid Sciences, Winston-Salem, NCFollow
John S. Parks, Departments of Pathology/Section on Lipid Sciences, Winston-Salem, NCFollow

Document Type

Article

Date of this Version

2014

Citation

Arterioscler Thromb Vasc Biol. 2014 September ; 34(9): 1880–1887.

Comments

Used by permission.

Abstract

Objective—Excessive caloric intake is associated with obesity and adipose tissue dysfunction. However, the role of dietary cholesterol in this process is unknown. The aim of this study was to determine whether increasing dietary cholesterol intake alters adipose tissue cholesterol content, adipocyte size, and endocrine function in nonhuman primates.

Approach and Results—Age-matched, male African Green monkeys (n=5 per group) were assigned to one of three diets containing 0.002 (Lo), 0.2 (Med) or 0.4 (Hi) mg cholesterol/Kcal. After 10 weeks of diet feeding, animals were euthanized for adipose tissue, liver, and plasma collection. With increasing dietary cholesterol, free cholesterol (FC) content and adipocyte size increased in a step-wise manner in visceral, but not subcutaneous fat, with a significant association between visceral adipocyte size and FC content (r²=0.298; n=15; p=0.035). In visceral fat, dietary cholesterol intake was associated with: 1) increased pro-inflammatory gene expression and macrophage recruitment, 2) decreased expression of genes involved in cholesterol biosynthesis and lipoprotein uptake, and 3) increased expression of proteins involved in FC efflux.

Conclusions—Increasing dietary cholesterol selectively increases visceral fat adipocyte size, FC and macrophage content, and proinflammatory gene expression in nonhuman primates.