title: Dietary cholesterol promotes adipocyte hypertrophy and adipose tissue inflammation in visceral, but not in subcutaneous, fat in monkeys.
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.
  
  
  RESULTS
  Age-matched, male African Green monkeys (n=5 per group) were assigned to 1 of 3 diets containing 0.002 (low [Lo]), 0.2 (medium [Med]), or 0.4 (high [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 stepwise manner in visceral, but not in subcutaneous fat, with a significant association between visceral adipocyte size and FC content (r(2)=0.298; n=15; P=0.035). In visceral fat, dietary cholesterol intake was associated with (1) increased proinflammatory 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. Visceral fat cells seem to compensate for increased dietary cholesterol by limiting cholesterol uptake/synthesis and increasing FC efflux pathways.
authors: From the Department of Pathology, Sections on Lipid Sciences (S.C., H.C., S.M.M., A.L.M., R.E.T., J.S.P.) and Comparative Medicine (K.K.), and Department of Biochemistry (J.S.P.), Wake Forest School of Medicine, Winston-Salem, NC; Department of Nutrition and Health Sciences, University of Nebraska, Lincoln (S.C.); Department of Food Science and Human Nutrition, University of Florida, Gainesville (S.C., J.-H.H.); and Department of Pathology and Laboratory Medicine, Howard Hughes Medical Institute, University of California, Los Angeles (C.H., P.T.).
authors: Soonkyu
authors: S
authors: Chung
authors: From the Department of Pathology, Sections on Lipid Sciences (S.C., H.C., S.M.M., A.L.M., R.E.T., J.S.P.) and Comparative Medicine (K.K.), and Department of Biochemistry (J.S.P.), Wake Forest School of Medicine, Winston-Salem, NC; Department of Nutrition and Health Sciences, University of Nebraska, Lincoln (S.C.); Department of Food Science and Human Nutrition, University of Florida, Gainesville (S.C., J.-H.H.); and Department of Pathology and Laboratory Medicine, Howard Hughes Medical Institute, University of California, Los Angeles (C.H., P.T.).
authors: Helen
authors: H
authors: Cuffe
authors: From the Department of Pathology, Sections on Lipid Sciences (S.C., H.C., S.M.M., A.L.M., R.E.T., J.S.P.) and Comparative Medicine (K.K.), and Department of Biochemistry (J.S.P.), Wake Forest School of Medicine, Winston-Salem, NC; Department of Nutrition and Health Sciences, University of Nebraska, Lincoln (S.C.); Department of Food Science and Human Nutrition, University of Florida, Gainesville (S.C., J.-H.H.); and Department of Pathology and Laboratory Medicine, Howard Hughes Medical Institute, University of California, Los Angeles (C.H., P.T.).
authors: Stephanie M
authors: SM
authors: Marshall
authors: From the Department of Pathology, Sections on Lipid Sciences (S.C., H.C., S.M.M., A.L.M., R.E.T., J.S.P.) and Comparative Medicine (K.K.), and Department of Biochemistry (J.S.P.), Wake Forest School of Medicine, Winston-Salem, NC; Department of Nutrition and Health Sciences, University of Nebraska, Lincoln (S.C.); Department of Food Science and Human Nutrition, University of Florida, Gainesville (S.C., J.-H.H.); and Department of Pathology and Laboratory Medicine, Howard Hughes Medical Institute, University of California, Los Angeles (C.H., P.T.).
authors: Allison L
authors: AL
authors: McDaniel
authors: From the Department of Pathology, Sections on Lipid Sciences (S.C., H.C., S.M.M., A.L.M., R.E.T., J.S.P.) and Comparative Medicine (K.K.), and Department of Biochemistry (J.S.P.), Wake Forest School of Medicine, Winston-Salem, NC; Department of Nutrition and Health Sciences, University of Nebraska, Lincoln (S.C.); Department of Food Science and Human Nutrition, University of Florida, Gainesville (S.C., J.-H.H.); and Department of Pathology and Laboratory Medicine, Howard Hughes Medical Institute, University of California, Los Angeles (C.H., P.T.).
authors: Jung-Heun
authors: JH
authors: Ha
authors: From the Department of Pathology, Sections on Lipid Sciences (S.C., H.C., S.M.M., A.L.M., R.E.T., J.S.P.) and Comparative Medicine (K.K.), and Department of Biochemistry (J.S.P.), Wake Forest School of Medicine, Winston-Salem, NC; Department of Nutrition and Health Sciences, University of Nebraska, Lincoln (S.C.); Department of Food Science and Human Nutrition, University of Florida, Gainesville (S.C., J.-H.H.); and Department of Pathology and Laboratory Medicine, Howard Hughes Medical Institute, University of California, Los Angeles (C.H., P.T.).
authors: Kylie
authors: K
authors: Kavanagh
authors: From the Department of Pathology, Sections on Lipid Sciences (S.C., H.C., S.M.M., A.L.M., R.E.T., J.S.P.) and Comparative Medicine (K.K.), and Department of Biochemistry (J.S.P.), Wake Forest School of Medicine, Winston-Salem, NC; Department of Nutrition and Health Sciences, University of Nebraska, Lincoln (S.C.); Department of Food Science and Human Nutrition, University of Florida, Gainesville (S.C., J.-H.H.); and Department of Pathology and Laboratory Medicine, Howard Hughes Medical Institute, University of California, Los Angeles (C.H., P.T.).
authors: Cynthia
authors: C
authors: Hong
authors: From the Department of Pathology, Sections on Lipid Sciences (S.C., H.C., S.M.M., A.L.M., R.E.T., J.S.P.) and Comparative Medicine (K.K.), and Department of Biochemistry (J.S.P.), Wake Forest School of Medicine, Winston-Salem, NC; Department of Nutrition and Health Sciences, University of Nebraska, Lincoln (S.C.); Department of Food Science and Human Nutrition, University of Florida, Gainesville (S.C., J.-H.H.); and Department of Pathology and Laboratory Medicine, Howard Hughes Medical Institute, University of California, Los Angeles (C.H., P.T.).
authors: Peter
authors: P
authors: Tontonoz
authors: From the Department of Pathology, Sections on Lipid Sciences (S.C., H.C., S.M.M., A.L.M., R.E.T., J.S.P.) and Comparative Medicine (K.K.), and Department of Biochemistry (J.S.P.), Wake Forest School of Medicine, Winston-Salem, NC; Department of Nutrition and Health Sciences, University of Nebraska, Lincoln (S.C.); Department of Food Science and Human Nutrition, University of Florida, Gainesville (S.C., J.-H.H.); and Department of Pathology and Laboratory Medicine, Howard Hughes Medical Institute, University of California, Los Angeles (C.H., P.T.).
authors: Ryan E
authors: RE
authors: Temel
authors: From the Department of Pathology, Sections on Lipid Sciences (S.C., H.C., S.M.M., A.L.M., R.E.T., J.S.P.) and Comparative Medicine (K.K.), and Department of Biochemistry (J.S.P.), Wake Forest School of Medicine, Winston-Salem, NC; Department of Nutrition and Health Sciences, University of Nebraska, Lincoln (S.C.); Department of Food Science and Human Nutrition, University of Florida, Gainesville (S.C., J.-H.H.); and Department of Pathology and Laboratory Medicine, Howard Hughes Medical Institute, University of California, Los Angeles (C.H., P.T.). jparks@wakehealth.edu ryan.temel@uky.edu.
authors: John S
authors: JS
authors: Parks
mesh_terms: D017667:Adipocytes / Q000187:drug effects* / Q000473:pathology; D000818:Animals; D048429:Cell Size / Q000187:drug effects; D002522:Chlorocebus aethiops; D002784:Cholesterol / Q000032:analysis; D002791:Cholesterol, Dietary / Q000633:toxicity*; D005786:Gene Expression Regulation / Q000187:drug effects; D006984:Hypertrophy; D007249:Inflammation / Q000235:genetics; D050152:Intra-Abdominal Fat / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology; D008074:Lipoproteins / Q000378:metabolism; D008099:Liver / Q000737:chemistry; D008297:Male; D009928:Organ Specificity; D050151:Subcutaneous Fat / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology
chemical_list: D002791:Cholesterol, Dietary; D008074:Lipoproteins; D002784:Cholesterol
keywords: Cercopithecus aethiops; adipose tissue; cholesterol; dietary; inflammation; white