title: Potential role of milk fat globule membrane in modulating plasma lipoproteins, gene expression, and cholesterol metabolism in humans: a randomized study.
abstract: BACKGROUND
  Butter is rich in saturated fat [saturated fatty acids (SFAs)] and can increase plasma low density lipoprotein (LDL) cholesterol, which is a major risk factor for cardiovascular disease. However, compared with other dairy foods, butter is low in milk fat globule membrane (MFGM) content, which encloses the fat. We hypothesized that different dairy foods may have distinct effects on plasma lipids because of a varying content of MFGM.
  
  
  OBJECTIVE
  We aimed to investigate whether the effects of milk fat on plasma lipids and cardiometabolic risk markers are modulated by the MFGM content.
  
  
  METHODS
  The study was an 8-wk, single-blind, randomized, controlled isocaloric trial with 2 parallel groups including overweight men and women (n = 57 randomly assigned). For the intervention, subjects consumed 40 g milk fat/d as either whipping cream (MFGM diet) or butter oil (control diet). Intervention foods were matched for total fat, protein, carbohydrates, and calcium. Subjects were discouraged from consuming any other dairy products during the study. Plasma markers of cholesterol absorption and hepatic cholesterol metabolism were assessed together with global gene-expression analyses in peripheral blood mononuclear cells.
  
  
  RESULTS
  As expected, the control diet increased plasma lipids, whereas the MFGM diet did not [total cholesterol (±SD): +0.30 ± 0.49 compared with -0.04 ± 0.49 mmol/L, respectively (P = 0.024); LDL cholesterol: +0.36 ± 0.50 compared with +0.04 ± 0.36 mmol/L, respectively (P = 0.024); apolipoprotein B:apolipoprotein A-I ratio: +0.03 ± 0.09 compared with -0.05 ± 0.10 mmol/L, respectively (P = 0.007); and non-HDL cholesterol: +0.24 ± 0.49 compared with -0.14 ± 0.51 mmol/L, respectively (P = 0.013)]. HDL-cholesterol, triglyceride, sitosterol, lathosterol, campesterol, and proprotein convertase subtilisin/kexin type 9 plasma concentrations and fatty acid compositions did not differ between groups. Nineteen genes were differentially regulated between groups, and these genes were mostly correlated with lipid changes.
  
  
  CONCLUSIONS
  In contrast to milk fat without MFGM, milk fat enclosed by MFGM does not impair the lipoprotein profile. The mechanism is not clear although suppressed gene expression by MFGM correlated inversely with plasma lipids. The food matrix should be considered when evaluating cardiovascular aspects of different dairy foods. This trial was registered at clinicaltrials.gov as NCT01767077.
authors.affiliation: Clinical Nutrition and Metabolism, Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden;
authors.forename: Fredrik
authors.initials: F
authors.lastname: Rosqvist
authors.affiliation: Clinical Nutrition and Metabolism, Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden; Dairy Sweden, Stockholm, Sweden;
authors.forename: Annika
authors.initials: A
authors.lastname: Smedman
authors.affiliation: Department of Food Technology, Engineering and Nutrition, Lund University, Lund, Sweden; Dairy Sweden, Stockholm, Sweden;
authors.forename: Helena
authors.initials: H
authors.lastname: Lindmark-Månsson
authors.affiliation: Department of Food Technology, Engineering and Nutrition, Lund University, Lund, Sweden;
authors.forename: Marie
authors.initials: M
authors.lastname: Paulsson
authors.affiliation: Department of Medicine, Karolinska Institute, Huddinge, Sweden.
authors.forename: Paul
authors.initials: P
authors.lastname: Petrus
authors.affiliation: Metabolism Unit, Department of Endocrinology, Metabolism and Diabetes, and KI/AZ Integrated CardioMetabolic Center, Department of Medicine, and Molecular Nutrition Unit, Center for Innovative Medicine, Department of Biosciences and Nutrition, Karolinska Institute, Stockholm, Sweden; and.
authors.forename: Sara
authors.initials: S
authors.lastname: Straniero
authors.affiliation: Metabolism Unit, Department of Endocrinology, Metabolism and Diabetes, and KI/AZ Integrated CardioMetabolic Center, Department of Medicine, and Molecular Nutrition Unit, Center for Innovative Medicine, Department of Biosciences and Nutrition, Karolinska Institute, Stockholm, Sweden; and.
authors.forename: Mats
authors.initials: M
authors.lastname: Rudling
authors.affiliation: Department of Medicine, Karolinska Institute, Huddinge, Sweden.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Dahlman
authors.affiliation: Clinical Nutrition and Metabolism, Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden; ulf.riserus@pubcare.uu.se.
authors.forename: Ulf
authors.initials: U
authors.lastname: Risérus
mesh_terms: D000328:Adult; D000368:Aged; D016632:Apolipoprotein A-I / Q000097:blood; D001055:Apolipoproteins B / Q000097:blood; D015992:Body Mass Index; D002784:Cholesterol / Q000031:analogs & derivatives / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood*; D008078:Cholesterol, LDL / Q000097:blood*; D003611:Dairy Products / Q000032:analysis; D002149:Energy Intake; D005227:Fatty Acids / Q000008:administration & dosage / Q000097:blood; D005247:Feeding Behavior; D005260:Female; D015870:Gene Expression; D006017:Glycolipids / Q000008:administration & dosage*; D006023:Glycoproteins / Q000008:administration & dosage*; D064368:Healthy Volunteers; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D066292:Lipid Droplets; D008297:Male; D008875:Middle Aged; D015596:Nutrition Assessment; D010840:Phytosterols / Q000097:blood; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases / Q000235:genetics / Q000378:metabolism; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism; D016037:Single-Blind Method; D012855:Sitosterols / Q000097:blood; D014280:Triglycerides / Q000097:blood*; D055815:Young Adult
chemical_list: D016632:Apolipoprotein A-I; D001055:Apolipoproteins B; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D005227:Fatty Acids; D006017:Glycolipids; D006023:Glycoproteins; D010840:Phytosterols; D012855:Sitosterols; D014280:Triglycerides; C110367:milk fat globule; C021273:campesterol; C025473:gamma-sitosterol; C001521:lathosterol; D002784:Cholesterol; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases
keywords: MFGM; cholesterol; lipoproteins; milk fat globule membrane; saturated fat