title: Dynamics of human adipose lipid turnover in health and metabolic disease.
abstract: Adipose tissue mass is determined by the storage and removal of triglycerides in adipocytes. Little is known, however, about adipose lipid turnover in humans in health and pathology. To study this in vivo, here we determined lipid age by measuring (14)C derived from above ground nuclear bomb tests in adipocyte lipids. We report that during the average ten-year lifespan of human adipocytes, triglycerides are renewed six times. Lipid age is independent of adipocyte size, is very stable across a wide range of adult ages and does not differ between genders. Adipocyte lipid turnover, however, is strongly related to conditions with disturbed lipid metabolism. In obesity, triglyceride removal rate (lipolysis followed by oxidation) is decreased and the amount of triglycerides stored each year is increased. In contrast, both lipid removal and storage rates are decreased in non-obese patients diagnosed with the most common hereditary form of dyslipidaemia, familial combined hyperlipidaemia. Lipid removal rate is positively correlated with the capacity of adipocytes to break down triglycerides, as assessed through lipolysis, and is inversely related to insulin resistance. Our data support a mechanism in which adipocyte lipid storage and removal have different roles in health and pathology. High storage but low triglyceride removal promotes fat tissue accumulation and obesity. Reduction of both triglyceride storage and removal decreases lipid shunting through adipose tissue and thus promotes dyslipidaemia. We identify adipocyte lipid turnover as a novel target for prevention and treatment of metabolic disease.
authors.affiliation: Department of Medicine, Karolinska University Hospital, SE-141 86 Stockholm, Sweden. peter.arner@ki.se
authors.forename: Peter
authors.initials: P
authors.lastname: Arner
authors.forename: Samuel
authors.initials: S
authors.lastname: Bernard
authors.forename: Mehran
authors.initials: M
authors.lastname: Salehpour
authors.forename: Göran
authors.initials: G
authors.lastname: Possnert
authors.forename: Jakob
authors.initials: J
authors.lastname: Liebl
authors.forename: Peter
authors.initials: P
authors.lastname: Steier
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Buchholz
authors.forename: Mats
authors.initials: M
authors.lastname: Eriksson
authors.forename: Erik
authors.initials: E
authors.lastname: Arner
authors.forename: Hans
authors.initials: H
authors.lastname: Hauner
authors.forename: Thomas
authors.initials: T
authors.lastname: Skurk
authors.forename: Mikael
authors.initials: M
authors.lastname: Rydén
authors.forename: Keith N
authors.initials: KN
authors.lastname: Frayn
authors.forename: Kirsty L
authors.initials: KL
authors.lastname: Spalding
mesh_terms: D017667:Adipocytes / Q000737:chemistry / Q000378:metabolism; D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002250:Carbon Radioisotopes / Q000032:analysis; D048429:Cell Size; D016922:Cellular Senescence; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004247:DNA / Q000737:chemistry; D050171:Dyslipidemias / Q000378:metabolism / Q000473:pathology; D006262:Health; D006801:Humans; D006950:Hyperlipidemia, Familial Combined / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D050356:Lipid Metabolism; D008066:Lipolysis; D008659:Metabolic Diseases / Q000378:metabolism*; D008875:Middle Aged; D054043:Nuclear Weapons; D009765:Obesity / Q000378:metabolism; D050151:Subcutaneous Fat / Q000378:metabolism; D013997:Time Factors; D014280:Triglycerides / Q000032:analysis / Q000378:metabolism; D055815:Young Adult
chemical_list: D002250:Carbon Radioisotopes; D014280:Triglycerides; D004247:DNA