title: Biotin-dependent functions in adiposity: a study of monozygotic twin pairs.
abstract: Biotin acts as a coenzyme for carboxylases regulating lipid and amino-acid metabolism. We investigated alterations of the biotin-dependent functions in obesity and the downstream effects of biotin restriction in adipocytes in vitro.
  
  
  
  Twenty-four monozygotic twin pairs discordant for body mass index (BMI). Mean within-pair difference (heavy-lean co-twin, Δ) of BMI was 6.0 kg m(-2) (range 3.1-15.2 kg m(-)(2)).
  
  
  
  Adipose tissue (AT) DNA methylation, gene expression of AT and adipocytes, and leukocytes (real-time quantitative PCR), serum biotin, C-reactive protein (CRP) and triglycerides were measured in the twins. Human adipocytes were cultured in low and control biotin concentrations and analyzed for lipid droplet content, mitochondrial morphology and mitochondrial respiration.
  
  
  
  The gene expression levels of carboxylases, PCCB and MCCC1, were upregulated in the heavier co-twins' leukocytes. ΔPCCB (r=0.91, P=0.0046) and ΔMCCC1 (r=0.79, P=0.036) correlated with ΔCRP within-pairs. Serum biotin levels were lower in the heavier (274 ng l(-1)) than in the lean co-twins (390 ng l(-1), P=0.034). ΔBiotin correlated negatively with Δtriglycerides (r=-0.56, P=0.045) within-pairs. In AT, HLCS and ACACB were hypermethylated and biotin cycle genes HLCS and BTD were downregulated (P<0.05). Biotin-dependent carboxylases were downregulated (ACACA, ACACB, PCCB, MCCC2 and PC; P<0.05) in both AT and adipocytes of the heavier co-twins. Adipocytes cultured in low biotin had decreased lipid accumulation, altered mitochondrial morphology and deficient mitochondrial respiration.
  
  
  
  Biotin-dependent functions are modified by adiposity independent of genetic effects, and correlate with inflammation and hypertriglyceridemia. Biotin restriction decreases lipid accumulation and respiration, and alters mitochondrial morphology in adipocytes.
authors.affiliation: Obesity Research Unit, Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland.
authors.forename: E
authors.initials: E
authors.lastname: Järvinen
authors.affiliation: Department of Public Health, University of Helsinki, Helsinki, Finland.
authors.forename: K
authors.initials: K
authors.lastname: Ismail
authors.affiliation: Obesity Research Unit, Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland.
authors.forename: M
authors.initials: M
authors.lastname: Muniandy
authors.affiliation: Department of Public Health, University of Helsinki, Helsinki, Finland.
authors.forename: L H
authors.initials: LH
authors.lastname: Bogl
authors.affiliation: Obesity Research Unit, Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland.
authors.forename: S
authors.initials: S
authors.lastname: Heinonen
authors.affiliation: Obesity Research Unit, Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland.
authors.forename: M
authors.initials: M
authors.lastname: Tummers
authors.affiliation: BioMediTech, University of Tampere, Tampere, Finland.|Science Center, Tampere University Hospital, Tampere, Finland.
authors.forename: S
authors.initials: S
authors.lastname: Miettinen
authors.affiliation: Department of Public Health, University of Helsinki, Helsinki, Finland.|FIMM, Institute for Molecular Medicine, University of Helsinki, Helsinki, Finland.|Department of Health, National Institute for Health and Welfare, Helsinki, Finland.
authors.forename: J
authors.initials: J
authors.lastname: Kaprio
authors.affiliation: Obesity Research Unit, Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland.|Department of Psychiatry, Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland.
authors.forename: A
authors.initials: A
authors.lastname: Rissanen
authors.affiliation: Department of Public Health, University of Helsinki, Helsinki, Finland.
authors.forename: M
authors.initials: M
authors.lastname: Ollikainen
authors.affiliation: Obesity Research Unit, Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland.|FIMM, Institute for Molecular Medicine, University of Helsinki, Helsinki, Finland.|Abdominal Center, Endocrinology, Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland.
authors.forename: K H
authors.initials: KH
authors.lastname: Pietiläinen
mesh_terms: D017667:Adipocytes / Q000378:metabolism*; D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism*; D050154:Adiposity / Q000235:genetics* / Q000502:physiology*; D000328:Adult; D000596:Amino Acids / Q000235:genetics / Q000378:metabolism; D001710:Biotin / Q000235:genetics / Q000378:metabolism*; D001823:Body Composition / Q000502:physiology; D015992:Body Mass Index; D019175:DNA Methylation / Q000502:physiology; D005260:Female; D006801:Humans; D050356:Lipid Metabolism / Q000235:genetics; D008297:Male; D014430:Twins, Monozygotic / Q000235:genetics*; D055815:Young Adult
chemical_list: D000596:Amino Acids; D001710:Biotin