Biotin-dependent functions in adiposity: a study of monozygotic twin pairs

• Published in: International Journal of Obesity 2016-05, Vol.40 (5), p.788-795
• Main Authors: Järvinen, E, Ismail, K, Muniandy, M, Bogl, L H, Heinonen, S, Tummers, M, Miettinen, S, Kaprio, J, Rissanen, A, Ollikainen, M, Pietiläinen, K H
• Format: Article
• Language: English
• Subjects: 14/19; 14/28; 14/34; 14/63; 45/22; 45/90; 631/208/199; 631/45/607; 631/80; 692/699/2743/393; Accumulation; Adipocytes; Adipocytes - metabolism; Adipose tissue; Adipose Tissue - cytology; Adipose Tissue - metabolism; Adiposity - genetics; Adiposity - physiology; Adult; Amino acids; Amino Acids - genetics; Amino Acids - metabolism; Biotin; Biotin - genetics; Biotin - metabolism; Body Composition - physiology; Body fat; Body Mass Index; Body size; C-reactive protein; Care and treatment; Correlation; Diabetes; DNA methylation; DNA Methylation - physiology; Epidemiology; Epigenetics; Fat cells; Fatty acids; Female; Gene expression; Genetic aspects; Genetic effects; Glucose; Health aspects; Health Promotion and Disease Prevention; Humans; Hypertriglyceridemia; Internal Medicine; Leukocytes; Lipid metabolism; Lipid Metabolism - genetics; Lipids; Male; Medicine; Medicine & Public Health; Metabolic Diseases; Metabolism; Mitochondria; Morphology; Obesity; original-article; Oxidation; Public Health; Respiration; Triglycerides; Twins; Twins, Monozygotic - genetics; Young Adult
• ISSN: 0307-0565; 1476-5497
• DOI: 10.1038/ijo.2015.237

Background: 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 . Subjects: 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 ). Methods: 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. Results: The gene expression levels of carboxylases, PCCB and MCCC1 , were upregulated in the heavier co-twins’ leukocytes. Δ PCCB ( r =0.91, P =0.0046) and Δ MCCC 1 ( 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