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Integrative Biology

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

International Journal of Obesity volume 40, pages 788–795 (2016)Cite this article

Subjects

Abstract

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. 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.

Conclusions:

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.

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Acknowledgements

We want to thank all the volunteers for their valuable contribution, staff members of the Obesity Research Unit, especially Saila Saarinen, Mia Urjansson, Katja Sohlo and Miia Juntunen and Anna-Maija Honkala for technical assistance, Mervi Lindman from the Electron microscopy unit at the Institute of Biotechnology and Jussi Kenkkilä from the Biomedicum Imaging Unit for technical expertise and Uwe Richter for scientific advise. This study was supported by Helsinki University Hospital Research Funds and grants from the Novo Nordisk Foundation (KP), Diabetes Research Foundation (KP, SH), Jalmari and Rauha Ahokas Foundation (KP, LB), Orion Pharmos Foundation (SH), Emil Aaltonen Foundation (SH), Finnish Medical Foundation (SH), Finnish Foundation for Cardiovascular Research (KP), Finnish Funding Agency for Innovation (SM), Sigrid Juselius Foundation (MO), University of Helsinki Funds 490139 (MO), and Academy of Finland (265240, 263278 (JK), 251316 (MO), EPITRAIN - FP7-PEOPLE-2012-ITN, grant agreement 316758 (JK, MO) and 266286 and 272376 (KP).

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Authors and Affiliations

  1. Obesity Research Unit, Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland

    E Järvinen, M Muniandy, S Heinonen, M Tummers, A Rissanen & K H Pietiläinen

  2. Department of Public Health, University of Helsinki, Helsinki, Finland

    K Ismail, L H Bogl, J Kaprio & M Ollikainen

  3. BioMediTech, University of Tampere, Tampere, Finland

    S Miettinen

  4. Science Center, Tampere University Hospital, Tampere, Finland

    S Miettinen

  5. FIMM, Institute for Molecular Medicine, University of Helsinki, Helsinki, Finland

    J Kaprio & K H Pietiläinen

  6. Department of Health, National Institute for Health and Welfare, Helsinki, Finland

    J Kaprio

  7. Department of Psychiatry, Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland

    A Rissanen

  8. Abdominal Center, Endocrinology, Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland

    K H Pietiläinen

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  1. E Järvinen
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  2. K Ismail
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Correspondence to E Järvinen.

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Järvinen, E., Ismail, K., Muniandy, M. et al. Biotin-dependent functions in adiposity: a study of monozygotic twin pairs. Int J Obes 40, 788–795 (2016). https://doi.org/10.1038/ijo.2015.237

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