Plasma apolipoprotein B-48 transport in obese men: A new tracer kinetic study in the postprandial state

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    Abstract

    Context: The mechanisms responsible for impaired chylomicron metabolism have not been adequately investigated in obese subjects. Objective: We aimed to compare apolipoprotein (apo) B-48 kinetics in obese and lean men by developing a new model to describe the kinetics of apoB-48 particles in the postprandial state. Design, Setting, and Patients: Seven obese and 13 age-matched lean men were given an oral fat load. apoB-48 tracer to tracee ratios were measured after intravenous d3-leucine administration using gas chromatography-mass spectrometry. Kinetic parameters were derived using a multicompartmental model. Outcomes Measures: Plasma total and incremental apoB-48 0-10 hour areas under the curve as well as apoB-48 secretion and fractional catabolic rate. Results: Compared with lean men, fasting plasma triglyceride (+148%) and apoB-48 (+110%) concentrations as well as plasma total and incremental triglycerides (+184% and +185%, respectively) and apoB-48 (+182% and 224%, respectively) areas under the curve were significantly higher in obese men (P <.05 for all). The obese men also had significantly (P <.05 for all) higher secretion rates of apoB-48 in the fasted state (+145%)as well as at 3 hours (+70%), 4 hours (+82%), 5 hours (+82%), 6 hours (+76%), and 8 hours (+61%) in response to the fat load. This was associated with a greater number of apoB-48-containing particles secreted over the 10-hour study period in the obese men, compared with lean men (+125%, P <.01). The fractional catabolic rate of apoB-48 was significantly lower in the obese men compared with the lean men (-33%, P <.05) Conclusion: We demonstrate that postprandial hypertriglyceridemia in central obesity relates to an overproduction and impaired catabolism of apoB-48-containing lipoproteins. These findings are based on a new, physiologically relevant, kinetic model ,which describes the non-steady-state postprandial metabolism of apoB-48. (J Clin Endocrinol Metab 99: E122-E126, 2014) © Copyright 2014 by The Endocrine Society.
    Original languageEnglish
    Pages (from-to)E122-E126
    JournalJournal of Clinical Endocrinology and Metabolism
    Volume99
    Issue number1
    DOIs
    Publication statusPublished - Jan 2014

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    Apolipoprotein B-48
    Plasmas
    Kinetics
    Metabolism
    Area Under Curve
    Triglycerides
    Fats
    Chylomicrons
    Abdominal Obesity
    Hypertriglyceridemia
    Kinetic parameters
    Leucine
    Gas chromatography
    Gas Chromatography-Mass Spectrometry
    Lipoproteins

    Cite this

    @article{790964f084ef4bf69073d2a30514185e,
    title = "Plasma apolipoprotein B-48 transport in obese men: A new tracer kinetic study in the postprandial state",
    abstract = "Context: The mechanisms responsible for impaired chylomicron metabolism have not been adequately investigated in obese subjects. Objective: We aimed to compare apolipoprotein (apo) B-48 kinetics in obese and lean men by developing a new model to describe the kinetics of apoB-48 particles in the postprandial state. Design, Setting, and Patients: Seven obese and 13 age-matched lean men were given an oral fat load. apoB-48 tracer to tracee ratios were measured after intravenous d3-leucine administration using gas chromatography-mass spectrometry. Kinetic parameters were derived using a multicompartmental model. Outcomes Measures: Plasma total and incremental apoB-48 0-10 hour areas under the curve as well as apoB-48 secretion and fractional catabolic rate. Results: Compared with lean men, fasting plasma triglyceride (+148{\%}) and apoB-48 (+110{\%}) concentrations as well as plasma total and incremental triglycerides (+184{\%} and +185{\%}, respectively) and apoB-48 (+182{\%} and 224{\%}, respectively) areas under the curve were significantly higher in obese men (P <.05 for all). The obese men also had significantly (P <.05 for all) higher secretion rates of apoB-48 in the fasted state (+145{\%})as well as at 3 hours (+70{\%}), 4 hours (+82{\%}), 5 hours (+82{\%}), 6 hours (+76{\%}), and 8 hours (+61{\%}) in response to the fat load. This was associated with a greater number of apoB-48-containing particles secreted over the 10-hour study period in the obese men, compared with lean men (+125{\%}, P <.01). The fractional catabolic rate of apoB-48 was significantly lower in the obese men compared with the lean men (-33{\%}, P <.05) Conclusion: We demonstrate that postprandial hypertriglyceridemia in central obesity relates to an overproduction and impaired catabolism of apoB-48-containing lipoproteins. These findings are based on a new, physiologically relevant, kinetic model ,which describes the non-steady-state postprandial metabolism of apoB-48. (J Clin Endocrinol Metab 99: E122-E126, 2014) {\circledC} Copyright 2014 by The Endocrine Society.",
    author = "A.T.Y. Wong and Dick Chan and Jing Pang and Gerald Watts and Hugh Barrett",
    year = "2014",
    month = "1",
    doi = "10.1210/jc.2013-2477",
    language = "English",
    volume = "99",
    pages = "E122--E126",
    journal = "Journal of Endocrinology & Metabolism",
    issn = "0021-972X",
    publisher = "ENDOCRINE SOC",
    number = "1",

    }

    TY - JOUR

    T1 - Plasma apolipoprotein B-48 transport in obese men: A new tracer kinetic study in the postprandial state

    AU - Wong, A.T.Y.

    AU - Chan, Dick

    AU - Pang, Jing

    AU - Watts, Gerald

    AU - Barrett, Hugh

    PY - 2014/1

    Y1 - 2014/1

    N2 - Context: The mechanisms responsible for impaired chylomicron metabolism have not been adequately investigated in obese subjects. Objective: We aimed to compare apolipoprotein (apo) B-48 kinetics in obese and lean men by developing a new model to describe the kinetics of apoB-48 particles in the postprandial state. Design, Setting, and Patients: Seven obese and 13 age-matched lean men were given an oral fat load. apoB-48 tracer to tracee ratios were measured after intravenous d3-leucine administration using gas chromatography-mass spectrometry. Kinetic parameters were derived using a multicompartmental model. Outcomes Measures: Plasma total and incremental apoB-48 0-10 hour areas under the curve as well as apoB-48 secretion and fractional catabolic rate. Results: Compared with lean men, fasting plasma triglyceride (+148%) and apoB-48 (+110%) concentrations as well as plasma total and incremental triglycerides (+184% and +185%, respectively) and apoB-48 (+182% and 224%, respectively) areas under the curve were significantly higher in obese men (P <.05 for all). The obese men also had significantly (P <.05 for all) higher secretion rates of apoB-48 in the fasted state (+145%)as well as at 3 hours (+70%), 4 hours (+82%), 5 hours (+82%), 6 hours (+76%), and 8 hours (+61%) in response to the fat load. This was associated with a greater number of apoB-48-containing particles secreted over the 10-hour study period in the obese men, compared with lean men (+125%, P <.01). The fractional catabolic rate of apoB-48 was significantly lower in the obese men compared with the lean men (-33%, P <.05) Conclusion: We demonstrate that postprandial hypertriglyceridemia in central obesity relates to an overproduction and impaired catabolism of apoB-48-containing lipoproteins. These findings are based on a new, physiologically relevant, kinetic model ,which describes the non-steady-state postprandial metabolism of apoB-48. (J Clin Endocrinol Metab 99: E122-E126, 2014) © Copyright 2014 by The Endocrine Society.

    AB - Context: The mechanisms responsible for impaired chylomicron metabolism have not been adequately investigated in obese subjects. Objective: We aimed to compare apolipoprotein (apo) B-48 kinetics in obese and lean men by developing a new model to describe the kinetics of apoB-48 particles in the postprandial state. Design, Setting, and Patients: Seven obese and 13 age-matched lean men were given an oral fat load. apoB-48 tracer to tracee ratios were measured after intravenous d3-leucine administration using gas chromatography-mass spectrometry. Kinetic parameters were derived using a multicompartmental model. Outcomes Measures: Plasma total and incremental apoB-48 0-10 hour areas under the curve as well as apoB-48 secretion and fractional catabolic rate. Results: Compared with lean men, fasting plasma triglyceride (+148%) and apoB-48 (+110%) concentrations as well as plasma total and incremental triglycerides (+184% and +185%, respectively) and apoB-48 (+182% and 224%, respectively) areas under the curve were significantly higher in obese men (P <.05 for all). The obese men also had significantly (P <.05 for all) higher secretion rates of apoB-48 in the fasted state (+145%)as well as at 3 hours (+70%), 4 hours (+82%), 5 hours (+82%), 6 hours (+76%), and 8 hours (+61%) in response to the fat load. This was associated with a greater number of apoB-48-containing particles secreted over the 10-hour study period in the obese men, compared with lean men (+125%, P <.01). The fractional catabolic rate of apoB-48 was significantly lower in the obese men compared with the lean men (-33%, P <.05) Conclusion: We demonstrate that postprandial hypertriglyceridemia in central obesity relates to an overproduction and impaired catabolism of apoB-48-containing lipoproteins. These findings are based on a new, physiologically relevant, kinetic model ,which describes the non-steady-state postprandial metabolism of apoB-48. (J Clin Endocrinol Metab 99: E122-E126, 2014) © Copyright 2014 by The Endocrine Society.

    U2 - 10.1210/jc.2013-2477

    DO - 10.1210/jc.2013-2477

    M3 - Article

    VL - 99

    SP - E122-E126

    JO - Journal of Endocrinology & Metabolism

    JF - Journal of Endocrinology & Metabolism

    SN - 0021-972X

    IS - 1

    ER -