Résumé

Obesity is characterized by an excessive triacylglycerol accumulation in white adipocytes. Various mechanisms allowing the tight regulation of triacylglycerol storage and mobilization by lipid droplet-associated proteins as well as lipolytic enzymes have been identified. Increasing energy expenditure by inducing a mild uncoupling of mitochondria in adipocytes might represent a putative interesting anti-obesity strategy as it reduces the adipose tissue triacylglycerol content (limiting alterations caused by cell hypertrophy) by stimulating lipolysis through yet unknown mechanisms, limiting the adverse effects of adipocyte hypertrophy. Herein, the molecular mechanisms involved in lipolysis induced by a mild uncoupling of mitochondria in white 3T3-L1 adipocytes were characterized. Mitochondrial uncoupling-induced lipolysis was found to be independent from canonical pathways that involve lipolytic enzymes such as HSL and ATGL. Finally, enhanced lipolysis in response to mitochondrial uncoupling relies on a form of autophagy as lipid droplets are captured by endolysosomal vesicles. This new mechanism of triacylglycerol breakdown in adipocytes exposed to mild uncoupling provides new insights on the biology of adipocytes dealing with mitochondria forced to dissipate energy.
langueAnglais
Pages1247-1265
Nombre de pages18
journalJournal of Cellular Physiology
Volume233
Les DOIs
étatPublié - 1 févr. 2018

Empreinte digitale

Lipolysis
Autophagy
Adipocytes
Mitochondria
Triglycerides
Hypertrophy
Lipids
Obesity
White Adipocytes
Enzymes
Energy Metabolism
Tissue
Adipose Tissue
Proteins

mots-clés

    Citer ceci

    @article{70f1b4f099034491afc5f1c4ba8fcd14,
    title = "Mild mitochondrial uncoupling induces HSL/ATGL-independent lipolysis relying on a form of autophagy in 3T3-L1 adipocytes",
    abstract = "Obesity is characterized by an excessive triacylglycerol accumulation in white adipocytes. Various mechanisms allowing the tight regulation of triacylglycerol storage and mobilization by lipid droplet-associated proteins as well as lipolytic enzymes have been identified. Increasing energy expenditure by inducing a mild uncoupling of mitochondria in adipocytes might represent a putative interesting anti-obesity strategy as it reduces the adipose tissue triacylglycerol content (limiting alterations caused by cell hypertrophy) by stimulating lipolysis through yet unknown mechanisms, limiting the adverse effects of adipocyte hypertrophy. Herein, the molecular mechanisms involved in lipolysis induced by a mild uncoupling of mitochondria in white 3T3-L1 adipocytes were characterized. Mitochondrial uncoupling-induced lipolysis was found to be independent from canonical pathways that involve lipolytic enzymes such as HSL and ATGL. Finally, enhanced lipolysis in response to mitochondrial uncoupling relies on a form of autophagy as lipid droplets are captured by endolysosomal vesicles. This new mechanism of triacylglycerol breakdown in adipocytes exposed to mild uncoupling provides new insights on the biology of adipocytes dealing with mitochondria forced to dissipate energy.",
    keywords = "mitochondrial uncoupling; lipolysis; autophagy; HSL; ATGL; adipocytes; lipid metabolism; glycerol",
    author = "St{\'e}phane Demine and {Tejerina Vargas}, {Silvia Veronica} and Beno{\^i}t Bihin and Marc Thiry and Reddy Nagabushana and Patricia Renard and Martine Raes and Michel Jadot and Thierry Arnould",
    year = "2018",
    month = "2",
    day = "1",
    doi = "10.1002/jcp.25994",
    language = "English",
    volume = "233",
    pages = "1247--1265",
    journal = "Journal of Cellular Physiology",
    issn = "0021-9541",
    publisher = "Wiley-Liss Inc.",

    }

    TY - JOUR

    T1 - Mild mitochondrial uncoupling induces HSL/ATGL-independent lipolysis relying on a form of autophagy in 3T3-L1 adipocytes

    AU - Demine,Stéphane

    AU - Tejerina Vargas,Silvia Veronica

    AU - Bihin,Benoît

    AU - Thiry,Marc

    AU - Nagabushana,Reddy

    AU - Renard,Patricia

    AU - Raes,Martine

    AU - Jadot,Michel

    AU - Arnould,Thierry

    PY - 2018/2/1

    Y1 - 2018/2/1

    N2 - Obesity is characterized by an excessive triacylglycerol accumulation in white adipocytes. Various mechanisms allowing the tight regulation of triacylglycerol storage and mobilization by lipid droplet-associated proteins as well as lipolytic enzymes have been identified. Increasing energy expenditure by inducing a mild uncoupling of mitochondria in adipocytes might represent a putative interesting anti-obesity strategy as it reduces the adipose tissue triacylglycerol content (limiting alterations caused by cell hypertrophy) by stimulating lipolysis through yet unknown mechanisms, limiting the adverse effects of adipocyte hypertrophy. Herein, the molecular mechanisms involved in lipolysis induced by a mild uncoupling of mitochondria in white 3T3-L1 adipocytes were characterized. Mitochondrial uncoupling-induced lipolysis was found to be independent from canonical pathways that involve lipolytic enzymes such as HSL and ATGL. Finally, enhanced lipolysis in response to mitochondrial uncoupling relies on a form of autophagy as lipid droplets are captured by endolysosomal vesicles. This new mechanism of triacylglycerol breakdown in adipocytes exposed to mild uncoupling provides new insights on the biology of adipocytes dealing with mitochondria forced to dissipate energy.

    AB - Obesity is characterized by an excessive triacylglycerol accumulation in white adipocytes. Various mechanisms allowing the tight regulation of triacylglycerol storage and mobilization by lipid droplet-associated proteins as well as lipolytic enzymes have been identified. Increasing energy expenditure by inducing a mild uncoupling of mitochondria in adipocytes might represent a putative interesting anti-obesity strategy as it reduces the adipose tissue triacylglycerol content (limiting alterations caused by cell hypertrophy) by stimulating lipolysis through yet unknown mechanisms, limiting the adverse effects of adipocyte hypertrophy. Herein, the molecular mechanisms involved in lipolysis induced by a mild uncoupling of mitochondria in white 3T3-L1 adipocytes were characterized. Mitochondrial uncoupling-induced lipolysis was found to be independent from canonical pathways that involve lipolytic enzymes such as HSL and ATGL. Finally, enhanced lipolysis in response to mitochondrial uncoupling relies on a form of autophagy as lipid droplets are captured by endolysosomal vesicles. This new mechanism of triacylglycerol breakdown in adipocytes exposed to mild uncoupling provides new insights on the biology of adipocytes dealing with mitochondria forced to dissipate energy.

    KW - mitochondrial uncoupling; lipolysis; autophagy; HSL; ATGL; adipocytes; lipid metabolism; glycerol

    U2 - 10.1002/jcp.25994

    DO - 10.1002/jcp.25994

    M3 - Article

    VL - 233

    SP - 1247

    EP - 1265

    JO - Journal of Cellular Physiology

    T2 - Journal of Cellular Physiology

    JF - Journal of Cellular Physiology

    SN - 0021-9541

    ER -