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White adipose tissue mitochondrial bioenergetics in metabolic diseases

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Abstract

White adipose tissue (WAT) is an important endocrine organ that regulates systemic energy metabolism. In metabolically unhealthy obesity, adipocytes become dysfunctional through hypertrophic mechanisms associated with a reduced endocrine function, reduced mitochondrial function, but increased inflammation, fibrosis, and extracellular remodelling. A pathologic WAT remodelling promotes systemic lipotoxicity characterized by fat accumulation in tissues such as muscle and liver, leading to systemic insulin resistance and type 2 diabetes. Several lines of evidence from human and animal studies suggest a link between unhealthy obesity and adipocyte mitochondrial dysfunction, and interventions that improve mitochondrial function may reduce the risk of obesity-associated diseases. This review discusses the importance of mitochondrial function and metabolism in human adipocyte biology and intercellular communication mechanisms within WAT. Moreover, a selected interventional approach for better adipocyte mitochondrial metabolism in humans is reviewed. A greater understanding of mitochondrial bioenergetics in WAT might provide novel therapeutic opportunities to prevent or restore dysfunctional adipose tissue in obesity-associated diseases.

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Abbreviations

APCs:

Adipose progenitor cells

AT:

Adipose tissue

C/EBPα:

CCAAT-enhancer-binding protein alpha

CREB:

cAMP response element-binding protein

ERRα:

Estrogen-related receptor alpha

ETC:

Electron transport chain

EV:

Extracellular vesicle

HFD:

High-fat diet

PPARγ:

Peroxisome proliferator-activated receptor gamma,

PPARGC1A:

Peroxisome proliferator-activated receptor gamma coactivator 1-alpha

OXPHOS:

Oxidative phosphorylation

SAT:

Subcutaneous white adipose tissue

SVF:

Stromal vascular fraction cells

T2D:

Type 2 diabetes

VAT:

Visceral adipose tissue

WAT:

White adipose tissue

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Acknowledgements

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Funding

RS. and DRH. are supported by the Steno Diabetes Center Odense funded by the Novo Nordisk Foundation.

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  1. Rugivan Sabaratnam and Didde Riisager Hansen contributed equally to this work.

Authors and Affiliations

  1. Department of Clinical Research, University of Southern Denmark, Odense C, DK-5000, Denmark

    Rugivan Sabaratnam

  2. Steno Diabetes Center Odense, Odense University Hospital, Odense C, DK-5000, Denmark

    Rugivan Sabaratnam & Didde Riisager Hansen

  3. Department of Molecular Medicine, Cardiovascular and Renal Research, University of Southern Denmark, J. B. Winsløws Vej 21,3, Odense C, DK-5000, Denmark

    Rugivan Sabaratnam, Didde Riisager Hansen & Per Svenningsen

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  1. Rugivan Sabaratnam
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Conceptualization - RS., DRH., PS.; Writing—original draft preparation, RS., DRH., PS.; Writing—review and editing, RS., DRH., PS.; Visualization - RS., DRH., PS.

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Sabaratnam, R., Hansen, D.R. & Svenningsen, P. White adipose tissue mitochondrial bioenergetics in metabolic diseases. Rev Endocr Metab Disord 24, 1121–1133 (2023). https://doi.org/10.1007/s11154-023-09827-z

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