In mammals, the white adipocyte is a cell type that is specialized for storage of energy (in the form of triacylglycerols) and for energy mobilization (as fatty acids). White adipocyte metabolism confers an essential role to adipose tissue in whole-body homeostasis. Dysfunction in white adipocyte metabolism is a cardinal event in the development of insulin resistance and associated disorders. This Review focuses on our current understanding of lipid and glucose metabolic pathways in the white adipocyte. We survey recent advances in humans on the importance of adipocyte hypertrophy and on the in vivo turnover of adipocytes and stored lipids. At the molecular level, the identification of novel regulators and of the interplay between metabolic pathways explains the fine-tuning between the anabolic and catabolic fates of fatty acids and glucose in different physiological states. We also examine the metabolic alterations involved in the genesis of obesity-associated metabolic disorders, lipodystrophic states, cancers and cancer-associated cachexia. New challenges include defining the heterogeneity of white adipocytes in different anatomical locations throughout the lifespan and investigating the importance of rhythmic processes. Targeting white fat metabolism offers opportunities for improved patient stratification and a wide, yet unexploited, range of therapeutic opportunities.
White adipocyte size and turnover are determinants of systemic insulin sensitivity and cardiometabolic phenotype in humans.
White adipocytes are specialized in fat storage and mobilization; the underlying lipid metabolic pathways are tightly connected with those governing the intracellular fate of glucose.
In some fat depots, there is a bidirectional switch between white and beige adipocytes, which display an oxidative phenotype with energy dissipation through uncoupling protein 1 (UCP1)-dependent and UCP1-independent pathways.
White adipocyte metabolic pathways control the secretion of proteins and lipids with local and systemic effects on inflammation and insulin sensitivity.
Adipocyte metabolism offers promising targets for the treatment of cardiometabolic diseases and cancer-associated disorders.
Future research will include the in-depth characterization of adipocyte diversity associated with anatomical location, age, sex and physiological rhythms.
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The rapid growth of research in adipocyte metabolism made it impossible to cite a large number of excellent studies relevant to the topic of this review. D.L. is supported by Inserm, Paul Sabatier University, European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (SPHERES, ERC Synergy Grant agreement No. 856404), Fondation pour la Recherche Médicale (DEQ20170336720), Agence Nationale de la Recherche (ANR-17-CE14-0015Hepadialogue), Région Occitanie (DIALOGUE projects), FORCE/F-CRIN and AstraZeneca France. D.L. is a member of Institut Universitaire de France.
J.B. is an employee of AstraZeneca. The other authors declare no competing interests.
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- Adipose tissue hypertrophy
Adipose tissue expansion through an increase in adipocyte size.
- Adipose tissue hyperplasia
Adipose tissue expansion through the generation of new adipocytes.
- M1-like macrophage
Subtype of macrophages characterized by the secretion of pro-inflammatory cytokines and chemokines, such as IL-6 and tumour necrosis factor.
Triacylglycerol hydrolysis by lysosomal acid lipases after engulfment of a lipid droplet by an autophagosome, which fuses with lysosomes.
- Beige adipocytes
Also known as brown-in-white (brite) adipocytes. A subtype of thermogenic adipocytes located in white fat depots and uniquely equipped to dissipate energy as heat.
- Pyroptotic cell death
Cell death triggered by pro-inflammatory signals and subsequent activation of the NLRP3 inflammasome.
Small extracellular proteins that are responsible for the transport of hydrophobic molecules, such as lipids, steroids and retinoids, in the circulation.
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Morigny, P., Boucher, J., Arner, P. et al. Lipid and glucose metabolism in white adipocytes: pathways, dysfunction and therapeutics. Nat Rev Endocrinol 17, 276–295 (2021). https://doi.org/10.1038/s41574-021-00471-8
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