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.

Bioscience Metabolism Research and Early Development Cardiovascular Renal and Metabolism BioPharmaceuticals R and D AstraZeneca Gothenburg Sweden

Department of Medicine Karolinska Institutet Stockholm Sweden

Franco Czech Laboratory for Clinical Research on Obesity 3rd Faculty of Medicine Prague and Paul Sabatier University Toulouse France

German Center for Diabetes Research Neuherberg Germany

Institute for Diabetes and Cancer Helmholtz Center Munich Neuherberg Germany

Institute of Metabolic and Cardiovascular Diseases UMR1297 Toulouse France

Joint Heidelberg IDC Translational Diabetes Program Inner Medicine 1 Heidelberg University Hospital Heidelberg Germany

The Lundberg Laboratory for Diabetes Research University of Gothenburg Gothenburg Sweden

Toulouse University Hospitals Laboratory of Clinical Biochemistry Toulouse France

University of Toulouse Paul Sabatier University I2MC UMR1297 Toulouse France

Wallenberg Centre for Molecular and Translational Medicine University of Gothenburg Gothenburg Sweden

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