title: Dissecting adipose tissue lipolysis: molecular regulation and implications for metabolic disease.
abstract: Lipolysis is the process by which triglycerides (TGs) are hydrolyzed to free fatty acids (FFAs) and glycerol. In adipocytes, this is achieved by sequential action of adipose TG lipase (ATGL), hormone-sensitive lipase (HSL), and monoglyceride lipase. The activity in the lipolytic pathway is tightly regulated by hormonal and nutritional factors. Under conditions of negative energy balance such as fasting and exercise, stimulation of lipolysis results in a profound increase in FFA release from adipose tissue (AT). This response is crucial in order to provide the organism with a sufficient supply of substrate for oxidative metabolism. However, failure to efficiently suppress lipolysis when FFA demands are low can have serious metabolic consequences and is believed to be a key mechanism in the development of type 2 diabetes in obesity. As the discovery of ATGL in 2004, substantial progress has been made in the delineation of the remarkable complexity of the regulatory network controlling adipocyte lipolysis. Notably, regulatory mechanisms have been identified on multiple levels of the lipolytic pathway, including gene transcription and translation, post-translational modifications, intracellular localization, protein-protein interactions, and protein stability/degradation. Here, we provide an overview of the recent advances in the field of AT lipolysis with particular focus on the molecular regulation of the two main lipases, ATGL and HSL, and the intracellular and extracellular signals affecting their activity.
authors.affiliation: The Novo Nordisk Foundation Center for Basic Metabolic ResearchSection on Integrative Physiology, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3b, 6.6.30, DK-2200 N Copenhagen, DenmarkDepartment of Endocrinology and Internal MedicineAarhus University Hospital, Nørrebrogade 44, Bldg. 3.0, 8000 Aarhus C, DenmarkDepartment of Molecular MedicineAarhus University Hospital, Brendstrupgårdsvej 100, 8200 Aarhus N, DenmarkThe Novo Nordisk Foundation Center for Basic Metabolic ResearchSection on Integrative Physiology, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3b, 6.6.30, DK-2200 N Copenhagen, DenmarkDepartment of Endocrinology and Internal MedicineAarhus University Hospital, Nørrebrogade 44, Bldg. 3.0, 8000 Aarhus C, DenmarkDepartment of Molecular MedicineAarhus University Hospital, Brendstrupgårdsvej 100, 8200 Aarhus N, Denmark thomas.nielsen@sund.ku.dk.
authors.forename: Thomas Svava
authors.initials: TS
authors.lastname: Nielsen
authors.affiliation: The Novo Nordisk Foundation Center for Basic Metabolic ResearchSection on Integrative Physiology, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3b, 6.6.30, DK-2200 N Copenhagen, DenmarkDepartment of Endocrinology and Internal MedicineAarhus University Hospital, Nørrebrogade 44, Bldg. 3.0, 8000 Aarhus C, DenmarkDepartment of Molecular MedicineAarhus University Hospital, Brendstrupgårdsvej 100, 8200 Aarhus N, DenmarkThe Novo Nordisk Foundation Center for Basic Metabolic ResearchSection on Integrative Physiology, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3b, 6.6.30, DK-2200 N Copenhagen, DenmarkDepartment of Endocrinology and Internal MedicineAarhus University Hospital, Nørrebrogade 44, Bldg. 3.0, 8000 Aarhus C, DenmarkDepartment of Molecular MedicineAarhus University Hospital, Brendstrupgårdsvej 100, 8200 Aarhus N, Denmark.
authors.forename: Niels
authors.initials: N
authors.lastname: Jessen
authors.affiliation: The Novo Nordisk Foundation Center for Basic Metabolic ResearchSection on Integrative Physiology, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3b, 6.6.30, DK-2200 N Copenhagen, DenmarkDepartment of Endocrinology and Internal MedicineAarhus University Hospital, Nørrebrogade 44, Bldg. 3.0, 8000 Aarhus C, DenmarkDepartment of Molecular MedicineAarhus University Hospital, Brendstrupgårdsvej 100, 8200 Aarhus N, Denmark.
authors.forename: Jens Otto L
authors.initials: JO
authors.lastname: Jørgensen
authors.affiliation: The Novo Nordisk Foundation Center for Basic Metabolic ResearchSection on Integrative Physiology, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3b, 6.6.30, DK-2200 N Copenhagen, DenmarkDepartment of Endocrinology and Internal MedicineAarhus University Hospital, Nørrebrogade 44, Bldg. 3.0, 8000 Aarhus C, DenmarkDepartment of Molecular MedicineAarhus University Hospital, Brendstrupgårdsvej 100, 8200 Aarhus N, Denmark.
authors.forename: Niels
authors.initials: N
authors.lastname: Møller
authors.affiliation: The Novo Nordisk Foundation Center for Basic Metabolic ResearchSection on Integrative Physiology, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3b, 6.6.30, DK-2200 N Copenhagen, DenmarkDepartment of Endocrinology and Internal MedicineAarhus University Hospital, Nørrebrogade 44, Bldg. 3.0, 8000 Aarhus C, DenmarkDepartment of Molecular MedicineAarhus University Hospital, Brendstrupgårdsvej 100, 8200 Aarhus N, Denmark.
authors.forename: Sten
authors.initials: S
authors.lastname: Lund
mesh_terms: D017667:Adipocytes / Q000378:metabolism*; D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D002395:Catecholamines; D004734:Energy Metabolism / Q000502:physiology; D005230:Fatty Acids, Nonesterified / Q000096:biosynthesis / Q000097:blood; D006801:Humans; D008049:Lipase / Q000378:metabolism*; D008066:Lipolysis / Q000502:physiology*; D008659:Metabolic Diseases; D051379:Mice; D008994:Monoacylglycerol Lipases / Q000378:metabolism; D009765:Obesity / Q000378:metabolism; D015398:Signal Transduction; D002787:Sterol Esterase / Q000378:metabolism*; D000217:Acyltransferases
chemical_list: D002395:Catecholamines; D005230:Fatty Acids, Nonesterified; D008049:Lipase; D008994:Monoacylglycerol Lipases; D002787:Sterol Esterase; C494794:PNPLA2 protein, human; D000217:Acyltransferases
keywords: ATGL; HSL; adipose tissue; free fatty acids; lipolysis; type 2 diabetes