Adipocyte ACLY Facilitates Dietary Carbohydrate Handling to Maintain Metabolic Homeostasis in Females
Name:
Publisher version
View Source
Access full-text PDFOpen Access
View Source
Check access options
Check access options
Authors
Fernandez, SullyViola, John M.
Torres, AnnMarie
Wallace, Martina
Trefely, Sophie
Zhao, Steven
Affronti, Hayley C.
Gengatharan, Jivani M.
Guertin, David A.
Snyder, Nathaniel W.
Metallo, Christian M.
Wellen, Kathryn E.
UMass Chan Affiliations
Program in Molecular MedicineDocument Type
Journal ArticlePublication Date
2019-05-28Keywords
ATP-citrate lyaseChREBP
acetyl-CoA
adipocyte
adipose tissue
carbohydrate
fatty acid synthesis
glucose
liver
sexual dimorphism
Amino Acids, Peptides, and Proteins
Biochemical Phenomena, Metabolism, and Nutrition
Biochemistry, Biophysics, and Structural Biology
Carbohydrates
Cell Biology
Cells
Cellular and Molecular Physiology
Enzymes and Coenzymes
Lipids
Metadata
Show full item recordAbstract
Sugars and refined carbohydrates are major components of the modern diet. ATP-citrate lyase (ACLY) is upregulated in adipocytes in response to carbohydrate consumption and generates acetyl-coenzyme A (CoA) for both lipid synthesis and acetylation reactions. Here, we investigate the role of ACLY in the metabolic and transcriptional responses to carbohydrates in adipocytes and unexpectedly uncover a sexually dimorphic function in maintaining systemic metabolic homeostasis. When fed a high-sucrose diet, Acly(FAT-/-) females exhibit a lipodystrophy-like phenotype, with minimal fat accumulation, insulin resistance, and hepatic lipid accumulation, whereas Acly(FAT-/-) males have only mild metabolic phenotypes. We find that ACLY is crucial for nutrient-dependent carbohydrate response element-binding protein (ChREBP) activation in adipocytes and plays a key role, particularly in females, in the storage of newly synthesized fatty acids in adipose tissue. The data indicate that adipocyte ACLY is important in females for the systemic handling of dietary carbohydrates and for the preservation of metabolic homeostasis.Source
Cell Rep. 2019 May 28;27(9):2772-2784.e6. doi: 10.1016/j.celrep.2019.04.112. Link to article on publisher's site
DOI
10.1016/j.celrep.2019.04.112Permanent Link to this Item
http://hdl.handle.net/20.500.14038/41051PubMed ID
31141698Related Resources
Rights
Copyright 2019 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).Distribution License
http://creativecommons.org/licenses/by-nc-nd/4.0/ae974a485f413a2113503eed53cd6c53
10.1016/j.celrep.2019.04.112
Scopus Count
Collections
Except where otherwise noted, this item's license is described as Copyright 2019 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).