Adipocyte ACLY Facilitates Dietary Carbohydrate Handling to Maintain Metabolic Homeostasis in Females
Viola, John M.
Affronti, Hayley C.
Gengatharan, Jivani M.
Guertin, David A.
Snyder, Nathaniel W.
Metallo, Christian M.
Wellen, Kathryn E.
UMass Chan AffiliationsProgram in Molecular Medicine
Document TypeJournal Article
fatty acid synthesis
Amino Acids, Peptides, and Proteins
Biochemical Phenomena, Metabolism, and Nutrition
Biochemistry, Biophysics, and Structural Biology
Cellular and Molecular Physiology
Enzymes and Coenzymes
MetadataShow full item record
AbstractSugars 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.
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
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/41051
RightsCopyright 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/).
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/).