Program in Molecular Medicine
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
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.
ATP-citrate lyase, ChREBP, acetyl-CoA, adipocyte, adipose tissue, carbohydrate, fatty acid synthesis, glucose, liver, sexual dimorphism
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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/).
DOI of Published Version
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
Fernandez, Sully; Viola, 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.; and Wellen, Kathryn E., "Adipocyte ACLY Facilitates Dietary Carbohydrate Handling to Maintain Metabolic Homeostasis in Females" (2019). Open Access Articles. 3843.
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This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
Amino Acids, Peptides, and Proteins Commons, Biochemical Phenomena, Metabolism, and Nutrition Commons, Biochemistry, Biophysics, and Structural Biology Commons, Carbohydrates Commons, Cell Biology Commons, Cells Commons, Cellular and Molecular Physiology Commons, Enzymes and Coenzymes Commons, Lipids Commons