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Journal article
Adipocyte ACLY Facilitates Dietary Carbohydrate Handling to Maintain Metabolic Homeostasis in Females
Cell reports (Cambridge), v 27(9), pp 2772-2784
28 May 2019
PMID: 31141698
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
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, AclyFAT−/− females exhibit a lipodystrophy-like phenotype, with minimal fat accumulation, insulin resistance, and hepatic lipid accumulation, whereas AclyFAT−/− 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.
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•ACLY promotes glucose-induced ChREBP activation in white adipocytes•Sex impacts the ACLY-dependent storage of lipids in adipose tissue•Adipocyte ACLY deficiency results in insulin resistance in females•Female dependence on adipocyte ACLY is enhanced with a high-glycemic-index diet
Sugar is a major component of the modern diet. Fernandez et al. identify ATP-citrate lyase (ACLY) as a key facilitator of transcriptional and metabolic responses to dietary carbohydrates in adipocytes. Lack of adipocyte ACLY disrupts proper storage of lipids in adipose versus liver and promotes insulin resistance, particularly in females.
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- Title
- Adipocyte ACLY Facilitates Dietary Carbohydrate Handling to Maintain Metabolic Homeostasis in Females
- Creators
- Sully Fernandez - Department of Cancer Biology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Abramson Family Cancer Research Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.John M. Viola - University of PennsylvaniaAnnMarie Torres - Department of Cancer Biology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USAMartina Wallace - University of California, San DiegoSophie Trefely - Drexel UniversitySteven Zhao - University of PennsylvaniaHayley C. Affronti - University of PennsylvaniaJivani M. Gengatharan - University of California, San DiegoDavid A. Guertin - University of Massachusetts Medical SchoolNathaniel W. Snyder - Drexel UniversityChristian M. Metallo - University of California, San DiegoKathryn E. Wellen - University of Pennsylvania
- Publication Details
- Cell reports (Cambridge), v 27(9), pp 2772-2784
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- A.J. Drexel Autism Institute
- Web of Science ID
- WOS:000469216500021
- Scopus ID
- 2-s2.0-85065803532
- Other Identifier
- 991019168115104721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Cell Biology