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Adipocyte ACLY Facilitates Dietary Carbohydrate Handling to Maintain Metabolic Homeostasis in Females.
- Source :
-
Cell reports [Cell Rep] 2019 May 28; Vol. 27 (9), pp. 2772-2784.e6. - Publication Year :
- 2019
-
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, Acly <superscript>FAT-/-</superscript> females exhibit a lipodystrophy-like phenotype, with minimal fat accumulation, insulin resistance, and hepatic lipid accumulation, whereas Acly <superscript>FAT-/-</superscript> 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.<br /> (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Acetylation
Adipocytes cytology
Adult
Animals
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors metabolism
Female
Humans
Male
Mice
Mice, Knockout
Middle Aged
ATP Citrate (pro-S)-Lyase physiology
Adipocytes metabolism
Dietary Carbohydrates administration & dosage
Fatty Acids metabolism
Homeostasis
Insulin Resistance
Lipogenesis
Subjects
Details
- Language :
- English
- ISSN :
- 2211-1247
- Volume :
- 27
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Cell reports
- Publication Type :
- Academic Journal
- Accession number :
- 31141698
- Full Text :
- https://doi.org/10.1016/j.celrep.2019.04.112