Circadian signatures of adipose tissue in diet-induced obesity

High-fat diet (HFD) feeding rewires circadian rhythms of peripheral organs including the liver and adipose tissue. While the liver has been extensively studied, it remains largely unknown whether and how HFD organizes circadian biology in adipose tissue. Here, we took a systems approach to profile t...

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Main Authors: Haoran Xin, Jianxin Zhang, Rongfeng Huang, Lihua Li, Sin Man Lam, Guanghou Shui, Fang Deng, Zhihui Zhang, Min-Dian Li
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-08-01
Series:Frontiers in Physiology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fphys.2022.953237/full
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author Haoran Xin
Jianxin Zhang
Rongfeng Huang
Lihua Li
Sin Man Lam
Sin Man Lam
Guanghou Shui
Fang Deng
Zhihui Zhang
Min-Dian Li
author_facet Haoran Xin
Jianxin Zhang
Rongfeng Huang
Lihua Li
Sin Man Lam
Sin Man Lam
Guanghou Shui
Fang Deng
Zhihui Zhang
Min-Dian Li
author_sort Haoran Xin
collection DOAJ
description High-fat diet (HFD) feeding rewires circadian rhythms of peripheral organs including the liver and adipose tissue. While the liver has been extensively studied, it remains largely unknown whether and how HFD organizes circadian biology in adipose tissue. Here, we took a systems approach to profile the diurnal transcriptome of adipose tissue in diet-induced obese mice either fed a low-fat diet (LFD) that reduces weight or still fed HFD. We detected about 200 and 2,500 diurnal genes in HFD and LFD, respectively. Pathway analysis revealed that rhythmic pathways in HFD are represented by circadian rhythm, ribosome biogenesis, and nucleosome organization, whereas those in LFD are represented by myeloid cell function. Remarkably, the majority of the circadian clock genes, except Clock, exhibited robust diurnal rhythm in the adipose tissue of HFD-fed mice. Analysis of mRNAs and proteins in another cohort of HFD-fed mice confirmed that Clock lost rhythmicity at the transcript, but not protein level. Diet reversal to LFD specifically restored diurnal difference of the Clock transcripts in adipose tissue. We matched transcriptomics data with global profiling of neutral lipids and found that lipid metabolism catalyzed by triglycerol hydrolase Ces1d is a key circadian feature that is activated by diet reversal. Together, our work defines the circadian signatures in the adipose tissue of diet-induced obese mice, and their flexibility upon dietary intervention, thereby shedding light on potential clock-modulated tissue-specific pathways during obesity.
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spelling doaj.art-da4958669dec426890218b4728c6a1142022-12-22T04:19:02ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2022-08-011310.3389/fphys.2022.953237953237Circadian signatures of adipose tissue in diet-induced obesityHaoran Xin0Jianxin Zhang1Rongfeng Huang2Lihua Li3Sin Man Lam4Sin Man Lam5Guanghou Shui6Fang Deng7Zhihui Zhang8Min-Dian Li9Department of Cardiovascular Medicine, Center for Circadian Metabolism and Cardiovascular Disease, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, ChinaDepartment of Cardiovascular Medicine, Center for Circadian Metabolism and Cardiovascular Disease, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, ChinaDepartment of Cardiovascular Medicine, Center for Circadian Metabolism and Cardiovascular Disease, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, ChinaDepartment of Cardiovascular Medicine, Center for Circadian Metabolism and Cardiovascular Disease, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, ChinaState Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, ChinaLipidall Technologies Company Limited, Changzhou, ChinaState Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, ChinaDepartment of Pathophysiology, College of High Altitude Military Medicine, Army Medical University (Third Military Medical University), Chongqing, ChinaDepartment of Cardiovascular Medicine, Center for Circadian Metabolism and Cardiovascular Disease, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, ChinaDepartment of Cardiovascular Medicine, Center for Circadian Metabolism and Cardiovascular Disease, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, ChinaHigh-fat diet (HFD) feeding rewires circadian rhythms of peripheral organs including the liver and adipose tissue. While the liver has been extensively studied, it remains largely unknown whether and how HFD organizes circadian biology in adipose tissue. Here, we took a systems approach to profile the diurnal transcriptome of adipose tissue in diet-induced obese mice either fed a low-fat diet (LFD) that reduces weight or still fed HFD. We detected about 200 and 2,500 diurnal genes in HFD and LFD, respectively. Pathway analysis revealed that rhythmic pathways in HFD are represented by circadian rhythm, ribosome biogenesis, and nucleosome organization, whereas those in LFD are represented by myeloid cell function. Remarkably, the majority of the circadian clock genes, except Clock, exhibited robust diurnal rhythm in the adipose tissue of HFD-fed mice. Analysis of mRNAs and proteins in another cohort of HFD-fed mice confirmed that Clock lost rhythmicity at the transcript, but not protein level. Diet reversal to LFD specifically restored diurnal difference of the Clock transcripts in adipose tissue. We matched transcriptomics data with global profiling of neutral lipids and found that lipid metabolism catalyzed by triglycerol hydrolase Ces1d is a key circadian feature that is activated by diet reversal. Together, our work defines the circadian signatures in the adipose tissue of diet-induced obese mice, and their flexibility upon dietary intervention, thereby shedding light on potential clock-modulated tissue-specific pathways during obesity.https://www.frontiersin.org/articles/10.3389/fphys.2022.953237/fullcircadian clockhigh-fat dietadipose tissuetranscriptomicsCLOCKCES1D
spellingShingle Haoran Xin
Jianxin Zhang
Rongfeng Huang
Lihua Li
Sin Man Lam
Sin Man Lam
Guanghou Shui
Fang Deng
Zhihui Zhang
Min-Dian Li
Circadian signatures of adipose tissue in diet-induced obesity
Frontiers in Physiology
circadian clock
high-fat diet
adipose tissue
transcriptomics
CLOCK
CES1D
title Circadian signatures of adipose tissue in diet-induced obesity
title_full Circadian signatures of adipose tissue in diet-induced obesity
title_fullStr Circadian signatures of adipose tissue in diet-induced obesity
title_full_unstemmed Circadian signatures of adipose tissue in diet-induced obesity
title_short Circadian signatures of adipose tissue in diet-induced obesity
title_sort circadian signatures of adipose tissue in diet induced obesity
topic circadian clock
high-fat diet
adipose tissue
transcriptomics
CLOCK
CES1D
url https://www.frontiersin.org/articles/10.3389/fphys.2022.953237/full
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