Chronic environmental circadian disruption increases atherosclerosis and dyslipidemia in female, but not male, ApolipoproteinE-deficient mice

Shift work chronically disrupts circadian rhythms and increases the risk of developing cardiovascular disease. However, the mechanisms linking shift work and cardiovascular disease are largely unknown. The goal of this study was to investigate the effects of chronically shifting the light-dark (LD)...

Full description

Bibliographic Details
Main Authors: Jeffrey M. Chalfant, Deborah A. Howatt, Victoria B. Johnson, Lisa R. Tannock, Alan Daugherty, Julie S. Pendergast
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-03-01
Series:Frontiers in Physiology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fphys.2023.1167858/full
_version_ 1827977312651444224
author Jeffrey M. Chalfant
Jeffrey M. Chalfant
Deborah A. Howatt
Victoria B. Johnson
Lisa R. Tannock
Lisa R. Tannock
Lisa R. Tannock
Lisa R. Tannock
Alan Daugherty
Alan Daugherty
Julie S. Pendergast
Julie S. Pendergast
Julie S. Pendergast
author_facet Jeffrey M. Chalfant
Jeffrey M. Chalfant
Deborah A. Howatt
Victoria B. Johnson
Lisa R. Tannock
Lisa R. Tannock
Lisa R. Tannock
Lisa R. Tannock
Alan Daugherty
Alan Daugherty
Julie S. Pendergast
Julie S. Pendergast
Julie S. Pendergast
author_sort Jeffrey M. Chalfant
collection DOAJ
description Shift work chronically disrupts circadian rhythms and increases the risk of developing cardiovascular disease. However, the mechanisms linking shift work and cardiovascular disease are largely unknown. The goal of this study was to investigate the effects of chronically shifting the light-dark (LD) cycle, which models the disordered exposure to light that may occur during shift work, on atherosclerosis. Atherosclerosis is the progressive accumulation of lipid-filled lesions within the artery wall and is the leading cause of cardiovascular disease. We studied ApolipoproteinE-deficient (ApoE−/−) mice that are a well-established model of atherosclerosis. Male and female ApoE−/− mice were housed in control 12L:12D or chronic LD shift conditions for 12 weeks and fed low-fat diet. In the chronic LD shift condition, the light-dark cycle was advanced by 6 h every week. We found that chronic LD shifts exacerbated atherosclerosis in female, but not male, ApoE−/− mice. In females, chronic LD shifts increased total serum cholesterol concentrations with increased atherogenic VLDL/LDL particles. Chronic LD shifts did not affect food intake, activity, or body weight in male or female ApoE−/− mice. We also examined eating behavior in female ApoE−/− mice since aberrant meal timing has been linked to atherosclerosis. The phases of eating behavior rhythms, like locomotor activity rhythms, gradually shifted to the new LD cycle each week in the chronic LD shift group, but there was no effect of the LD shift on the amplitudes of the eating rhythms. Moreover, the duration of fasting intervals was not different in control 12L:12D compared to chronic LD shift conditions. Together these data demonstrate that female ApoE−/− mice have increased atherosclerosis when exposed to chronic LD shifts due to increased VLDL/LDL cholesterol, independent of changes in energy balance or feeding-fasting cycles.
first_indexed 2024-04-09T21:03:59Z
format Article
id doaj.art-55fd1e4ec5f342b6ae656ed535681aca
institution Directory Open Access Journal
issn 1664-042X
language English
last_indexed 2024-04-09T21:03:59Z
publishDate 2023-03-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Physiology
spelling doaj.art-55fd1e4ec5f342b6ae656ed535681aca2023-03-29T05:05:09ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2023-03-011410.3389/fphys.2023.11678581167858Chronic environmental circadian disruption increases atherosclerosis and dyslipidemia in female, but not male, ApolipoproteinE-deficient miceJeffrey M. Chalfant0Jeffrey M. Chalfant1Deborah A. Howatt2Victoria B. Johnson3Lisa R. Tannock4Lisa R. Tannock5Lisa R. Tannock6Lisa R. Tannock7Alan Daugherty8Alan Daugherty9Julie S. Pendergast10Julie S. Pendergast11Julie S. Pendergast12Department of Biology, University of Kentucky, Lexington, KY, United StatesSaha Cardiovascular Research Center, University of Kentucky, Lexington, KY, United StatesSaha Cardiovascular Research Center, University of Kentucky, Lexington, KY, United StatesDepartment of Biology, University of Kentucky, Lexington, KY, United StatesSaha Cardiovascular Research Center, University of Kentucky, Lexington, KY, United StatesDepartment of Veterans Affairs, Lexington, KY, United StatesDepartment of Internal Medicine, University of Kentucky, Lexington, KY, United StatesBarnstable Brown Diabetes Center, University of Kentucky, Lexington, KY, United StatesSaha Cardiovascular Research Center, University of Kentucky, Lexington, KY, United StatesDepartment of Physiology, University of Kentucky, Lexington, KY, United StatesDepartment of Biology, University of Kentucky, Lexington, KY, United StatesSaha Cardiovascular Research Center, University of Kentucky, Lexington, KY, United StatesBarnstable Brown Diabetes Center, University of Kentucky, Lexington, KY, United StatesShift work chronically disrupts circadian rhythms and increases the risk of developing cardiovascular disease. However, the mechanisms linking shift work and cardiovascular disease are largely unknown. The goal of this study was to investigate the effects of chronically shifting the light-dark (LD) cycle, which models the disordered exposure to light that may occur during shift work, on atherosclerosis. Atherosclerosis is the progressive accumulation of lipid-filled lesions within the artery wall and is the leading cause of cardiovascular disease. We studied ApolipoproteinE-deficient (ApoE−/−) mice that are a well-established model of atherosclerosis. Male and female ApoE−/− mice were housed in control 12L:12D or chronic LD shift conditions for 12 weeks and fed low-fat diet. In the chronic LD shift condition, the light-dark cycle was advanced by 6 h every week. We found that chronic LD shifts exacerbated atherosclerosis in female, but not male, ApoE−/− mice. In females, chronic LD shifts increased total serum cholesterol concentrations with increased atherogenic VLDL/LDL particles. Chronic LD shifts did not affect food intake, activity, or body weight in male or female ApoE−/− mice. We also examined eating behavior in female ApoE−/− mice since aberrant meal timing has been linked to atherosclerosis. The phases of eating behavior rhythms, like locomotor activity rhythms, gradually shifted to the new LD cycle each week in the chronic LD shift group, but there was no effect of the LD shift on the amplitudes of the eating rhythms. Moreover, the duration of fasting intervals was not different in control 12L:12D compared to chronic LD shift conditions. Together these data demonstrate that female ApoE−/− mice have increased atherosclerosis when exposed to chronic LD shifts due to increased VLDL/LDL cholesterol, independent of changes in energy balance or feeding-fasting cycles.https://www.frontiersin.org/articles/10.3389/fphys.2023.1167858/fullcircadian rhythmshift workcardiovascular diseaseeating rhythmfasting
spellingShingle Jeffrey M. Chalfant
Jeffrey M. Chalfant
Deborah A. Howatt
Victoria B. Johnson
Lisa R. Tannock
Lisa R. Tannock
Lisa R. Tannock
Lisa R. Tannock
Alan Daugherty
Alan Daugherty
Julie S. Pendergast
Julie S. Pendergast
Julie S. Pendergast
Chronic environmental circadian disruption increases atherosclerosis and dyslipidemia in female, but not male, ApolipoproteinE-deficient mice
Frontiers in Physiology
circadian rhythm
shift work
cardiovascular disease
eating rhythm
fasting
title Chronic environmental circadian disruption increases atherosclerosis and dyslipidemia in female, but not male, ApolipoproteinE-deficient mice
title_full Chronic environmental circadian disruption increases atherosclerosis and dyslipidemia in female, but not male, ApolipoproteinE-deficient mice
title_fullStr Chronic environmental circadian disruption increases atherosclerosis and dyslipidemia in female, but not male, ApolipoproteinE-deficient mice
title_full_unstemmed Chronic environmental circadian disruption increases atherosclerosis and dyslipidemia in female, but not male, ApolipoproteinE-deficient mice
title_short Chronic environmental circadian disruption increases atherosclerosis and dyslipidemia in female, but not male, ApolipoproteinE-deficient mice
title_sort chronic environmental circadian disruption increases atherosclerosis and dyslipidemia in female but not male apolipoproteine deficient mice
topic circadian rhythm
shift work
cardiovascular disease
eating rhythm
fasting
url https://www.frontiersin.org/articles/10.3389/fphys.2023.1167858/full
work_keys_str_mv AT jeffreymchalfant chronicenvironmentalcircadiandisruptionincreasesatherosclerosisanddyslipidemiainfemalebutnotmaleapolipoproteinedeficientmice
AT jeffreymchalfant chronicenvironmentalcircadiandisruptionincreasesatherosclerosisanddyslipidemiainfemalebutnotmaleapolipoproteinedeficientmice
AT deborahahowatt chronicenvironmentalcircadiandisruptionincreasesatherosclerosisanddyslipidemiainfemalebutnotmaleapolipoproteinedeficientmice
AT victoriabjohnson chronicenvironmentalcircadiandisruptionincreasesatherosclerosisanddyslipidemiainfemalebutnotmaleapolipoproteinedeficientmice
AT lisartannock chronicenvironmentalcircadiandisruptionincreasesatherosclerosisanddyslipidemiainfemalebutnotmaleapolipoproteinedeficientmice
AT lisartannock chronicenvironmentalcircadiandisruptionincreasesatherosclerosisanddyslipidemiainfemalebutnotmaleapolipoproteinedeficientmice
AT lisartannock chronicenvironmentalcircadiandisruptionincreasesatherosclerosisanddyslipidemiainfemalebutnotmaleapolipoproteinedeficientmice
AT lisartannock chronicenvironmentalcircadiandisruptionincreasesatherosclerosisanddyslipidemiainfemalebutnotmaleapolipoproteinedeficientmice
AT alandaugherty chronicenvironmentalcircadiandisruptionincreasesatherosclerosisanddyslipidemiainfemalebutnotmaleapolipoproteinedeficientmice
AT alandaugherty chronicenvironmentalcircadiandisruptionincreasesatherosclerosisanddyslipidemiainfemalebutnotmaleapolipoproteinedeficientmice
AT juliespendergast chronicenvironmentalcircadiandisruptionincreasesatherosclerosisanddyslipidemiainfemalebutnotmaleapolipoproteinedeficientmice
AT juliespendergast chronicenvironmentalcircadiandisruptionincreasesatherosclerosisanddyslipidemiainfemalebutnotmaleapolipoproteinedeficientmice
AT juliespendergast chronicenvironmentalcircadiandisruptionincreasesatherosclerosisanddyslipidemiainfemalebutnotmaleapolipoproteinedeficientmice