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Circadian mutant mice with obesity and metabolic syndrome are resilient to cardiovascular disease

American journal of physiology. Heart and circulatory physiology, 2020-11, Vol.319 (5), p.H1097-H1111 [Peer Reviewed Journal]

Copyright American Physiological Society Nov 2020 ;ISSN: 0363-6135 ;EISSN: 1522-1539 ;DOI: 10.1152/AJPHEART.00462.2020 ;PMID: 32986958

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Title:
Circadian mutant mice with obesity and metabolic syndrome are resilient to cardiovascular disease
Author: Reitz, Cristine J ; Alibhai, Faisal J ; de Lima-Seolin, Bruna Gazzi ; Nemec-Bakk, Ashley ; Khaper, Neelam ; Martino, Tami A
Subjects: 4-Hydroxynonenal ; Animals ; Antioxidants ; Bioinformatics ; Cardiomyocytes ; Cardiovascular disease ; Cardiovascular diseases ; Cardiovascular Diseases - etiology ; Cardiovascular Diseases - genetics ; Cardiovascular Diseases - metabolism ; Catalase ; Catalase - metabolism ; Circadian rhythm ; Circadian rhythms ; CLOCK Proteins - genetics ; Diet ; DNA microarrays ; Gene expression ; Glutathione ; Glutathione peroxidase ; Glutathione Peroxidase - metabolism ; High fat diet ; Hypertrophy ; Male ; Metabolic disorders ; Metabolic syndrome ; Metabolic Syndrome - complications ; Metabolic Syndrome - genetics ; Metabolic Syndrome - metabolism ; Mice ; Mice, Inbred C57BL ; Mutation ; Myocardium - metabolism ; Obesity ; Obesity - complications ; Obesity - genetics ; Obesity - metabolism ; Oxidative Stress ; Pathways ; Peroxidase ; PPAR gamma - metabolism ; Reactive oxygen species ; Resilience ; Sirtuins - metabolism ; Structure-function relationships ; Transcription
Is Part Of: American journal of physiology. Heart and circulatory physiology, 2020-11, Vol.319 (5), p.H1097-H1111
Description: Obesity and metabolic syndrome commonly underlie cardiovascular disease. mice fed a normal diet develop obesity and metabolic syndrome; however, it is not known whether they develop or are resilient to cardiovascular disease. We found that mice do not develop cardiac dysfunction, despite their underlying conditions. Moreover, in contrast to wild-type controls fed a high-fat diet (HFD), HFD mice still do not develop cardiovascular disease. Indeed, HFD mice have preserved heart weight despite their obesity, no cardiomyocyte hypertrophy, and preserved heart structure and function, even after 24 wk of a HFD. To determine why mice are resilient to cardiac dysfunction despite their underlying obesity and metabolic conditions, we examined global cardiac gene expression profiles by microarray and bioinformatics analyses, revealing that oxidative stress pathways were involved. We examined the pathways in further detail and found that ) SIRT-dependent oxidative stress pathways were not directly involved in resilience; ) 4-hydroxynonenal (4-HNE) increased in wild-type HFD but not mice, suggesting less reactive oxygen species in mice; ) cardiac catalase (CAT) and glutathione peroxidase (GPx) increased, suggesting strong antioxidant defenses in the hearts of mice; and ) was upregulated in the hearts of mice; this circadian-regulated gene drives transcription of CAT and GPx, providing a molecular basis for resilience in the mice. These findings shed new light on the circadian regulation of oxidative stress and demonstrate an important role for the circadian mechanism in resilience to cardiovascular disease. We examined whether obesity and metabolic syndrome underlie the development of cardiac dysfunction in circadian mutant mice. Surprisingly, we demonstrate that although mice develop metabolic dysfunction, they are protected from cardiac hypertrophy, left ventricular remodeling, and diastolic dysfunction, in contrast to wild-type controls, even when challenged with a chronic high-fat diet. These findings shed new light on the circadian regulation of oxidative stress pathways, which can mediate resilience to cardiovascular disease.
Publisher: United States: American Physiological Society
Language: English
Identifier: ISSN: 0363-6135
EISSN: 1522-1539
DOI: 10.1152/AJPHEART.00462.2020
PMID: 32986958
Source: GFMER Free Medical Journals
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Circadian mutant mice with obesity and metabolic syndrome are resilient to cardiovascular disease

Copyright American Physiological Society Nov 2020 ;ISSN: 0363-6135 ;EISSN: 1522-1539 ;DOI: 10.1152/AJPHEART.00462.2020 ;PMID: 32986958

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