Diurnal variation in vascular and metabolic function in diet-induced obesity: divergence of insulin resistance and loss of clock rhythm.

Abstract:

:Circadian rhythms are integral to the normal functioning of numerous physiological processes. Evidence from human and mouse studies suggests that loss of rhythm occurs in obesity and cardiovascular disease and may be a neglected contributor to pathophysiology. Obesity has been shown to impair the circadian clock mechanism in liver and adipose tissue but its effect on cardiovascular tissues is unknown. We investigated the effect of diet-induced obesity in C57BL6J mice upon rhythmic transcription of clock genes and diurnal variation in vascular and metabolic systems. In obesity, clock gene function and physiological rhythms were preserved in the vasculature but clock gene transcription in metabolic tissues and rhythms of glucose tolerance and insulin sensitivity were blunted. The most pronounced attenuation of clock rhythm occurred in adipose tissue, where there was also impairment of clock-controlled master metabolic genes and both AMPK mRNA and protein. Across tissues, clock gene disruption was associated with local inflammation but diverged from impairment of insulin signaling. We conclude that vascular tissues are less sensitive to pathological disruption of diurnal rhythms during obesity than metabolic tissues and suggest that cellular disruption of clock gene rhythmicity may occur by mechanisms shared with inflammation but distinct from those leading to insulin resistance.

journal_name

Diabetes

journal_title

Diabetes

authors

Prasai MJ,Mughal RS,Wheatcroft SB,Kearney MT,Grant PJ,Scott EM

doi

10.2337/db11-1740

subject

Has Abstract

pub_date

2013-06-01 00:00:00

pages

1981-9

issue

6

eissn

0012-1797

issn

1939-327X

pii

db11-1740

journal_volume

62

pub_type

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