Maternal obesity disrupts circadian rhythms of clock and metabolic genes in the offspring heart and liver

Abstract

Early life nutritional adversity is tightly associated with the development of long-term metabolic disorders. Particularly, maternal obesity and high-fat diets cause high risk of obesity in the offspring. Those offspring are also prone to develop hyperinsulinemia, hepatic steatosis and cardiovascular diseases. However, the precise underlying mechanisms leading to these metabolic dysregulation in the offspring remain unclear. On the other hand, disruptions of diurnal circadian rhythms are known to impair metabolic homeostasis in various tissues including the heart and liver. Therefore, we investigated that whether maternal obesity perturbs the circadian expression rhythms of clock, metabolic and inflammatory genes in offspring heart and liver by using RT-qPCR and Western blotting analysis. Offspring from lean and obese dams were examined on postnatal day 17 and 35, when pups were nursed by their mothers or took food independently. On P17, genes examined in the heart either showed anti-phase oscillations (Cpt1b, Pparα, Per2) or had greater oscillation amplitudes (Bmal1, Tnf-α, Il-6). Such phase abnormalities of these genes were improved on P35, while defects in amplitudes still existed. In the liver of 17-day-old pups exposed to maternal obesity, the oscillation amplitudes of most rhythmic genes examined (except Bmal1) were strongly suppressed. On P35, the oscillations of circadian and inflammatory genes became more robust in the liver, while metabolic genes were still kept non-rhythmic. Maternal obesity also had a profound influence in the protein expression levels of examined genes in offspring heart and liver. Our observations indicate that the circadian clock undergoes nutritional programing, which may contribute to the alternations in energy metabolism associated with the development of metabolic disorders in early life and adulthood.

• Circadian clock
• maternal obesity
• metabolic programing
• offspring

DECLARATION OF INTEREST

The authors report no competing interests. The authors alone are responsible for the content and writing of the paper.

This work is supported by grants from the National Basic Research Program of China (973 Program) (2012CB947600, 2013CB911600), the National Natural Science Foundation of China (31422028, 31171137, 31271261, 31401009, 31171135), the Program for the Top Young Talents by the Organization Department of the CPC Central Committee, NSF of Jiangsu Province of China (BK20140041), the Collaborative Innovation Center for Cardiovascular Disease Translational Medicine (Nanjing Medical University) and the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).

Supplementary material available online

Supplementary Figures S1–S3 and Tables S1–S7