Rapid Alterations in Perirenal Adipose Tissue Transcriptomic Networks with Cessation of Voluntary Running

Abstract

In maturing rats, the growth of abdominal fat is attenuated by voluntary wheel running. After the cessation of running by wheel locking, a rapid increase in adipose tissue growth to a size that is similar to rats that have never run (i.e. catch-up growth) has been previously reported by our lab. In contrast, diet-induced increases in adiposity have a slower onset with relatively delayed transcriptomic responses. The purpose of the present study was to identify molecular pathways associated with the rapid increase in adipose tissue after ending 6 wks of voluntary running at the time of puberty. Age-matched, male Wistar rats were given access to running wheels from 4 to 10 weeks of age. From the 10th to 11th week of age, one group of rats had continued wheel access, while the other group had one week of wheel locking. Perirenal adipose tissue was extracted, RNA sequencing was performed, and bioinformatics analyses were executed using Ingenuity Pathway Analysis (IPA). IPA was chosen to assist in the understanding of complex ‘omics data by integrating data into networks and pathways. Wheel locked rats gained significantly more fat mass and significantly increased body fat percentage between weeks 10–11 despite having decreased food intake, as compared to rats with continued wheel access. IPA identified 646 known transcripts differentially expressed (p < 0.05) between continued wheel access and wheel locking. In wheel locked rats, IPA revealed enrichment of transcripts for the following functions: extracellular matrix, macrophage infiltration, immunity, and pro-inflammatory. These findings suggest that increases in visceral adipose tissue that accompanies the cessation of pubertal physical activity are associated with the alteration of multiple pathways, some of which may potentiate the development of pubertal obesity and obesity-associated systemic low-grade inflammation that occurs later in life.

Glucocorticoid antagonism limits adiposity rebound and glucose intolerance in young male rats following the cessation of daily exercise and caloric restriction

“…This suggests that the acute change in systemic inflammation did not contribute to the insulin resistance in the placebo post-WL group and that CRP levels are not tightly linked with 11␤-HSD1 expression in the epididymal fat pad. However, it was recently found that in wheel-locked rats there is an upregulation of gene transcripts related to immunity, macrophage infiltration, and proinflammation within perirenal adipose tissue (68). Thus, there may be local inflammatory changes in adipose tissue that play a key role in impaired metabolic health in the animals post-wheel lock.…”

“…Considering the link between adipose tissue inflammation, elevated 11␤-HSD1, and a recent study that demonstrated an upregulation of adipose proinflammatory gene transcripts following wheel lock in rats (68), future studies should explore whether a key protective mechanism of mifepristone is through reducing local inflammatory markers such as TNF␣, IL-6, and NF-B or by limiting macrophage infiltration. Conversely, it would be interesting to determine whether administration of an anti-inflammatory compound would yield similar metabolic benefits following wheel lock.…”

5‐Aminoimidazole‐4‐carboxamide ribonucleotide prevents fat gain following the cessation of voluntary physical activity

“…; Ruegsegger et al . ), to levels comparable to those of rats with continuous wheel access. Additionally, we assessed mRNA expression in omental (OMAT) and subcutaneous adipose tissue (SAT) associated with hypoxia ( Vegf , Hif1α ), cell proliferation and differentiation ( Cdk2 , cyclin A1, cyclin D1) and metabolism (adiponectin, leptin), as well as energy homeostasis‐regulating mRNAs in the hypothalamus ( Pomc , Cart , Agrp , Npy , Lepr ).…”

“…; Ruegsegger et al . ), highlighting the importance of energy expenditure on adipocyte expansion during endurance types of exercise. Consistent with lack of change in food intake, we did not find differences in appetite control mRNAs in the Arc.…”

“…Western blotting was performed on OMAT and SAT samples as previously described (Ruegsegger et al . ). Equal loading was verified by Ponceau S (Sigma).…”