Topical Area: Diet and Cancer
Circadian rhythms control daily functions (e.g. eating and sleeping patterns) and maintain metabolic homeostasis. Circadian disruption (e.g. erratic eating behavior) may increase the risk of obesity and breast cancer. Recent studies show that obesity causes circadian disruption in multiple organs. Girls with higher BMIs are likely to experience puberty at an earlier age. However, the impact of obesity on circadian signaling in breast tissue is unexplored. We hypothesized that consumption of a high-fat diet (HFD) disrupts circadian rhythmicity which leads to aberrant mammary gland development. The objective of this study was to determine the effect of high-fat diet on circadian rhythmicity in mammary gland development during the pre-pubertal stage in female mice.
Weanling female C57BL/6 mice, housed under a 12:12-hr light/dark cycle, were fed the AIN93G diet or a HFD (16 percent or 45 percent of energy from soybean oil) for 3 wks. Mice were euthanized every 4 hrs over a 48 hr period on Zeitgeber time at 6 wks of age (pre-puberty) and mammary glands were collected. The mRNA expression of clock genes and components of the steroid hormone system in mammary glands were analyzed at each time point. Differences in amplitude and phase shift (acrophase) between the two groups were compared by using the Cosinor analysis by SAS.
Compared to the AIN93G diet, the HFD increased the amplitude of expression of Clock, Rev-erb alpha, and Per1 by 97 percent, 55 percent, and 53 percent and decreased that of Per2, Cry1, and estrogen-receptor (ER) beta by 50 percent, 33 percent, and 35 percent, respectively. There were no significant amplitude differences in the expression of BMAL1, ER alpha, and progesterone receptor (PR) between the two groups. The HFD delayed the expression of Bmal1 and PR by 2.2 and 2.8 hrs, respectively, and resulted in a 1.8 hrs phase advance in Per2 expression compared to the AIN93G diet. There were no significant phase shifts in the expression of Clock, Rev-erb alpha, Per1, Cry1, ER alpha, and ER beta between the two groups.
Eating the HFD resulted in amplitude and phase changes in rhythmic expression of core-clock genes as well as steroid receptor hormones. These changes may lead to pathophysiologic changes in mammary gland that contribute to later development of breast cancer.
Funding Sources : USDA ARS 3062-51000-050-00D