Rebound Feeding in the Wake of Short-Term Suspension of Food Intake Differs in the Presence of Estrous Cycle Peak versus Nadir Levels of Estradiol

Abstract

BackgroundShort-term interruption of feeding is ordinary in modern life but negatively impacts appetite control and body weight. Estradiol (E) imposes long-term inhibitory tonus on food consumption; however, E influence on energy repletion secondary to food deprivation (FD) is unclear. This study investigated the hypothesis that E signal strength regulates hyperphagic responses to FD of varying duration.MethodsOvariectomized female rats were implanted with E-containing silastic capsules (30 [E-30] or 300 µg [E-300]/mL) to replicate plasma concentrations at cycle nadir versus peak levels.ResultsData show that food intake was increased equally in E-30 and E-300 rats after 12 hours of food deprivation (FD-12); yet, FD of 18 hours (FD-18) amplified refeeding by E-300 versus E-30. Caudal fourth ventricular administration of the 5′-monophosphate-activated protein kinase (AMPK) inhibitor compound C (Cc) did not modify FD-induced hyperphagia in E-30 (regardless of FD interval) or E-300 animals exposed to FD-12, but diminished refeeding after FD-18 in E-300 rats. Cc-reversible hyperglycemia occurred in refed FD-18 groups. Serum insulin was resistant to FD-12 plus refeeding, but was elevated by AMPK-dependent mechanisms in refed E-300 FD-18 rats; equivalent Cc-insensitive decrements in circulating leptin occurred in all FD groups.ConclusionCurrent results show that estrous cycle peak, but not baseline, E levels engage hindbrain AMPK signaling to intensify hyperphagia in response to prolongation of FD. Observations of hindbrain AMPK-dependent hyperglycemia, alongside elevated insulin secretion, in refed rats exposed to FD-18 implicate this sensor in insulin resistance mechanisms of glucose partitioning in response to this metabolic imbalance.

Assessing the effects of stress on feeding behaviors in laboratory mice

“…Daily food intake fluctuates across the estrous cycle, with reductions during proestrus, when estrogen is at its peak, in rodents and humans ( Tarttelin and Gorski, 1971 ; Petersen, 1976 ; Buffenstein et al, 1995 ). In contrast, fasting-induced food intake was significantly higher in proestrus than in diestrus, consistent with studies involving estrogen replacement in ovariectomy ( Shakya and Briski, 2017 ). Low home cage intake after an overnight fast in diestrus likely reflects increased stress, because it is restored by automated measurements.…”

A Framework for Developing Translationally Relevant Animal Models of Stress-Induced Changes in Eating Behavior

“…Yet, studies that explicitly examined stress-induced feeding behaviors in female rodents across the estrous cycle do not support the idea that these fluctuations are a major source of variability (41,(58)(59)(60). However, there are some contexts when differences in the levels of gonadal hormones exert a strong effect on food intake, such as a severe fast (61) or adolescent stress (62).…”

“…Recommendation: Considering that levels of gonadal hormones can affect the outcome of the assay in some contexts (61,62), differences across the estrous cycle should first be assessed.…”