Neurochemical and electrophysiological deficits in the ventral hippocampus and selective behavioral alterations caused by high-fat diet in female C57BL/6 mice

Time-dependent behavioral, neurochemical, and metabolic dysregulation in female C57BL/6 mice caused by chronic high-fat diet intake

“…It is noteworthy that majority of these reports are reflective of neurological manifestations at a single time point post HFD consumption and in the case of laboratory studies, most of the data are on males. To begin to fill the female-specific data void, in a recently published study we demonstrated that HFD intake by female C57BL/6 mice, even for a relatively short period (5–6 weeks), can cause emotional (anxiety-like) and locomotor (hyperactivity) deficits and associated neurochemical changes in specific regions (ventral hippocampus [vHIP]) of the brain [1]. However, excessive intake of dietary fat in humans is typically of a long-term, chronic nature.…”

“…In this paper, we aimed to (i) extend our previous work (on HFD-induced early central effects [1]) by looking at the concomitant peripheral effects (if any) following HFD consumption for a period of 5–6 weeks in female C57BL/6 mice and (ii) evaluate the time course of neurobehavioral/neurochemical and metabolic/inflammatory effects in female mice after long (20–22 weeks) and prolonged (32–36 weeks) HFD feeding. The extended feeding durations were selected based on data indicating that leptin signaling dysregulation, characterized by hyperleptinemia or leptin resistance, develops in male and female mice after 15–20 weeks on HFD [19–23] and that leptin status affects anxiety behavior and serotonin signaling [24].…”

“…Peripheral effects were evaluated at three feeding intervals (short: 5–6 weeks, long: 20–22 weeks, and prolonged: 33–36 weeks). Central effects were evaluated only after long and prolonged feeding durations; we have previously reported those effects after the short (5–6 weeks) feeding duration) [1]. Ongoing HFD feeding resulted in an obese phenotype characterized by increased visceral adiposity and, after prolonged HFD intake, an increase in liver and kidney weights.…”

How Metabolic State May Regulate Fear: Presence of Metabolic Receptors in the Fear Circuitry

“…In the context of a positive energy balance, the monoaminergic nuclei are most often reported to be involved in the elevation of fear. The dopaminergic reward circuitry is often implicated in obesity for the reinforcing effects of ‘palatable’ food and is known to influence fear (Wang et al, 2001; Volkow et al, 2012; Abraham et al, 2014; Krishna et al, 2015; Morris et al, 2015). Less is known about the involvement of the noradrenalin (NE) system, but altered NE metabolism in hippocampus and prefrontal cortex has been associated with fear behavior in diet-induced obese mice (Krishna et al, 2015).…”

“…The dopaminergic reward circuitry is often implicated in obesity for the reinforcing effects of ‘palatable’ food and is known to influence fear (Wang et al, 2001; Volkow et al, 2012; Abraham et al, 2014; Krishna et al, 2015; Morris et al, 2015). Less is known about the involvement of the noradrenalin (NE) system, but altered NE metabolism in hippocampus and prefrontal cortex has been associated with fear behavior in diet-induced obese mice (Krishna et al, 2015). Central serotonin (5-HT) signaling is most often reported as affected by obesity (Kimbrough and Weekley, 1984; Muldoon et al, 2006; Herrera-Marquez et al, 2011; Kurhe and Mahesh, 2015; Kurhe et al, 2015).…”