High-Fat Diet-Induced Weight Gain, Behavioral Deficits, and Dopamine Changes in Young C57BL/6J Mice

Abstract

Chronic exposure to a high-fat diet (HFD) may predispose individuals to neuropathologies and behavioral deficits. The objective of this study was to determine the temporal effects of a HFD on weight gain, behavioral deficits, and dopamine changes in young mice. One-month old C57BL/6J male and female mice were fed either a control diet (containing 10% calories from fat) or a HFD (containing 45% of calories from fat) for 5 months. Physiological measures such as food consumption, body weight, blood glucose, and behaviors such as motor activity, sensorimotor integration, and anxiety-like behaviors were evaluated monthly. Dopamine (DA), dopamine receptor D2 (DRD2), and dopamine transporter (DT) protein expression levels were measured in the midbrain after 5 months of dietary exposure. Results showed that body weight was significantly greater in the HFD-exposed group compared to the control-group at the end of the 4th month, while food consumption was similar in both groups. For behavioral effects, the HFD group exhibited a significant decrease in motor activity in the open field test after 3 months, and rearing frequency after 4 months of dietary exposure. The HFD group also showed deficits in sensorimotor integration after 3 months. Specifically, chronic HFD exposure increased contact time and time to remove the first adhesive tape in the adhesive-tape removal test (p < 0.05). Furthermore, the HFD group showed significant deficits in balance/coordination compared to the control group after 4 months of dietary exposure using the beam traverse test, and increased anxiety-like behavior tested by both the open field and light/dark box tests (p < 0.05). Neurochemical measurements showed that HFD-exposed mice had significantly higher midbrain DA and DRD2 protein levels compared to the control group after 5 months of dietary exposure (p < 0.05). These results indicate that the impact of HFD on the C57BL/6J mouse strain began at the 3rd month of dietary exposure. Behavioral deficits occurred at a similar time point as increased body weight, at about 3–4 months. Overall, this study provides a critical understanding on how HFD-induced changes in weight gain and behavioral deficits in this strain occur over time. The behavioral changes support the idea that changes also occurred in neurochemical pathways such as dopamine dysregulation.

The majority of brain palmitic acid is maintained by lipogenesis from dietary sugars and is augmented in mice fed low palmitic acid levels from birth

“…This confirms any differences observed are because of diet treatment and not skewed by inactivity (Seibenhener & Wooten, 2015). Thigmotaxic-responses, including the tendency to remain close to vertical surfaces, particularly corners, is a well-established indicator of anxiety-like behavior in the Open Field test that has been validated in animal models with anxiogenic (Simon et al, 1994) and anxiolytic drugs (Simon et al, 1994;Treit & Fundytus, 1988) Field test specifically (Almeida-Suhett et al, 2019;Deal et al, 2020;Dutheil et al, 2016;Haleem & Mahmood, 2021;Han et al, 2021;Hryhorczuk et al, 2017;Keleher et al, 2018;Krishna et al, 2015;Noronha et al, 2019;Sivanathan et al, 2015;Zemdegs et al, 2016).…”

“…Several studies have investigated the impact of a high‐fat diet (35–60% energy from fat), compared to a control diet or diet lower in fat (3–17% energy from fat) on measures of anxiety using the Open Field test specifically (Almeida‐Suhett et al, 2019; Deal et al, 2020; Dutheil et al, 2016; Haleem & Mahmood, 2021; Han et al, 2021; Hryhorczuk et al, 2017; Keleher et al, 2018; Krishna et al, 2015; Noronha et al, 2019; Sivanathan et al, 2015; Zemdegs et al, 2016). However, studies investigating the relationship between anxiety‐like behavior and dietary PAM alone are scarce.…”

Effect of Dietary Grapes on Female C57BL6/J Mice Consuming a High-Fat Diet: Behavioral and Genetic Changes

“…In a study that was reported by Cagniard et al [ 32 ] with mice, it was found that a chronic increase of dopamine levels correlates with increased binge eating behavior and limited learning abilities. In addition, mice with increased dopamine receptor 2 activity exhibited reduced exploratory behavior and impaired locomotor activity [ 33 , 34 ].…”

Exploring the link between Parkinson's disease and type 2 diabetes mellitus in Drosophila

“…Similar results have been obtained in other T2DM mouse models. 20,55,56 To date, the cause by which T2DM might be triggering PD development remains unclear. The potential causes described are vascular defects, increased levels of methylglyoxal, OS, or glucose.…”