High fat feeding is associated with stimulation of the hypothalamic-pituitary-adrenal axis and reduced anxiety in the rat
Introduction
Over consumption of a diet rich in saturated fat and sugar is a major factor in the development of obesity and the medical complications which follow such as type 2 diabetes mellitus (T2DM) and cardiovascular disease (Riccardi et al., 2004). There is also evidence that obesity and diabetes can increase the incidence of depression and anxiety in vulnerable individuals (Katon et al., 2004, Kivimaki et al., 2009, Scott et al., 2008, Simon et al., 2006) and it has been suggested that these effects may be associated with impaired regulation of the hypothalamic-pituitary-adrenal (HPA) axis (Pariante and Lightman, 2008, Rosmond et al., 1998, Tannenbaum et al., 1997).
The extent to which obesity is a cause or consequence of impaired HPA axis control remains controversial. In humans, an acute increase in cortisol has been shown to decrease food intake whereas chronic elevations in plasma cortisol, such as those evoked by prolonged exposure to a stressor, promote increased food intake and lead to obesity (Dallman et al., 2004, la Fleur et al., 2007). Glucocorticoids exert their effects in the brain by acting at two classes of receptor, mineralocorticoid receptors (MRs) which bind cortisol and corticosterone with high affinity and glucocorticoid receptors (GRs) which bind the steroids with lower affinity. GRs are only occupied when the concentrations of cortisol or corticosterone are raised by, for example, stressors (Dallman et al., 2000, De Kloet et al., 1998, McEwen, 2008). Persistent changes in the expression of MRs and GRs or polymorphisms affecting ligand binding have been implicated in the psychopathologies underlying depression and anxiety (Herman and Spencer, 1998, Pariante, 2006, van Rossum et al., 2006, Young et al., 2003). Alterations in the expression and regulation of these receptors have also been implicated in the impaired regulation of the HPA axis thought to contribute to the metabolic, physiological and behavioural changes that are associated with obesity (Rosmond, 2003, Tannenbaum et al., 1997).
The neural mechanisms that mediate the effects of obesity on behaviour remain to be established with certainty. High fat feeding can produce behavioural changes in rodents before the development of T2DM, which are also independent of increased insulin resistance (McNeilly et al., 2011, McNeilly et al., 2012). Other studies have shown that chronic HF feeding for 6 weeks reduces 5-hydroxytryptamine (5-HT) release and turnover in the hypothalamus and hippocampus of rodents (Pissios and Maratos-Flier, 2007). It seems reasonable to suggest, therefore, that the effects of HF feeding on measures of stress and anxiety may also reflect changes in the activity of serotonergic neurones. There is an abundance of evidence that serotonergic pathways mediate many of the behavioural responses evoked by exposure to stressful stimuli (Graeff, 2002, Graeff et al., 1996, Neumann et al., 2011). In the present study the effects of HF feeding on the plasma corticosterone and behavioural response to the elevated plus-maze (EPM) test of anxiety have been explored and correlated to changes in 5-HT turnover and GR and MR immunoreactivity in discrete regions of the brain implicated in the psychopathology of anxiety.
Section snippets
Materials
All chemicals were obtained from Sigma unless otherwise stated. Solvents were glass distilled HPLC grade from Fisher Scientific (Loughborough, UK).
Animals
Male Wistar rats (150–175 g, Harlan UK) were housed two per cage and maintained under controlled conditions of light (on 0600–1800 h), temperature (21 ± 1 °C) and humidity (55 ± 5%). Cages were randomly assigned to receive either standard laboratory rat chow or high fat diet (RM1 or 824053 containing 45% AFE fat lard respectively – Special Diet Services,
Physiological and biochemical responses to high fat feeding
As anticipated, following 12 weeks of diet, animals receiving the HF diet were significantly heavier (F[1,28] = 7.954, p < 0.01) than their SC fed counterparts (Table 1). Peri-genital fat pad mass was significantly greater in HF animals (F[1,28] = 18.89, p < 0.01) compared to SC animals, however there was no difference in liver weight. The data presented in Table 1 show that fasting plasma glucose and insulin were significantly greater in HF animals when compared to those receiving standard laboratory
Discussion
Previous studies have shown that short-term (7 days) exposure to an HF diet evokes an anxiolytic-like profile in rats when tested in an EPM (Prasad and Prasad, 1996). We have extended this finding by showing that 12 weeks exposure to a diet high in saturated fat evokes a similar “anxiolytic-like” effect in this test. The HF-fed animals also exhibited an increase in total activity when tested in the EPM. In this context, it is important to note that these measurements were made in an environment
Role of the funding source
This work was supported by a Early Career Grant from the Society for Endocrinology UK to ADM.
Conflict of interest statement
None declared.
Acknowledgement
The authors would like to acknowledge Jacqueline Beattie for her expertise in HPLC analysis.
References (41)
- et al.
The effect of corticosterone in rats submitted to the elevated plus-maze and to pentylenetetrazol-induced convulsions
Prog. Neuropsychopharmacol. Biol. Psychiatry
(1994) - et al.
Behavioral and endocrine change following chronic predatory stress
Physiol. Behav.
(1998) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein–dye binding
Anal. Biochem.
(1976)- et al.
Differential effects of social defeat in rats with high and low locomotor response to novelty
Neuroscience
(2011) - et al.
Role of 5-HT in stress, anxiety, and depression
Pharmacol. Biochem. Behav.
(1996) Central effects of stress hormones in health and disease: understanding the protective and damaging effects of stress and stress mediators
Eur. J. Pharmacol.
(2008)- et al.
High fat feeding promotes simultaneous decline in insulin sensitivity and cognitive performance in a delayed matching and non-matching to position task
Behav. Brain Res.
(2011) - et al.
Chronic stress attenuates glucocorticoid negative feedback: involvement of the prefrontal cortex and hippocampus
Neuroscience
(2003) - et al.
Animal models of depression and anxiety: what do they tell us about human condition?
Prog. Neuropsychopharmacol. Biol. Psychiatry
(2011) - et al.
The HPA axis in major depression: classical theories and new developments
Trends Neurosci.
(2008)
More than satiety: central serotonin signaling and glucose homeostasis
Cell Metab.
Short-term consumption of a diet rich in fat decreases anxiety response in adult male rats
Physiol. Behav.
Effects of swim stress and alpha-MSH acute pre-treatment on brain 5-HT transporter and corticosterone receptor
Pharmacol. Biochem. Behav.
Dietary fat, insulin sensitivity and the metabolic syndrome
Clin. Nutr.
Highly palatable diet consumption increases protein oxidation in rat frontal cortex and anxiety-like behavior
Life Sci.
Behavioural and neurochemical responses evoked by repeated exposure to an elevated open platform
Behav. Brain Res.
Polymorphisms of the glucocorticoid receptor gene and major depression
Biol. Psychiatry
Studies on the possible role of brain 5-HT systems and adrenocortical activity in behavioural responses to nicotine and diazepam in an elevated X-maze
Psychopharmacology (Berl.)
Bottomed out: metabolic significance of the circadian trough in glucocorticoid concentrations
Int. J. Obes. Relat. Metab. Disord.
Chronic stress-induced effects of corticosterone on brain: direct and indirect
Ann. N. Y. Acad. Sci.
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