Saturated high-fat feeding independent of obesity alters hypothalamus-pituitary-adrenal axis function but not anxiety-like behaviour

Overconsumption of dietary fat can elicit impairments in emotional processes and the response to stress. While excess dietary lipids have been shown to alter hypothalamus-pituitary-adrenal (HPA) axis function and promote anxiety-like behaviour, it is not known if such changes rely on elevated body weight and if these effects are specific to the type of dietary fat. The objective of this study was to investigate the effect of a saturated and a monounsaturated high-fat diet (HFD) on HPA axis function and anxiety-like behaviour in rats. Biochemical, metabolic and behavioural responses were evaluated following eight weeks on one of three diets: (1) a monounsaturated HFD (50%kcal olive oil), (2) a saturated HFD (50%kcal palm oil), or (3) a control low-fat diet. Weight gain was similar across the three diets while visceral fat mass was elevated by the two HFDs. The saturated HFD had specific actions to increase peak plasma levels of corticosterone and tumour-necrosis-factor-alpha and suppress mRNA expression of glucocorticoid and mineralocorticoid receptors, corticotropin-releasing hormone and 11β-hydroxysteroid dehydrogenase-1 in the paraventricular nucleus of the hypothalamus. Both HFDs enhanced the corticosterone-suppressing response to dexamethasone administration without affecting the physiological response to a restraint stress and failed to increase anxiety-like behaviour as measured in the elevated-plus maze and open field tests. These findings demonstrate that prolonged intake of saturated fat, without added weight gain, increases CORT and modulates central HPA feedback processes. That saturated HFD failed to affect anxiety-like behaviour can suggest that the anxiogenic effects of prolonged high-fat feeding may rely on more pronounced metabolic dysfunction.