Metabolic Syndrome (MetS) increases the risk of developing
type 2 diabetes mellitus and cardiovascular complications. The crosstalk between the hypothalamus and periphery is vital for regulating food intake and energy homeostasis. However, it is impaired during MetS. The present study aimed to compare the distinct central and peripheral metabolic derangements induced by a high-
fructose drink or high-fat diet, as well as the possible intervention by
fenofibrate. Rats were divided into five groups: standard chow diet (SCD) group, high-
fructose group (FR), high-fat group (HF), FR plus
fenofibrate group (FR-F), and HF plus
fenofibrate group (HF-F). FR and HF groups showed
hyperglycemia,
hyperinsulinemia,
hypertriglyceridemia, hyperleptinemia, steatosis, and adipocyte
hypertrophy. This was associated with elevated circulating levels of proinflammatory
cytokines and
free fatty acids (FFAs). The latter mediators are involved in the hypothalamic
inflammation and dysregulation of signaling cascades that control food intake and
glucose homeostasis. The effects were more pronounced in the HF group than FR group, which were matched with the observed higher levels of plasma FFAs and
cytokines.
Fenofibrate administration improved not only the peripheral metabolic disturbances, but also the central disturbances associated with
insulin resistance induced by FR or HF diet. This study sheds light on the pivotal role of the hypothalamus in diet-induced MetS. Furthermore, the study suggests the utmost importance of developing a standardized model of
metabolic syndrome in place of the great diversity between available models, which can induce different effects and negatively impact the validity of prospective studies.