Sustained exposure to diets with an unbalanced macronutrient proportion alters key genes involved in energy homeostasis and obesity-related metabolic parameters in rats

[eng] We have investigated the effects of long term intake of two unbalanced diets (rich in fat -HF- or protein -HP-) administered in isocaloric conditions to a control balanced diet (pair-feeding) to adult rats. Isocaloric intake of a HF diet did not affect body weight but increased adiposity, liver-fat deposition, and induced insulin resistance. Gene expression changes in liver and adipose tissue (increased lipolytic and decreased lipogenic gene expression) could try to compensate for increased adiposity. HP diet decreased caloric intake, body weight, size of subcutaneous adipocytes, and circulating cholesterol. Higher insulin levels apparently not related to insulin resistance were observed. Changes at gene expression level reflected an adaptation to lower diet carbohydrate content and to the use of amino acids as energy source. Kidney size was increased in HP-fed animals but serum creatinine was not affected. Circulating TNF-alpha levels were higher in both dietary models. Thus, a long-term increase in dietary fat proportion produces alterations related to metabolic syndrome even in the absence of increased body weight, whereas an increase in diet protein content reduces body weight but alters metabolic parameters and kidney size which could be linked to increased risk of suffering different pathologies