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

Abstract

We have investigated the effects of long term intake of two unbalanced diets (rich in fat –HF– or protein –HP–) administered under isocaloric conditions to a control balanced diet (pair-feeding) to adult rats. Isocaloric intake of a HF diet did not affect the body weight but increased adiposity, liver-fat deposition, and induced insulin resistance. Gene expression changes in the liver and adipose tissue (increased lipolytic and decreased lipogenic gene expression) could try to compensate for increased adiposity. The HP diet decreased caloric intake, the body weight, the size of subcutaneous adipocytes, and circulating cholesterol. Higher insulin levels apparently not related to insulin resistance were observed. Changes at the gene expression level reflected an adaptation to lower diet carbohydrate content and to the use of amino acids as the energy source. The kidney size 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 the body weight but alters metabolic parameters and kidney size which could be linked to an increased risk of suffering from different pathologies.