Abstract
Malnutrition is still considered endemic in many developing countries. Malnutrition-enteric infections may cause lasting deleterious effects on lipid metabolism, especially in children living in poor settings. The regional basic diet (RBD), produced to mimic the Brazilian northeastern dietary characteristics (rich in carbohydrate and low in protein) has been used in experimental malnutrition models, but few studies have explored the effect of chronic RBD on liver function, a central organ involved in cholesterol metabolism. This study aimed to investigate whether RBD leads to liver inflammatory changes and altered reverse cholesterol metabolism in C57BL6/J mice compared to the control group, receiving a standard chow diet. To evaluate liver inflammation, ionized calcium-binding adapter protein-1 (IBA-1) positive cell counting, interleukin (IL)-1β immunohistochemistry, and tumor necrosis factor (TNF)-α and IL-10 transcription levels were analyzed. In addition, we assessed reverse cholesterol transport by measuring liver apolipoprotein (Apo)E, ApoA-I, and lecithin-cholesterol acyltransferase (LCAT) by RT-PCR. Furthermore, serum alanine aminotransferase (ALT) was measured to assess liver function. RBD markedly impaired body weight gain compared with the control group (P<0.05). Higher hepatic TNF-α (P<0.0001) and IL-10 (P=0.001) mRNA levels were found in RBD-challenged mice, although without detectable non-alcoholic fatty liver disease. Marked IBA-1 immunolabeling and increased number of positive-IBA-1 cells were found in the undernourished group. No statistical difference in serum ALT was found. There was also a significant increase in ApoA mRNA expression in the undernourished group, but not ApoE and LCAT, compared with the control. Altogether our findings suggested that chronic RBD-induced malnutrition leads to liver inflammation with increased ApoA-I activity.
Highlights
Malnutrition is still endemic in many parts of the developing world where poverty coexists with infectious diseases, much of it associated with precarious sanitation and hygiene [1]
We have addressed whether the regional basic diet (RBD), as a model of chronic malnutrition in weanling mice, could have a pro-inflammatory effect on the liver, with a focus on reverse cholesterol transport, which may have long-term consequences on liver metabolism with aging
Body weight gain RBD induced a profound reduction in body weight gain compared to the nourished control group (Po0.05) as soon as the fourth day under RBD-feeding and throughout the remaining experimental protocol
Summary
Malnutrition is still endemic in many parts of the developing world where poverty coexists with infectious diseases, much of it associated with precarious sanitation and hygiene [1]. Wistar rats receiving a low protein diet show growth impairment, edema, liver steatosis, Malnutrition inflammatory effects on liver hypoalbuminemia, and anemia, which are common characteristics of human kwashiorkor [7]. The composition of diets available to weanling children features both low protein and high carbohydrate concentrations [8,9], including the Brazilian semi-arid northeast, one of the poorest regions in the country [10]. Our group has utilized the regional basic diet (RBD), enriched in carbohydrate and with low protein concentration, to induce experimental malnutrition with disrupted intestinal barrier function [11] and assessed intestinal inflammatory markers [12]. Chronic malnutrition-driven stunting has been recognized to be associated with lowgrade systemic inflammation in children [13]
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