A Brazilian regional basic diet-induced chronic malnutrition drives liver inflammation with higher ApoA-I activity in C57BL6J mice

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)-1b immunohistochemistry, and tumor necrosis factor (TNF)-a 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 (Po0.05). Higher hepatic TNF-a (Po0.001) and IL-10 (Po0.01) 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 (presumably Kupffer cells) were found in the undernourished group. No statistical difference in serum ALT was found. There was also a significant increase in ApoA-I 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.

Protein Malnutrition in BALB/c Mice: An Experimental Model Resembling Clinical Scenario

“…19 Literature also indicates that the increase in Kupffer cells results from malnutrition. 36 Considering this evidence, our study confirms that the developed mice model is stable and clinically relevant.…”

Schistosoma mansoni Infection Is Impacted by Malnutrition

“…Data published by others demonstrate malnutrition even in mice fed with diets containing 8% protein. The different outcome observed in our study can be attributed to differences in the food composition, as previous studies used more restricted diets with multi-deficiency in macronutrients (mainly proteins and lipids), as well as minerals and vitamins ( Teodósio et al, 1990 ; Coutinho et al, 1992 ; Rezende et al, 1997a ; Barros et al, 2014 ; Santos et al, 2020 ).…”

Angiotensin-(3–4) normalizes the elevated arterial blood pressure and abnormal Na+/energy handling associated with chronic undernutrition by counteracting the effects mediated by type 1 angiotensin II receptors

“…These alterations, which were totally or partially reversed by blockade of this axis with Losartan, or by activation of the counteracting Ang II)AT 2 R axis by Ang-(3-4) [11,12], occurred despite an increased caloric intake and a dietary Na + content 20% lower than in the CTRL diet. Three points deserve consideration: (i) RBD administration is initiated immediately after weaning, a life period when occurs rapid and definitive developmental events [29,30]; (ii) this diet mimics those consumed in vast regions of undeveloped countries [5,31,32]; and (iii) the extremely poor quality of the reduced protein content, the leading cause of morbidity and mortality in today's world [33,34].…”