Dietary aflatoxin-induced stunting in a novel rat model: evidence for toxin-induced liver injury and hepatic growth hormone resistance.

BACKGROUND: Despite a strong statistical correlation between dietary aflatoxin B1 (AFB1)-exposure and childhood stunting, the causal mechanism remains speculative. This issue is important because of emerging interest in reduction of human aflatoxin exposure to diminish the prevalence and complications of stunting. Pediatric liver diseases cause growth impairment, and AFB1 is hepatotoxic. Thus, liver injury might mediate AFB1-associated growth impairment. We have developed a rat model of dietary AFB1-induced stunting to investigate these questions. METHODS: Newly-weaned rats were given AFB1-supplemented- or control-diets from age 3-9 wk, and then euthanized for serum- and tissue-collection. Food intake and weight were serially assessed, with tibial-length determined at the experimental endpoint. Serum AFB1-adducts, hepatic gene and protein expression, and liver injury markers were quantified using established methodologies. RESULTS: AFB1-albumin adducts correlated with dietary toxin contamination, but such contamination did not affect food consumption. AFB1-exposed animals exhibited dose-dependent wasting and stunting, liver pathology, and suppression of hepatic targets of growth hormone (GH) signaling, but did not display increased mortality. CONCLUSION: These data establish toxin-dependent liver injury and hepatic GH-resistance as candidate mechanisms by which AFB1-exposure causes growth impairment in this mammalian model. Interrogation of modifiers of stunting using this model could guide interventions in at-risk and affected children.

Measurement error of DXA: interpretation of fat and lean mass changes in obese and non-obese children.

Information on reproducibility of dual-energy X-ray absorptiometry (DXA) measurements is essential because DXA is frequently used by clinicians and researchers to assess body composition changes. We estimated measurement error and absolute and relative smallest detectable differences (SDDs) for fat, lean, and bone mass in children. The SDD is the change necessary to be confident that the change is not a consequence of measurement error. Duplicate whole body DXA (Hologic QDR 4500A, Hologic Inc., Waltham, MA) scans were obtained on 32 obese and 34 non-obese children ages 6-19 yr. Absolute (kg) and relative (coefficient of variation) measurement error and SDD were calculated. Absolute SDDs for fat and lean were higher for obese (1.39 and 1.30 kg, respectively) than for non-obese children (0.42 and 0.47 kg, respectively). The %SDD for fat was lower for obese (3.58%) than non-obese children (5.24%), but for lean the %SDD was higher for obese (2.60%) than non-obese children (1.32%). The SDDs for bone mass were similar for obese and non-obese children. An obese child must lose or gain more absolute fat and lean mass than a non-obese child to be confident that the change is not a reflection of measurement error. Overall, SDD values for fat, lean, and bone mass are low.