Significant genotype by diet (G × D) interaction effects on cardiometabolic responses to a pedigree-wide, dietary challenge in vervet monkeys (Chlorocebus aethiops sabaeus).

Nutrient composition of a diet (D) has been shown to interact with genetic predispositions (G) to affect various lipid phenotypes. Our aim in this study was to confirm G × D interaction and determine whether the interaction extends to other cardiometabolic risk factors such as glycemic measures and body weight. Subjects were vervet monkeys (Chlorocebus aethiops sabaeus; n = 309) from a multigenerational pedigreed colony initially fed with a plant-based diet, standard primate diet (18% calories from protein, 13% from fat, and 69% from carbohydrates), and subsequently challenged for 8 weeks with a diet modeled on the typical American diet (18% calories from protein, 35% from fat, and 47% from carbohydrates). Our results showed that although exposure to the challenge diet did not result in significant changes in weight, most lipid and glycemic biomarkers moved in an adverse direction (P < 0.01). Quantitative genetic analyses showed that cardiometabolic phenotypes were significantly heritable under both dietary conditions (P < 0.05), and there was significant evidence of G × D interaction for these phenotypes. We observed significant differences in the additive genetic variances for most lipid phenotypes (P < 10(-4) ), indicating that the magnitude of genetic effects varies by diet. Furthermore, genetic correlations between diets differed significantly from 1 with respect to insulin, body weight, and some lipid phenotypes (P < 0.01). This implied that distinct genetic effects are involved in the regulation of these phenotypes under the two dietary conditions. These G × D effects confirm and extend previous observations in baboons (Papio sp.) and suggest that mimicking the typical human nutritional environment can reveal genetic influences that might not be observed in animals consuming standard, plant-based diets.

Non-contrasted computed tomography for the accurate measurement of liver steatosis in obese patients.

BACKGROUND: Hepatic macrosteatosis (HMS) is prevalent among high BMI patients, but a lack of validation of non-invasive measures of liver fat hampers non-alcoholic liver disease (NAFLD) investigation in general. Recent work suggests BMI adjusted, non-contrasted computed tomography (nc-CT) attenuation data (Hounsfield units) reflects liver fat accumulation in a normal weight population. However, this and other CT-based HMS studies have only approximated macrosteatosis (%) histologically, but have not validated findings with chemical liver triglyceride (TG) concentrations (mg/gram protein). Also, all previous CT based steatosis studies excluded high BMI subjects, whose habitus may affect properties of the scan. We hypothesized that in high BMI patients nc-CT attenuation measurements expressed in Hounsfield units (HU) accurately estimate liver triglyceride concentrations as well as histological macrosteatosis. METHODS: With informed consent, 15 patients underwent nc-CT scan of the abdomen prior to weight loss surgery with intraoperative wedge and core needle liver biopsy. Mean left lobe nc-CT Hounsfield units (CT(L)), liver TG (mg/g Pr), HMS (%), BMI (kg/m(2)), liver-spleen index (CT(L/S) = hepatic HU/splenic HU), and liver-spleen difference (CT(L-S) = hepatic HU - splenic HU) were a priori outcomes. RESULTS: In 15 patients (11 female) with a BMI of 44.4 ± 1.1 (mean ± SEM), CT(L/S), CT(L-S), and CT(L) measures were significantly associated with liver TG concentrations (r = -0.80, P < 0.001; r = -0.80, P < 0.001; and r = -0.71, P < 0.01, respectively; Table 1). Macrosteatosis (%) and liver triglyceride concentration were positively associated (r = 0.83; P < 0.0001). BMI did not correlate strongly to liver triglyceride (r = 0.44, P = NS). CONCLUSION: Estimates of liver fat obtained by nc- CT scans (esp. CT(L/S), CT(L-S)) correlate to chemical measurement of liver triglyceride concentrations, suggesting non-contrasted CT may be a suitable non-invasive "gold standard" for hepatic steatosis quantification in these patients.