Evaluation of a Plant-Based Infant Formula Containing Almonds and Buckwheat on Gut Microbiota Composition, Intestine Morphology, Metabolic and Immune Markers in a Neonatal Piglet Model.

A controlled-neonatal piglet trial was conducted to evaluate the impact of a plant-based infant formula containing buckwheat and almonds as the main source of protein compared to a commercially available dairy-based formula on the gut health parameters. Two day old piglets were fed either a plant-based or a dairy-based formula until day 21. Gut microbiome, cytokines, growth and metabolism related outcomes, and intestinal morphology were evaluated to determine the safety of the plant-based infant formula. This study reported that the plant-based formula-fed piglets had a similar intestinal microbiota composition relative to the dairy-based formula-fed group. However, differential abundance of specific microbiota species was detected within each diet group in the small and large intestinal regions and fecal samples. Lactobacillus delbrueckii, Lactobacillus crispatus, and Fusobacterium sp. had higher abundance in the small intestine of plant-based formula-fed piglets compared to the dairy-based group. Bacteroides nordii, Enterococcus sp., Lactobacillus crispatus, Prevotella sp., Ruminococcus lactaris, Bacteroides nordii, Eisenbergiella sp., Lactobacillus crispatus, Prevotella sp., and Akkermansia muciniphila had greater abundance in the large intestine of the plant based diet fed piglets relative to the dairy-based diet group. In the feces, Clostridiales, Bacteroides uniformis, Butyricimonasvirosa, Cloacibacillus porcorum, Clostridium clostridioforme, and Fusobacterium sp. were abundant in dairy-based group relative to the plant-based group. Lachnospiraceae, Clostridium scindens, Lactobacillus coleohominis, and Prevetolla sp. had greater abundance in the feces of the plant-based group in comparison to the dairy-based group. Gut morphology was similar between the plant and the dairy-based formula-fed piglets. Circulatory cytokines, magnesium, triiodothyronine (T3), thyroxine (T4), thyroid stimulating hormone (TSH), vitamin D, vitamin K, and IgE levels were similar among all piglets independent of dietary group. Overall, the present study demonstrated that a plant-based formula with buckwheat and almonds as the primary source of protein can support similar gut microbiota growth and health outcomes compared to a dairy-based infant formula.

Evaluation of the Safety of a Plant-Based Infant Formula Containing Almonds and Buckwheat in a Neonatal Piglet Model.

A randomized neonatal piglet trial was conducted to evaluate the safety and the effects of a plant-based formula containing almonds and buckwheat as the main ingredients on growth and plasma parameters. From postnatal day (PND) 2 to 21, the piglets were fed a dairy-based milk formula (Similac Advance) or a plant-based formula (Else Nutrition) and all piglets were euthanized at day 21. No diarrhea was observed after PND 8 and all the piglets completed the trial. Body growth, kcal intake, the complete plasma count parameters and hematological parameters were within the reference range in both groups. Organ growth and development was similar between the two groups. Plasma glucose was higher in the dairy-based-fed piglets relative to the plant-based at 2 weeks of age. Liver function biomarkers levels were greater in the plasma of the plant-based compared to the dairy-based fed group. In addition, calcium levels were higher in the plant-based fed piglets at 1 week of age. Thus, the plant-based formula tested in this study was well tolerated by the piglets and supported similar growth compared to dairy-based milk formula. Therefore, the results support the safety of the tested plant-based infant formula during the neonatal period in comparison to the dairy-based formula fed group.

Effects of Diet on Late Radiation Injuries in Rats.

It has been speculated that the addition of antioxidants to diet could act as either radioprotectors or as mitigators of radiation injury. In preparation for studies of the mitigation efficacy of antioxidants, rats were placed on a modified version of AIN-76A, the diet typically used in such studies. This AIN-76A diet is refined and has no synthetic antioxidants or isoflavones. Compared to the natural-ingredient Teklad 8904 diet used in previous studies, use of the AIN-76A diet from 1-18 wk after irradiation significantly reduced injury in a radiation nephropathy model. A confirmation study included an additional arm in which the AIN-76A diet was started 2 wk prior to irradiation; again, the switch to AIN-76A postirradiation mitigated radiation nephropathy (p < 0.001), but switching to the AIN-76A diet preirradiation had no effect (p > 0.2). The two diets do not differ in salt content, but the AIN-76A diet is somewhat lower in protein (18% vs. 24%). The protein source (primarily soy in Teklad 8904 vs. casein in AIN-76A) might explain the effects. However, replacing the casein in AIN-76A with soy did not change the mitigation efficacy of the diet (p > 0.2 for comparison of the different AIN-76A diets). A similar study in a rat radiation pneumonitis model also suggested mitigation by postirradiation use of AIN-76A, although the effect was not statistically significant (p = 0.07). In conclusion, base diet alone can have biologically significant effects on organ radiosensitivity, but the mechanistic basis for the effect and its dependence of timing relative to irradiation are unclear.

Stearoyl-CoA desaturase deficiency, hypercholesterolemia, cholestasis, and diabetes.

Previous studies showed that mice deficient in Scd1 had a reduced level of liver triglyceride and an improvement in insulin sensitivity. We studied Scd1(-/-) mice on a very low-fat, high-carbohydrate lipogenic diet. The animals were almost entirely devoid of high-density lipoprotein (HDL). Nonetheless, they were hypercholesterolemic and had cholestasis. These changes were reversible with oil containing both mono- and polyunsaturated fat, but not entirely reversible with just triolein, suggesting that Scd1 deficiency increased the requirement for polyunsaturated fat. We also found that the Scd1(-/-) mice on a normal chow diet had dramatically improved insulin sensitivity. However, leptin(ob/ob) Scd1(-/-) mice had worse diabetes than leptin(ob/ob) Scd1(wt/wt) mice.

Loss of stearoyl-CoA desaturase-1 improves insulin sensitivity in lean mice but worsens diabetes in leptin-deficient obese mice.

The lipogenic gene stearoyl-CoA desaturase (SCD)1 appears to be a promising new target for obesity-related diabetes, as mice deficient in this enzyme are resistant to diet- and leptin deficiency-induced obesity. The BTBR mouse strain replicates many features of insulin resistance found in humans with excess visceral adiposity. Using the hyperinsulinemic-euglycemic clamp technique, we determined that insulin sensitivity was improved in heart, soleus muscle, adipose tissue, and liver of BTBR SCD1-deficient mice. We next determined whether SCD1 deficiency could prevent diabetes in leptin-deficient BTBR mice. Loss of SCD1 in leptin(ob/ob) mice unexpectedly accelerated the progression to severe diabetes; 6-week fasting glucose increased approximately 70%. In response to a glucose challenge, Scd1(-/-) leptin(ob/ob) mice had insufficient insulin secretion, resulting in glucose intolerance. A morphologically distinct class of islets isolated from the Scd1(-/-) leptin(ob/ob) mice had reduced insulin content and increased triglycerides, free fatty acids, esterified cholesterol, and free cholesterol and also a much higher content of saturated fatty acids. We believe the accumulation of lipid is due to an upregulation of lipoprotein lipase (20-fold) and Cd36 (167-fold) and downregulation of lipid oxidation genes in this class of islets. Therefore, although loss of Scd1 has beneficial effects on adiposity, this benefit may come at the expense of beta-cells, resulting in an increased risk of diabetes.

Abdominal obesity in BTBR male mice is associated with peripheral but not hepatic insulin resistance.

Insulin resistance is a common feature of obesity. BTBR mice have more fat mass than most other inbred mouse strains. On a chow diet, BTBR mice have elevated insulin levels relative to the C57BL/6J (B6) strain. Male F1 progeny of a B6 x BTBR cross are insulin resistant. Previously, we reported insulin resistance in isolated muscle and in isolated adipocytes in this strain. Whereas the muscle insulin resistance was observed only in male F1 mice, adipocyte insulin resistance was also present in male BTBR mice. We examined in vivo mechanisms of insulin resistance with the hyperinsulinemic euglycemic clamp technique. At 10 wk of age, BTBR and F1 mice had a >30% reduction in whole body glucose disposal primarily due to insulin resistance in heart, soleus muscle, and adipose tissue. The increased adipose tissue mass and decreased muscle mass in BTBR and F1 mice were negatively and positively correlated with whole body glucose disposal, respectively. Genes involved in focal adhesion, actin cytoskeleton, and inflammation were more highly expressed in BTBR and F1 than in B6 adipose tissue. The BTBR and F1 mice have higher levels of testosterone, which may be related to the pathological changes in adipose tissue that lead to systemic insulin resistance. Despite profound peripheral insulin resistance, BTBR and F1 mice retained hepatic insulin sensitivity. These studies reveal a genetic difference in body composition that correlates with large differences in peripheral insulin sensitivity.

Stearoyl-CoA desaturase deficiency, hypercholesterolaemia, cholestasis and diabetes.

Previous studies have shown that mice deficient in Scd1 have a dramatically reduced level of liver triglyceride and an improvement in insulin sensitivity. The mice are lean and partially protected from obesity induced by leptin deficiency or high fat diets. These results predicted that Scd1(-/-) mice would be protected from the increased serum triglyceride levels that result from a lipogenic diet and might also might protect a diabetes-susceptible obese mouse strain from diabetes. We studied Scd1(-/-) mice on a very low-fat high-carbohydrate lipogenic diet. The animals were almost entirely devoid of high density lipoprotein (HDL). Nonetheless, they were hypercholesterolaemic due to a large increase in low density lipoprotein (LDL). They had a high level of serum bilirubin and bile acids, and the appearance of lipoprotein-X, indicative of cholestasis. These changes were reversible with oil containing both mono- and polyunsaturated fat, but not entirely reversible with just triolein, suggesting that Scd1 deficiency increased the requirement for polyunsaturated fat. We performed hyperinsulinemic-euglycemic clamp experiments and found that the Scd1(-/-) mice on a normal chow diet had dramatically improved insulin sensitivity. But, surprisingly, leptin(ob/ob) Scd1(-/-) mice had worse diabetes than leptin(ob/ob) Scd1(wt/wt) mice. Thus, despite its effects on insulin sensitivity, Scdl deficiency worsens diabetes in leptin-deficient obese mice.

Combined expression trait correlations and expression quantitative trait locus mapping.

Coordinated regulation of gene expression levels across a series of experimental conditions provides valuable information about the functions of correlated transcripts. The consideration of gene expression correlation over a time or tissue dimension has proved valuable in predicting gene function. Here, we consider correlations over a genetic dimension. In addition to identifying coregulated genes, the genetic dimension also supplies us with information about the genomic locations of putative regulatory loci. We calculated correlations among approximately 45,000 expression traits derived from 60 individuals in an F2 sample segregating for obesity and diabetes. By combining the correlation results with linkage mapping information, we were able to identify regulatory networks, make functional predictions for uncharacterized genes, and characterize novel members of known pathways. We found evidence of coordinate regulation of 174 G protein-coupled receptor protein signaling pathway expression traits. Of the 174 traits, 50 had their major LOD peak within 10 cM of a locus on Chromosome 2, and 81 others had a secondary peak in this region. We also characterized a Riken cDNA clone that showed strong correlation with stearoyl-CoA desaturase 1 expression. Experimental validation confirmed that this clone is involved in the regulation of lipid metabolism. We conclude that trait correlation combined with linkage mapping can reveal regulatory networks that would otherwise be missed if we studied only mRNA traits with statistically significant linkages in this small cross. The combined analysis is more sensitive compared with linkage mapping alone.