Intrauterine Low-Protein Diet Exacerbates Abnormal Development of the Urinary System in Gen1-Mutant Mice

<b><i>Background:</i></b> <i>Gen1</i> mutation can cause various phenotypes of congenital anomaly of the kidney and urinary tract (CAKUT). An intrauterine low-protein isocaloric diet can also cause CAKUT phenotypes in offspring. However, single factors such as gene mutation or abnormal environmental factor during pregnancy can only explain part of the pathogenesis of CAKUT. <b><i>Objectives:</i></b> A low-protein isocaloric diet was fed to <i>Gen1</i>-mutant mice throughout pregnancy to establish a <i>Gen1</i>-mutant mouse model exposed to a low-protein isocaloric intrauterine environment. The mice were divided into 4 groups: normal (22%) protein diet (ND) + wild-type mice (CON group), ND + Gen1^PB/+ mice (Gen1^PB/+ group), low (6%)-protein isocaloric diet (LD) + wild-type mice (LD group), and the LD + Gen1^PB/+ groups. <b><i>Methods:</i></b> The experimental design included observing proportion and distribution of CAKUT phenotypes of neonatal mice; evaluating the number of ureteric buds (UBs) on embryonic day (E) 11.5, the location of UBs on E11.5, and length of the common nephric duct (CND); isolating embryonic kidneys on E11.5 from the Gen1^PB/+ group and culturing embryonic kidneys in medium containing 10% serum or serum-free medium to observe the branching of UBs; and detecting the p-PLCγ, p-Akt, and p-ERK1/2 in UBs and CND on E11.5, as well as the apoptosis and proliferation of tissues by immunofluorescence staining. <b><i>Results:</i></b> We found that the incidence of CAKUT in offspring of Gen1^PB/+ mice under an intrauterine low-protein isocaloric diet environment was significantly increased, and a duplicated collecting system was the dominant phenotype of CAKUT. During the early stage of metanephric development, ectopic protrusion of UBs may appear and lower locations of UBs in Gen1^PB/+ mice under an intrauterine low-protein isocaloric diet environment and the number of UB branches in the serum-free culture condition significantly decreased. Further examination revealed that p-PLCγ signaling and tissue apoptosis were abnormal in UBs and the CND at the early stage of kidney development. <b><i>Conclusions:</i></b> The aforementioned findings suggest that an intrauterine low-protein isocaloric diet can aggravate the occurrence of CAKUT in <i>Gen1</i>-mutant mice, which might affect key steps in the metanephric development, such as the protrusion of UBs, which might be related to mediate UBs and CND apoptosis through p-PLCγ signaling.

GROWTH AND NUTRIENT DIGESTIBlLITY OF JELAWAT (Leptobarbus hoeveni) FRY FED WITH VARIOUS DIETARY PROTEIN LEVELS

A growth and nutnent dtgesttbility study was executed for jelawat fry in the laboratory. The fry (40 day-old) were reared in 9 aquariums of 37.5L water volume at 30 per tank and fed an isocaloric diet(42kcal) contatning 3 dietary protein levels (33, 40, 47%) at 10% of body weigh tadayfor 49 days. Biomass was weighed fortnightly.

Measuring VLDL1-Triglyceride and VLDL2-Triglyceride Kinetics in Men: Effects of Dietary Control on Day-to-Day Variability

The aim of this study was to assess the impact of dietary control on VLDL1- and VLDL2-TG kinetics and associated metabolic parameters. Twelve overweight/obese men were randomized to a provided 3 day isocaloric diet with fixed macronutrient composition (diet group, n=6) or to their regular unrestricted diet (non-diet group, n=6). VLDL1- and VLDL2-TG turnovers were measured twice 2–4 weeks apart, using primed-constant infusion of ex vivo labeled [1-14C]VLDL1-TG and [9,10-3H]VLDL2-TG. Isocaloric diet intervention lowered the difference in the mean of both VLDL2-TG secretion and clearance rate (p<0.01), and the coefficient of variation (CV) of VLDL2-TG clearance rate (p<0.05). The difference in mean and CV of the other kinetic estimates (VLDL1-TG secretion, clearance and oxidation rate) were lowered, but not significantly. The CV’s of total triglyceride, VLDL1-TG, and VLDL2-TG concentrations were significantly lowered by diet intervention compared to regular diet; total triglyceride (31%–5%, p<0.01), VLDL1-TG (42%–9%, p<0.01), and VLDL2-TG (36%–10%, p<0.01). In conclusion, VLDL1- and VLDL2-TG kinetics show great day-to-day variability, which may be diminished by diet intervention. Therefore, standardized macronutrient intake prior to study days improves the probability of demonstrating significant outcomes of cross-sectional and intervention studies of VLDL1-TG and VLDL2-TG kinetics and metabolism.

Maternal Low Protein Isocaloric Diet Suppresses Pancreatic β-Cell Proliferation in Mouse Offspring via miR-15b

The mechanism underlying the increased susceptibility of type 2 diabetes in offspring of maternal malnutrition is poorly determined. Here we tested the hypothesis that functional microRNAs (miRNAs) mediated the maternal low-protein (LP) isocaloric diet induced pancreatic β-cell impairment. We performed miRNA profiling in the islets from offspring of LP and control diet mothers to explore the potential functional miRNAs responsible for β-cell dysfunction. We found that LP offspring exhibited impaired glucose tolerance due to decreased β-cell mass and insulin secretion. Reduction in the β-cell proliferation rate and cell size contributed to the decreased β-cell mass. MiR-15b was up-regulated in the islets of LP offspring. The up-regulated miR-15b inhibited pancreatic β-cell proliferation via targeting cyclin D1 and cyclin D2. Inhibition of miR-15b in LP islet cells restored β-cell proliferation and insulin secretion. Our findings demonstrate that miR-15b is critical for the regulation of pancreatic β-cells in offspring of maternal protein restriction, which may provide a further insight for β-cell exhaustion originated from intrauterine growth restriction.

The Influence of Alcohol Consumption in Conjunction with Sex Hormone Deficiency on Ca/P Ratio in Rats

Deficiency of sex hormones and excessive alcohol consumption are factors that have been related to alterations in the pattern of bone mineralization and osteoporosis. The aim of this study was to evaluate possible alterations in the calcium/phosphorus (Ca/P) ratio in the femur of rats subjected to sex hormone deficiency and/or alcohol consumption.Methods. Female and male Wistar rats (n=108) were divided into ovariectomized (Ovx), orchiectomized (Orx), or sham-operated groups and subdivided according to diet: alcoholic diet (20% alcohol solution), isocaloric diet, andad libitumdiet. The diets were administered for 8 weeks. The Ca/P ratio in the femur was analyzed by energy dispersive micro-X-ray spectrometer (μEDX).Results. Consumption of alcohol reduced the Ca/P ratio in both females and males. The isocaloric diet reduced the Ca/P ratio in females. In groups with thead libitumdiet, the deficiency of sex hormones did not change the Ca/P ratio in females or males. However, the combination of sex hormone deficiency and alcoholic diet presented the lowest values for the Ca/P ratio in both females and males.Conclusions. There was a reduced Ca/P ratio in the femur of rats that consumed alcohol, which was exacerbated when combined with a deficiency of sex hormones.