Amelioration of Insulin Resistance by Whey Protein in a High-Fat Diet-Induced Pediatric Obesity Male Mouse Model.

This study examined whey protein's impact on insulin resistance in a high-fat diet-induced pediatric obesity mouse model. Pregnant mice were fed high-fat diets, and male pups continued this diet until 8 weeks old, then were split into high-fat, whey, and casein diet groups. At 12 weeks old, their body weight, fasting blood glucose (FBG), blood insulin level (IRI), homeostatic model assessment for insulin resistance (HOMA-IR), liver lipid metabolism gene expression, and liver metabolites were compared. The whey group showed significantly lower body weight than the casein group at 12 weeks old (p = 0.034). FBG was lower in the whey group compared to the high-fat diet group (p < 0.01) and casein group (p = 0.058); IRI and HOMA-IR were reduced in the whey group compared to the casein group (p = 0.02, p < 0.01, p < 0.01, respectively). The levels of peroxisome proliferator-activated receptor α and hormone-sensitive lipase were upregulated in the whey group compared to the casein group (p < 0.01, p = 0.03). Metabolomic analysis revealed that the levels of taurine and glycine, both known for their anti-inflammatory and antioxidant properties, were upregulated in the whey group in the liver tissue (p < 0.01, p < 0.01). The intake of whey protein was found to improve insulin resistance in a high-fat diet-induced pediatric obesity mouse model.

Efficacy of Human Recombinant Growth Hormone in Females of a Non-Obese Hyperglycemic Mouse Model after Birth with Low Birth Weight.

We examined whether the administration of growth hormone (GH) improves insulin resistance in females of a non-obese hyperglycemic mouse model after birth with low birth weight (LBW), given that GH is known to increase muscle mass. The intrauterine Ischemia group underwent uterine artery occlusion for 15 min on day 16.5 of gestation. At 4 weeks of age, female mice in the Ischemia group were divided into the GH-treated (Ischemia-GH) and non-GH-treated (Ischemia) groups. At 8 weeks of age, the glucose metabolism, muscle pathology, and metabolome of liver were assessed. The insulin resistance index improved in the Ischemia-GH group compared with the Ischemia group (p = 0.034). The percentage of type 1 muscle fibers was higher in the Ischemia-GH group than the Ischemia group (p < 0.001); the muscle fiber type was altered by GH. In the liver, oxidative stress factors were reduced, and ATP production was increased in the Ischemia-GH group compared to the Ischemia group (p = 0.014), indicating the improved mitochondrial function of liver. GH administration is effective in improving insulin resistance by increasing the content of type 1 muscle fibers and improving mitochondrial function of liver in our non-obese hyperglycemic mouse model after birth with LBW.

Metabolomic profiles of preterm small-for-gestational age infants.

We aimed to characterize the metabolomic profiles in preterm small-for-gestational age (SGA) infants using cord blood. We conducted a gestational age (GA)-matched case-control study that included 30 preterm infants who were categorized into two groups: SGA infants, with a birth weight (BW) < 10th percentile for GA (n = 15) and non-SGA infants, with BW ≥ 10th percentile for GA (n = 15). SGA infants with chromosomal or genetic abnormalities were excluded. At birth, the umbilicus was double-clamped, and the cord blood was sampled from the umbilical vein. Metabolomic analyses were performed using capillary electrophoresis time-of-flight mass spectrometry. The median GA at birth was not significantly different between the two groups [SGA, 32 (26-36) weeks; non-SGA, 32 (25-35) weeks; p = 0.661)]. Of the 255 metabolites analyzed, 19 (7.5%) showed significant differences between SGA and non-SGA infants. There were significant reductions in the carnosine, hypotaurine, and S-methylcysteine levels in SGA infants as compared to non-SGA infants (p < 0.05). Carnosine was correlated with gestational age, BMI before pregnancy, body weight gain during pregnancy (p = 0.002, p = 0.023, and p = 0.020, respectively). In conclusion, preterm SGA infants have low levels of cord blood antioxidative- and antiglycation-related metabolites, making them vulnerable to oxidative stress.

Body Fat-Reducing Effects of Whey Protein Diet in Male Mice.

This study investigated the mechanism of reducing body fat via whey protein diet. Pregnant mice were fed whey or casein, and their offspring were fed by birth mothers. After weaning at 4 weeks, male pups received the diets administered to their birth mothers (n = 6 per group). At 12 weeks of age, body weight, fat mass, fasting blood glucose (FBG), insulin (IRI), homeostatic model assessment of insulin resistance (HOMA-IR), cholesterol (Cho), triglyceride (TG), the expression levels of lipid metabolism-related genes in liver tissues and metabolomic data of fat tissues were measured and compared between the groups. The birth weights of pups born were similar in the two groups. Compared to the pups in the casein group, at 12 weeks of age, pups in the whey group weighed less, had significantly lower fat mass, HOMA-IR and TG levels (p < 0.01, p = 0.02, p = 0.01, respectively), and significantly higher levels of the antioxidant glutathione and the anti-inflammatory 1-methylnicotinamide in fat tissues (p < 0.01, p = 0.04, respectively). No differences were observed in FBG, IRI, Cho levels (p = 0.75, p = 0.07, p = 0.63, respectively) and expression levels of lipid metabolism-related genes. Whey protein has more antioxidant and anti-inflammatory properties than casein protein, which may be its mechanism for reducing body fat.

A Non-Obese Hyperglycemic Mouse Model that Develops after Birth with Low Birthweight.

The number of low birthweight (LBW) infants weighing below 2500 g has not decreased in Japan. This study aimed to develop an adult non-obese hyperglycemic mouse model born with LBW to study the pathogenesis. At 16.5 days of gestation, transient intrauterine ischemia (blocked blood flow in both uterine arteries for 15 min) was performed in a subgroup of pregnant mice (group I). Non-occluded dams were used as sham controls (group C). After birth, female pups in each group were weaned at 4 weeks of age and reared on the normal diet until 8 weeks of age (n = 7). Fasting blood glucose levels, serum immunoreactive insulin (IRI), and body composition were then measured. Metabolite analyses was performed on the liver tissues. Birthweight was significantly lower in group I compared with group C. Pups from group I remained underweight with low fat-free mass and showed hyperglycemia with high serum IRI and homeostasis model assessment of insulin resistance levels, indicating insulin resistance. Metabolite analyses showed significantly reduced adenosine triphosphate and nicotinamide adenine dinucleotide production and increased lactic acid in group I. The pathogenesis of our non-obese hyperglycemic mouse model may be due to increased myogenic insulin resistance based on mitochondrial dysfunction and reduced lean body mass.

Mild MPP+ exposure impairs autophagic degradation through a novel lysosomal acidity-independent mechanism.

Parkinson's disease (PD) is the second most common neurodegenerative disorder, but its underlying cause remains unknown. Although recent studies using PD-related neurotoxin MPP+ suggest autophagy involvement in the pathogenesis of PD, the effect of MPP+ on autophagic processes under mild exposure, which mimics the slow progressive nature of PD, remains largely unclear. We examined the effect of mild MPP+ exposure (10 and 200 µM for 48 h), which induces a more slowly developing cell death, on autophagic processes and the mechanistic differences with acute MPP+ toxicity (2.5 and 5 mM for 24 h). In SH-SY5Y cells, mild MPP+ exposure predominantly inhibited autophagosome degradation, whereas acute MPP+ exposure inhibited both autophagosome degradation and basal autophagy. Mild MPP+ exposure reduced lysosomal hydrolase cathepsin D activity without changing lysosomal acidity, whereas acute exposure decreased lysosomal density. Lysosome biogenesis enhancers trehalose and rapamycin partially alleviated mild MPP+ exposure induced impaired autophagosome degradation and cell death, but did not prevent the pathogenic response to acute MPP+ exposure, suggesting irreversible lysosomal damage. We demonstrated impaired autophagic degradation by MPP+ exposure and mechanistic differences between mild and acute MPP+ toxicities. Mild MPP+ toxicity impaired autophagosome degradation through novel lysosomal acidity-independent mechanisms. Sustained mild lysosomal damage may contribute to PD. We examined the effects of MPP+ on autophagic processes under mild exposure, which mimics the slow progressive nature of Parkinson's disease, in SH-SY5Y cells. This study demonstrated impaired autophagic degradation through a reduction in lysosomal cathepsin D activity without altering lysosomal acidity by mild MPP+ exposure. Mechanistic differences between acute and mild MPP+ toxicity were also observed. Sustained mild damage of lysosome may be an underlying cause of Parkinson's disease. Cover Image for this issue: doi: 10.1111/jnc.13338.

Mobile monitoring along a street canyon and stationary forest air monitoring of formaldehyde by means of a micro-gas analysis system.

A micro-gas analysis system (µGAS) was developed for mobile monitoring and continuous measurements of atmospheric HCHO. HCHO gas was trapped into an absorbing/reaction solution continuously using a microchannel scrubber in which the microchannels were patterned in a honeycomb structure to form a wide absorbing area with a thin absorbing solution layer. Fluorescence was monitored after reaction of the collected HCHO with 2,4-pentanedione (PD) in the presence of acetic acid/ammonium acetate. The system was portable, battery-driven, highly sensitive (limit of detection = 0.01 ppbv) and had good time resolution (response time 50 s). The results revealed that the PD chemistry was subject to interference from O(3). The mechanism of this interference was investigated and the problem was addressed by incorporating a wet denuder. Mobile monitoring was performed along traffic roads, and elevated HCHO levels in a street canyon were evident upon mapping of the obtained data. The system was also applied to stationary monitoring in a forest in which HCHO formed naturally via reaction of biogenic compounds with oxidants. Concentrations of a few ppbv-HCHO and several-tens of ppbv of O(3) were then simultaneously monitored with the µGAS in forest air monitoring campaigns. The obtained 1 h average data were compared with those obtained by 1 h impinger collection and offsite GC-MS analysis after derivatization with o-(2,3,4,5,6-pentafluorobenzyl)hydroxylamine (PFBOA). From the obtained data in the forest, daily variations of chemical HCHO production and loss are discussed.