In Vivo Assessment of Antioxidant Potential of Human Milk Treated by Holder Pasteurization or High Hydrostatic Pressure Processing: A Preliminary Study on Intestinal and Hepatic Markers in Adult Mice.

Preterm infants are highly susceptible to oxidative stress due to an imbalance between endogenous oxidant and antioxidant systems. In addition, these newborns are frequently fed with donor milk (DM) treated by Holder pasteurization (HoP) at 62.5 °C for 30 min, which is known to alter numerous heat-sensitive factors, including some antioxidants. High hydrostatic pressure (HHP) processing was recently proposed as an innovative method for the treatment of DM. The present study aimed to measure the redox balance of HoP- and HHP-DM and to study, in vivo, the effects of HoP- and HHP-DM on the gut and liver. H2O2, vitamin A and vitamin E (α- and γ-tocopherols) concentrations, as well as the total antioxidant capacity (TAC), were measured in raw-, HoP- and HHP-DM. The gene expression level of antioxidant systems and inflammatory response were quantified in the ileum and liver of adult mice after 7 days of oral administration of HoP- or HHP-DM. HoP reduced the γ-tocopherol level, whereas HHP treatment preserved all vitamins close to the raw milk level. The milk H2O2 content was reduced by HHP but not by HoP. The total antioxidant capacity of DM was reduced after HHP processing measured by PAOT-Liquid® technology but was unaffected after measurement by ORAC assay. In mice, HHP-DM administration induced a stimulation of antioxidant defenses and reduced some inflammatory markers in both the ileum and liver compared to HoP-DM treatment. Our preliminary study suggests that the HHP processing of DM may better protect preterm infants from gut and liver pathologies compared to HoP, which is currently used in most human milk banks.

Central chronic apelin infusion decreases energy expenditure and thermogenesis in mice.

Apelin is a bioactive peptide involved in the control of energy metabolism. In the hypothalamus, chronic exposure to high levels of apelin is associated with an increase in hepatic glucose production, and then contributes to the onset of type 2 diabetes. However, the molecular mechanisms behind deleterious effects of chronic apelin in the brain and consequences on energy expenditure and thermogenesis are currently unknown. We aimed to evaluate the effects of chronic intracerebroventricular (icv) infusion of apelin in normal mice on hypothalamic inflammatory gene expression, energy expenditure, thermogenesis and brown adipose tissue functions. We have shown that chronic icv infusion of apelin increases the expression of pro-inflammatory factors in the hypothalamus associated with an increase in plasma interleukin-1 beta. In parallel, mice infused with icv apelin exhibit a significant lower energy expenditure coupled to a decrease in PGC1alpha, PRDM16 and UCP1 expression in brown adipose tissue which could explain the alteration of thermogenesis in these mice. These data provide compelling evidence that central apelin contributes to the development of type 2 diabetes by altering energy expenditure, thermogenesis and fat browning.

Brain glucagon-like peptide 1 signaling controls the onset of high-fat diet-induced insulin resistance and reduces energy expenditure.

Glucagon-like peptide-1 (GLP-1) is a peptide released by the intestine and the brain. We previously demonstrated that brain GLP-1 increases glucose-dependent hyperinsulinemia and insulin resistance. These two features are major characteristics of the onset of type 2 diabetes. Therefore, we investigated whether blocking brain GLP-1 signaling would prevent high-fat diet (HFD)-induced diabetes in the mouse. Our data show that a 1-month chronic blockage of brain GLP-1 signaling by exendin-9 (Ex9), totally prevented hyperinsulinemia and insulin resistance in HFD mice. Furthermore, food intake was dramatically increased, but body weight gain was unchanged, showing that brain GLP-1 controlled energy expenditure. Thermogenesis, glucose utilization, oxygen consumption, carbon dioxide production, muscle glycolytic respiratory index, UCP2 expression in muscle, and basal ambulatory activity were all increased by the exendin-9 treatment. Thus, we have demonstrated that in response to a HFD, brain GLP-1 signaling induces hyperinsulinemia and insulin resistance and decreases energy expenditure by reducing metabolic thermogenesis and ambulatory activity.