Normobaric hypoxia shows enhanced FOXO1 signaling in obese mouse gastrocnemius muscle linked to metabolism and muscle structure and neuromuscular innervation.

Skeletal muscle relies on mitochondria for sustainable ATP production, which may be impacted by reduced oxygen availability (hypoxia). Compared with long-term hypoxia, the mechanistic in vivo response to acute hypoxia remains elusive. Therefore, we aimed to provide an integrated description of the Musculus gastrocnemius response to acute hypoxia. Fasted male C57BL/6JOlaHsd mice, fed a 40en% fat diet for six weeks, were exposed to 12% O2 normobaric hypoxia or normoxia (20.9% O2) for six hours (n = 12 per group). Whole-body energy metabolism and the transcriptome response of the M. gastrocnemius were analyzed and confirmed by acylcarnitine determination and Q-PCR. At the whole-body level, six hours of hypoxia reduced energy expenditure, increased blood glucose and tended to decreased the respiratory exchange ratio (RER). Whole-genome transcriptome analysis revealed upregulation of forkhead box-O (FOXO) signalling, including an increased expression of tribbles pseudokinase 3 (Trib3). Trib3 positively correlated with blood glucose levels. Upregulated carnitine palmitoyltransferase 1A negatively correlated with the RER, but the significantly increased in tissue C14-1, C16-0 and C18-1 acylcarnitines supported that ß-oxidation was not regulated. The hypoxia-induced FOXO activation could also be connected to altered gene expression related to fiber-type switching, extracellular matrix remodeling, muscle differentiation and neuromuscular junction denervation. Our results suggest that a six-hour exposure of obese mice to 12% O2 normobaric hypoxia impacts M. gastrocnemius via FOXO1, initiating alterations that may contribute to muscle remodeling of which denervation is novel and warrants further investigation. The findings support an early role of hypoxia in tissue alterations in hypoxia-associated conditions such as aging and obesity.

Sensory characteristics of human milk: Association between mothers' diet and milk for bitter taste.

It is unknown how consumption of bitter foods and beverages in the maternal diet influences sensory properties of fresh human milk. The aims of this study were (1) to determine the sensory characteristics of fresh human fore and hind milk, (2) to establish relationships between sensory properties and composition of fresh human milk, and (3) to assess the relationship between bitterness of the maternal diet and human milk. Twenty-two lactating mothers generated sensory terms to describe perception of their milk and received training on sensory attribute intensity rating. Mothers kept a 24-h food diary followed by a sensory self-assessment of their fore and hind milks. The odor of human fresh milk was described as neutral, creamy, and sweet, taste as sweet and bitter, and mouthfeel as thin, watery, smooth, and fatty. Sweetness was equivalent to 1.53 g of sucrose/100 mL and was not significantly different between fore and hind milk. Fore milk was significantly less creamy, less fatty, thinner, more watery, and lower in vanilla flavor intensity than hind milk. Carbohydrate content of human milk was positively correlated with sweetness and glutamic acid content with umami. The bitterness of the diet consumed 24 h before lactation was moderately positively correlated with bitterness of fore milk, but not hind milk. We conclude that the consumption of bitter foods may influence the bitterness of human fore milk, which may be another way for breastfed children to learn to accept bitter vegetables and, hence, develop healthier food preferences.

Short Communication: Differences in Levels of Free Amino Acids and Total Protein in Human Foremilk and Hindmilk.

Free amino acids (FAAs) in human milk are indicated to have specific functional roles in infant development. Studies have shown differences between human milk that is expressed at the beginning of a feed (i.e., foremilk) and the remainder of the milk expressed (i.e., hindmilk). For example, it is well established that human hindmilk is richer in fat and energy than foremilk. Hence, exclusively feeding hindmilk is used to enhance weight gain of preterm, low birthweight infants. Whether FAAs occur differently between foremilk and hindmilk has never been reported, but given their bioactive capacities, this is relevant to consider especially in situations where hindmilk is fed exclusively. Therefore, this study analyzed and compared the FAA and total protein content in human foremilk and hindmilk samples donated by 30 healthy lactating women. The total protein content was found to be significantly higher in hindmilk (p < 0.001), whereas foremilk contained a significantly higher total content of FAAs (p = 0.015). With regards to individual FAAs, foremilk contained significantly higher levels of phenylalanine (p = 0.009), threonine (p = 0.003), valine (p = 0.018), alanine (p = 0.004), glutamine (p < 0.001), and serine (p = 0.012) than hindmilk. Although statistical significance was reached, effect size analysis of the milk fraction on FAA levels in milk revealed that the observed differences were only small. To what extent these differences are of physiological importance for infant development remains to be examined in future research.