Mammary gland health plays a key role in maintaining lactation persistency. As a well-known factor involved in physiological processes, the role of oxygen levels in bovine mammary health and lactation persistency remains to be investigated. The present study aimed at investigating the potential regulatory role of hypoxia in the mammary gland of dairy cows with different lactation persistency. Sixty-one Holstein dairy cows were selected for a 180-day experiment at approximately 88 days in milk (DIM). Plasma, milk and mammary tissue samples from 61 cattle were collected on experimental days 0, 90 and 180 (corresponding to 88, 178 and 268 DIM), respectively. Of the 61 cows, 12 cows with high lactation persistency (HP) and 12 with low lactation persistency (LP) were selected for the current study. No difference was observed in milk yield between two groups on d 0 (Pd 0 = 0.67), whereas differences emerged between animals with different lactation persistency at d 105 (Pd 105 = 0.03) until d 180 (Pd 180 < 0.01). The level of mammary apoptosis was significantly higher in the LP group than in the HP cows (Ppersistency < 0.01). In the oxygen-related variables, plasma concentration of hypoxia-inducible factor 1α (HIF-1α) was higher in the LP cows than in the HP group (Ppersistency < 0.01), especially on d 0 (Pd 0 < 0.01). Compared with HP cows, LP cows had a higher malonaldehyde (Pd 180 = 0.01) and a lower activity of inducible nitric oxide synthase (Pd 180 = 0.01) on d 180, suggesting a possible oxygen alteration between cows with different lactation persistency. RNA-sequencing analysis of the mammary gland on d 0 revealed that HIF-1 associated molecules may play a role in driving mammary gland apoptosis in dairy cows. A lower lactation persistency of dairy cows may be resulted from the altered HIF-1α in the mammary gland.

Angiopoietin-like protein 4 (ANGPTL4) is a lipoprotein lipase inhibitor that is involved in lipid metabolism and angiogenesis. Animal studies have suggested that the ANGPTL4 protein is modulated by the gut microbiota, possibly through increased concentrations of SCFA, such as C4, found in whole-fat milk or as a result of fermentation of inulin. This study investigated whether a standardised diet either high in fat content or supplemented with inulin powder would increase plasma ANGPTL4 in overweight men and whether this increase was mediated through a compositional change of the gut microbiota. The study had a crossover design with three arms, where participants were given a standardised isoenergetic diet supplemented with inulin powder, whole-fat milk or water (control). Plasma and urine samples were collected before and after each intervention period. Faecal samples and adipose tissue biopsies were collected after each intervention period. The study included twenty-one participants of whom eighteen completed the study. The dietary interventions did not change ANGPTL4 plasma concentration, nor was plasma ANGPTL4 associated with plasma lipids, TAG or NEFA concentration. The relative abundance of bifidobacteria following the inulin diet was higher, compared with the control diet. However, the changes in microbiota were not associated with plasma ANGPTL4 and the overall composition of the microbiota did not change between the dietary periods. Although weight was maintained throughout the dietary periods, weight was negatively associated with plasma ANGPTL4 concentration. In the adipose tissue, ANGPTL4 expression was correlated with leptin expression, but not with hypoxia-inducible factor 1α (HIF-1α) expression.