Major urinary protein 5, a scent communication protein, is regulated by dietary restriction and subsequent re-feeding in mice

Abstract

Major urinary proteins (Mups) are important for rodent scent communication and sexual behaviour. Recent evidence suggests that Mup1 may be regulated by fasting and re-feeding (RF). However, other Mup isoforms are poorly investigated, and data on the impact of long-term dietary restriction (DR) and ad libitum RF on Mup expression are missing. We investigated the effects of long-term 25 per cent DR and subsequent RF on Mup expression in male C57BL6 mice. DR significantly decreased Mup gene expression, hepatic and urinary protein levels compared with ad libitum (AL) fed control mice, with the greatest downregulation found for Mup5 expression. The decline in Mup expression was inverted by six months of RF. Because of inhibitory glucocorticoid response elements in the genomic sequence of the Mup5 gene, the observed inverse correlation of nuclear glucocorticoid receptor levels with Mup expression in response to DR and subsequent RF is a possible regulatory mechanism. Additionally, gene-expression-inhibiting histone deacetylation (H3K9) occurred in the region of the Mup5 gene in response to DR. We assume that Mup may act as a molecular switch linking nutritional status to sexual behaviour of mice, and thereby regulating male fertility and reproduction in response to food supply.

Diversity of major urinary proteins (MUPs) in wild house mice

“…Third, we attempted to explain the disparity between gel-based and gel-free proteomic methods, and unexpectedly we found that gel-based methods do not separate MUP proteins. Our findings indicate the electrophoretic methods used for studying MUPs for the past 80 years215 – to infer similarity2, diversity111315 and other variations in MUPs3036, including hormonal regulation3738 and epigenetic control39, need to be re-evaluated. Gel-based methods provided the basis for the barcode hypothesis and claims that MUPs are highly polymorphic24 – and therefore, the hypothesis that MUPs mediate individual odour and genetic kin recognition (inbreeding avoidance)234613 also needs to be re-evaluated.…”

“…However, further analyses are needed to confirm protein identification, evaluate variation and consistency across all Mup loci, and over a longer time and across different conditions. MUP production is dynamically regulated with changes in age27, health2829, diet30, and social status3132, and we recently found that MUP proteins are differentially regulated when males are placed in competitive social conditions33. Thus, MUP expression profiles are phenotypically plastic, rather than constitutive (developmentally fixed), and studies are needed to investigate how variation and consistency in MUP expression influences individual odor , especially under more natural conditions.…”

Restriction on an Energy-Dense Diet Improves Markers of Metabolic Health and Cellular Aging in Mice Through Decreasing Hepatic mTOR Activity

“…56 In the present study, hepatic Mup expression was significantly reduced in dietaryrestricted mice comparable to restricted mice on a LFD. 12 …”

“…This is in line with recent findings in adult mice showing that DR reduces the number of senescent cells in tissues, including the liver, together with improved telomere maintenance but without actually increasing telomerase activity. 55 It is assumed that DR-induced life-span extension is based on an interplay between nutrition and reproduction 12 and there is evidence linking steroid signaling to nutrient-sensing pathways involving TOR. 56 In the present study, hepatic Mup expression was significantly reduced in dietaryrestricted mice comparable to restricted mice on a LFD.…”

“…[5][6][7] Recent data indicate that lipid composition can also impact the life span of mice subjected to DR. 8 In dietary-restricted rodents, monkeys, and humans, blood pressure and plasma levels of insulin, leptin, C-reactive protein (CRP), triglycerides, and cholesterol are reduced, thereby improving insulin sensitivity and cardiometabolic health. [9][10][11][12][13][14][15] The first results of long-term DR in long-lived primates show promising effects on health status and age-related disease pathologies and mortality, [16][17][18][19] whereas a contrasting study found no beneficial effects on all-cause or age-related mortality, although an improvement in health span. 13 It is of note that clear longevity-related effects in the DR group are particularly absent when the control group is fed a limited amount of food to prevent hyperphagia, 13 and the question was raised whether beneficial effects of DR, at least in primates, may only be due to the elimination of excess fat intake.…”