Dataset Information

Female sex hormones are necessary for the metabolic effects mediated by loss of Interleukin 18 signaling.

ABSTRACT:

Objective

Interleukin (IL)-18 plays a crucial role in maintaining metabolic homeostasis and levels of this cytokine are influenced by gender, age, and sex hormones. The role of gender on IL-18 signaling, however, is unclear. We hypothesized that the presence of female sex hormone could preserve the metabolic phenotype of the IL-18R^-/- animals.

Methods

We studied female mice with a global deletion of the α isoform of the IL-18 receptor (IL-18R^-/-) and littermates control. Three studies were done: 1) animals fed a high fat diet (HFD) for 16 weeks; 2) animals fed chow diet for 72 weeks and 3) animals (3 weeks-old) randomized to either bilateral ovariectomy (OVX) or control surgery (SHAM) and followed for 16 weeks.

Results

Female IL-18R^-/- mice gained less weight and maintained glucose homeostasis on a chow diet compared with HFD, but no differences between genotypes were observed. The maintenance of body weight and glucose homeostasis in IL-18R^-/- mice was lost with aging. By 72 weeks of age, IL-18R^-/- mice became heavier compared with WT mice due to an increase in both visceral and subcutaneous adiposity and displayed glucose intolerance. OVX did not affect body weight in IL-18R^-/- mice but exacerbated glucose intolerance and impaired liver insulin signaling when compared with SHAM mice.

Conclusions

Female mice harboring a global deletion of the IL-18R, only present the same phenotype as reported in male IL-18R^-/- mice if they are aged or have undergone OVX, in which circulating estrogen is likely to be blunted. The role of estrogen signaling in the protection against altered metabolic homeostasis in IL-18R^-/- mice appears to be mediated by liver insulin signaling. We therefore suggest that the metabolic effects mediated by loss of IL-18 signaling are only present in a female sex hormone free environment.

SUBMITTER: Lindegaard B

PROVIDER: S-EPMC6001917 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:AimsFirst, to discuss sex differences in auditory function between women and men, and whether cyclic fluctuations in levels of female sex hormones (i.e., estradiol and progesterone) affect auditory function in pre-menopausal and post-menopausal women. Second, to systematically review the literature concerning the discussed patterns in order to give an overview of the methodologies used in research. Last, to identify the gap in knowledge and to make recommendations for future work.Methods for the systematic reviewPopulation, Exposure, Control, Outcome and Study design (PECOS) criteria were used in developing the review questions. The review protocol follows the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and was pre-registered in the Prospective Register of Systematic Reviews (PROSPERO; CRD42020201480). Data Sources: EMBASE, PubMed, MEDLINE (Ovid), PsycINFO, ComDisDome, CINAHL, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL) via Cochrane Library, and scanning reference lists of relevant studies, and internet resources (i.e., Mendeley) were used. Only studies published between 1999 and 2022, in English, or in English translation, were included. The quality of evidence was assessed using the Newcastle-Ottawa Scale (NOS).ResultsSex differences: Women had more sensitive hearing (measured at the level of peripheral and central auditory system) than men. Cyclic fluctuations: Auditory function in women fluctuated during the menstrual cycle, while no such fluctuations in men over the same time period were reported. Hearing sensitivity improved in women during the late follicular phase, and decrease during the luteal phase, implying an effect of female sex hormones, although the specific effects of estradiol and progesterone fluctuations on the central auditory system remain unclear. Hearing sensitivity in women declined rapidly at the onset of menopause.ConclusionThe review has shown the following. Consistent sex differences exist in auditory function across the auditory pathway with pre-menopausal women often showing better function than age-matched men. Moreover, pre-menopausal women show fluctuations in hearing function across the menstrual cycle with a better function during the peak of estradiol or when the ratio of estradiol to progesterone is high. Third, menopause marks the onset of hearing loss in women, characterized by a rapid decline in hearing sensitivity and a more pronounced loss than in age-matched men. Finally, the systematic review highlights the need for well-designed and -controlled studies to evaluate the influence of estradiol and progesterone on hearing by consistently including control groups (e.g., age-matched man), using objective tests to measure hormonal levels (e.g., in saliva or blood), and by testing participants at different points across the menstrual cycle.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020201480, identifier CRD42020201480.