Biology subjects

Ohue-Kitano, R.

Publications and source records attributed to Ohue-Kitano, R..

3 recordsLinked to original sources

bioRxiv2026

Maternal progesterone signaling establishes lifelong oral homeostasis

Pregnancy is accompanied by profound endocrine remodeling, yet the mechanisms by which maternal hormonal signals establish long-term tissue homeostasis remain largely unknown. Here we identify maternal progesterone signaling as a developmental cue that establishes lifelong oral homeostasis through a hormone-lipid-microbiome axis. We show that the membrane progesterone receptor mPR{delta} is selectively expressed in the developing and maternal submandibular glands, where it mediates non-genomic progesterone signaling to promote epithelial differentiation by driving the selective mobilization of docosahexaenoic acid (DHA). Loss of this pathway disrupts salivary gland maturation, reshapes the oral microbial ecosystem through the selective expansion of Pasteurellaceae, and causes local inflammation as well as systemic metabolic dysfunction. Mechanistically, antibiotic treatment abolishes these phenotypes, whereas transfer of the oral microbiota recapitulates disease, demonstrating that developmental defects in the host are translated into long-term pathology through the oral microbiome. Remarkably, maternal--but not adult--DHA supplementation restores salivary gland development and microbial homeostasis and prevents adult disease phenotypes, identifying a critical developmental window during which oral homeostasis is durably established. Collectively, these findings reveal a previously unrecognized maternal endocrine mechanism that establishes lifelong host-microbiome homeostasis and identify developmental programming as a fundamental principle linking maternal physiology to adult health. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=188 SRC="FIGDIR/small/743932v1_ufig1.gif" ALT="Figure 1"> View larger version (56K): org.highwire.dtl.DTLVardef@178cc90org.highwire.dtl.DTLVardef@1be04beorg.highwire.dtl.DTLVardef@29759dorg.highwire.dtl.DTLVardef@1e89994_HPS_FORMAT_FIGEXP M_FIG C_FIG

physiology↗

bioRxiv2025

Ketone-body receptor GPR109A suppresses hepatic inflammation via gut-liver axis regulation

The ketogenic diet (KD) promotes ketone body synthesis and has been used as an effective treatment for disorders such as epilepsy. Although elevated ketone bodies, including {beta}-hydroxybutyrate ({beta}HB) and acetoacetate, are thought to meditate the beneficial effects of the KD, the mechanisms underlying their metabolic actions remain incompletely understood. In this study, we focused on GPR109A, a receptor for {beta}HB with an unclear role in metabolic homeostasis. We employed KD and fasting models to examine metabolic changes under two distinct ketogenic conditions. Under KD conditions, Gpr109a-/- mice exhibited increased hepatic lipid accumulation, and subsequent hepatic inflammation and fibrosis. However, Gpr109a deletion did not exacerbate hepatic lipid accumulation or inflammation during short-term fasting, suggesting that GPR109A-mediated liver protection is specific to KD-induced metabolic stress rather than under fasting conditions. Mechanistic analysis revealed that GPR109A protects the liver from inflammation by maintaining intestinal barrier integrity. These findings highlight the novel protective mechanism of GPR109A, via the gut-liver axis, to sustain metabolic homeostasis during the KD. This study provides valuable insights into the physiological effects of ketone bodies.

physiology↗

bioRxiv2024

Maternal progesterone and adipose mPRε in pregnancy regulate the embryonic nutritional state

Sex steroid hormones such as progesterone play a pivotal role in reproductive functions and maintaining pregnancy; however, the impact of progesterone on the interaction between mother and embryo is unclear. Here, we demonstrate that the relationship between maternal progesterone and membrane progesterone receptor epsilon (mPR{varepsilon}) in adipose tissue regulates embryonic nutritional environment and growth after birth in mice. The activation of adipose mPR{varepsilon} by increased progesterone during pregnancy enhanced maternal insulin resistance through the production of prostaglandins, thereby efficiently providing glucose to embryos. The offspring of mPR{varepsilon}-deficient mothers exhibited metabolic dysfunction, whereas mPR{varepsilon}-deficient mothers with high-fat-diet-induced obesity exhibited improved insulin sensitivity. These findings establish the importance of progesterone as a nutritional regulator between mother and embryo, and suggest that mPR{varepsilon} modulators could be developed to treat pregnant glycemic control disorders such as gestational diabetes mellitus, as well as metabolic syndrome in offspring. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=139 SRC="FIGDIR/small/609823v1_ufig1.gif" ALT="Figure 1"> View larger version (29K): org.highwire.dtl.DTLVardef@1ecd968org.highwire.dtl.DTLVardef@b5492aorg.highwire.dtl.DTLVardef@1d692ecorg.highwire.dtl.DTLVardef@47de8a_HPS_FORMAT_FIGEXP M_FIG C_FIG

physiology↗