Phosphoprotein enriched in astrocytes (PEA)-15 is a novel regulator of adipose tissue expansion.

Excessive expansion of adipose tissue in obesity typically leads to overflow and accumulation of lipids in other tissues, causing fatty liver disease and atherosclerosis. The intracellular protein, phosphoprotein enriched in astrocytes (PEA)-15 has been linked to metabolic disease but its role in lipid storage has not been examined. To delineate the role of PEA-15 in adipose tissue, we placed PEA-15-/- mice on a high fat diet. These mice developed increased body weight and greater white adipose tissue expansion compared to high fat diet-fed wild type mice. This was due to increased adipocyte cell size in PEA-15-/- mice consistent with greater lipid storage capacity. Surprisingly, PEA-15-/- mice exhibited improvements in whole body insulin sensitivity, lower hepatic weight and decreased serum triglycerides indicating a protective phenotype. To determine effects on atherosclerosis, PEA-15-/- mice were crossed with the ApoE-/- mice on a high fat diet. Strikingly, these mice were protected from atherosclerosis and had less hepatic lipid accumulation despite increased adiposity. Therefore, we reveal for the first time that PEA-15 plays a novel role in regulating the expansion of adipose tissue. Decreasing PEA-15 expression increases the sequestering of lipids in adipose tissue, protecting other tissues in obesity, thereby improving metabolic health.

Prospective cohort study of water immersion for labour and birth compared with standard care in an Irish maternity setting.

OBJECTIVE: To examine the birth outcomes for women and babies following water immersion for labour only, or for labour and birth. DESIGN: Prospective cohort study. SETTING: Maternity hospital, Ireland, 2016-2019. PARTICIPANTS: A cohort of 190 low-risk women who used water immersion; 100 gave birth in water and 90 laboured only in water. A control group of 190 low-risk women who received standard care. METHODS: Logistic regression analyses examined associations between water immersion and birth outcomes adjusting for confounders. A validated Childbirth Experience Questionnaire was completed. MAIN OUTCOME MEASURES: Perineal tears, obstetric anal sphincter injuries (OASI), postpartum haemorrhage (PPH), neonatal unit admissions (NNU), breastfeeding and birth experiences. RESULTS: Compared with standard care, women who chose water immersion had no significant difference in perineal tears (71.4% vs 71.4%, adj OR 0.83; 95% CI 0.49 to 1.39) or in OASI (3.3% vs 3.8%, adj OR 0.91; 0.26-2.97). Women who chose water immersion were more likely to have a PPH ≥500 mL (10.5% vs 3.7%, adj OR 2.60; 95% CI 1.03 to 6.57), and to exclusively breastfeed at discharge (71.1% vs 45.8%, adj OR 2.59; 95% CI 1.66 to 4.05). There was no significant difference in NNU admissions (3.7% vs 3.2%, adj OR 1.06; 95% CI 0.33 to 3.42). Women who gave birth in water were no more likely than women who used water for labour only to require perineal suturing (64% vs 80.5%, adj OR 0.63; 95% CI 0.30 to 1.33), to experience OASI (3.0% vs 3.7%, adj OR 1.41; 95% CI 0.23 to 8.79) or PPH (8.0% vs 13.3%, adj OR 0.73; 95% CI 0.26 to 2.09). Women using water immersion reported more positive memories than women receiving standard care (p<0.01). CONCLUSIONS: Women choosing water immersion for labour or birth were no more likely to experience adverse birth outcomes than women receiving standard care and rated their birth experiences more highly.

Direct comparison of methionine restriction with leucine restriction on the metabolic health of C57BL/6J mice.

The effects of methionine restriction (MR) in rodents are well established; it leads to decreased body and fat mass, improved glucose homeostasis and extended lifespan, despite increased energy intake. Leucine restriction (LR) replicates some, but not all, of these effects of MR. To determine any differences in metabolic effects between MR and LR, this study compared 8 weeks of MR (80% restriction), LR (80% restriction) and control diet in 10-month-old C57BL/6J male mice. Body composition, food intake and glucose homeostasis were measured throughout the study and biochemical analyses of white adipose tissue (WAT) and liver were performed. MR and LR decreased body and fat mass, increased food intake, elevated lipid cycling in WAT and improved whole-body glucose metabolism and hepatic insulin sensitivity in comparison to the control diet. MR produced more substantial effects than LR on body mass and glucose homeostasis and reduced hepatic lipogenic gene expression, which was absent with the LR diet. This could be a result of amino acid-specific pathways in the liver responsible for FGF21 stimulation (causing varied levels of FGF21 induction) and Akt activation. In summary, LR is effective at improving metabolic health; however, MR produces stronger effects, suggesting they activate distinct signalling pathways.

Photoperiod- and Triiodothyronine-dependent Regulation of Reproductive Neuropeptides, Proinflammatory Cytokines, and Peripheral Physiology in Siberian Hamsters (Phodopus sungorus).

Seasonal trade-offs in reproduction and immunity are ubiquitous in nature. The mechanisms that govern transitions across seasonal physiological states appear to involve reciprocal switches in the local synthesis of thyroid hormone. In long-day (LD) summer-like conditions, increased hypothalamic triiodothyronine (T3) stimulates gonadal development. Alternatively, short-day (SD) winter-like conditions increase peripheral leukocytes and enhance multiple aspects of immune function. These data indicate that the localized effects of T3 in the hypothalamus and leukocytes are photoperiod dependent. We tested the hypothesis that increased peripheral T3 in SD conditions would increase aspects of reproductive physiology and inhibit immune function, whereas T3 injections in LD conditions would facilitate aspects of immune function (i.e., leukocytes). In addition, we also examined whether T3 regulates hypothalamic neuropeptide expression as well as hypothalamic and splenic proinflammatory cytokine expression. Adult male Siberian hamsters were maintained in LD (15L:9D) or transferred to SD (9L:15D) for 8 weeks. A subset of LD and SD hamsters was treated daily with 5 µg T3 for 2 weeks. LD and SD controls were injected with saline. Daily T3 administration in SD hamsters (SD+T3) resulted in a rapid and substantial decrease in peripheral leukocyte concentrations and stimulated gonadal development. T3 treatment in LD (LD+T3) had no effect on testicular volumes but significantly increased leukocyte concentrations. Molecular analyses revealed that T3 stimulated interleukin 1ß messenger RNA (mRNA) expression in the spleen and inhibited RFamide Related Peptide-3 mRNA expression in the hypothalamus. Moreover, there was a photoperiod-dependent decrease in splenic tumor necrosis factor-α mRNA expression. These findings reveal that T3 has tissue-specific and photoperiod-dependent regulation of seasonal rhythms in reproduction and immune function.

Vitamin E supplementation and mammalian lifespan.

Vitamin E refers to a family of several compounds that possess a similar chemical structure comprising a chromanol ring with a 16-carbon side chain. The degree of saturation of the side chain, and positions and nature of methyl groups designate the compounds as tocopherols or tocotrienols. Vitamin E compounds have antioxidant properties due to a hydroxyl group on the chromanol ring. Recently, it has been suggested that vitamin E may also regulate signal transduction and gene expression. We previously reported that lifelong dietary vitamin E (alpha-tocopherol) supplementation significantly increased median lifespan in C57BL/6 mice by 15%. This lifespan extension appeared to be independent of any antioxidant effect. Employing a transcriptional approach, we suggest that this increase in lifespan may reflect an anti-cancer effect via induction of the P21 signalling pathway, since cancer is the major cause of death in small rodents. We suggest that the role of this pathway in life span extension following supplementation of vitamin E now requires further investigation.