NUCB2/Nesfatin-1 Reduces Obesogenic Diet Induced Inflammation in Mice Subcutaneous White Adipose Tissue.

BACKGROUND: Excess adipose tissue accumulation and obesity are characterised by chronic, low-grade, systemic inflammation. Nestfatin-1 is a neuropeptide derived from the precursor protein nucleobindin-2 (NUCB2), which was initially reported to exert anorexigenic effects. The present study aimed to investigate the effects of an obesogenic diet (OD; high-fat, high-sugar) in NUCB2 knockout (KO) mice and of nesfatin-1 treatment in LPS-stimulated 3T3-L1 preadipocytes. METHODS: Subcutaneous white adipose tissue (Sc-WAT) samples from wild type (WT) and NUCB2 KO mice that were fed a normal diet (ND), or the OD for 12 weeks were used for RNA and protein extraction, as well as immunohistochemistry. 3T3-L1 cells were treated with 100 nM nesfatin-1 during differentiation and stimulated with 1 µg/mL LPS for measuring the expression and secretion of pro-inflammatory mediators by qPCR, western blotting, immunofluorescence, Bioplex, and ELISA. RESULTS: Following the OD, the mRNA, protein and cellular expression of pro-inflammatory mediators (Tnfα, Il-6, Il-1ß, Adgre1, Mcp1, TLR4, Hmbgb1 and NF-kB) significantly increased in the ScWAT of NUCB2 KO mice compared to ND controls. Adiponectin and Nrf2 expression significantly decreased in the ScWAT of OD-fed NUCB2 KO, without changes in the OD-fed WT mice. Furthermore, nesfatin-1 treatment in LPS-stimulated 3T3-L1 cells significantly reduced the expression and secretion of pro-inflammatory cytokines (Tnfα, Il-6, Il-1ß, Mcp1) and hmgb1. CONCLUSION: An obesogenic diet can induce significant inflammation in the ScWAT of NUCB2 KO mice, involving the HMGB1, NRF2 and NF-kB pathways, while nesfatin-1 reduces the pro-inflammatory response in LPS-stimulated 3T3-L1 cells. These findings provide a novel insight into the metabolic regulation of inflammation in WAT.

A Systematic Review to Assess the Impact of Hyperbaric Oxygen Therapy on Glycaemia in People with Diabetes Mellitus.

Background and Objectives: Hyperbaric oxygen is a recognised treatment for a range of medical conditions, including treatment of diabetic foot disease. A number of studies have reported an impact of hyperbaric oxygen treatment on glycaemic control in patients undergoing treatment for diabetic foot disease. There has been no systematic review considering the impact of hyperbaric oxygen on glycaemia in people with diabetes. Materials and Methods: A prospectively PROSPERO-registered (PROSPERO registration: CRD42021255528) systematic review of eligible studies published in English in the PUBMED, MEDLINE, and EMBASE databases, based on the following search terms: hyperbaric oxygen therapy, HBO2, hyperbaric oxygenation, glycaemic control, diabetes, diabetes Mellitus, diabetic, HbA1c. Data extraction to pre-determined piloted data collection form, with individual assessment of bias. Results: In total, 10 eligible publications were identified after screening. Of these, six articles reported a statistically significant reduction in blood glucose from hyperbaric oxygen treatment, while two articles reported a statistically significant increase in peripheral insulin sensitivity. Two articles also identified a statistically significant reduction in HbA1c following hyperbaric oxygen treatment. Conclusions: There is emerging evidence suggesting a reduction in glycaemia following hyperbaric oxygen treatment in patients with diabetes mellitus, but the existing studies are in relatively small cohorts and potentially underpowered. Additional large prospective clinical trials are required to understand the precise impact of hyperbaric oxygen treatment on glycaemia for people with diabetes mellitus.

FSH Requirements for Follicle Growth During Controlled Ovarian Stimulation.

Introduction: Ovarian follicle growth is a key step in the success of assisted reproductive treatment, but limited data exists to directly relate follicle growth to recombinant FSH (rFSH) dose. In this study, we aim to evaluate FSH requirements for follicular growth during controlled ovarian stimulation. Method: Single center retrospective cohort study of 1,034 IVF cycles conducted between January 2012-January 2016 at Hammersmith Hospital IVF unit, London, UK. Median follicle size after 5 days of stimulation with rFSH and the proportion of antral follicles recruited were analyzed in women treated with rFSH alone to induce follicular growth during IVF treatment. Results: Starting rFSH dose adjusted for body weight (iU/kg) predicted serum FSH level after 5 days of rFSH (r 2 = 0.352, p < 0.0001), median follicle size after 5 days of rFSH, and the proportion of antral follicles recruited by the end of stimulation. Day 5 median follicle size predicted median follicle size on subsequent ultrasound scans (r 2 = 0.58-0.62; p < 0.0001), and hence time to oocyte maturation trigger (r 2 = 0.22, P < 0.0001). Insufficient rFSH starting dose that required >5% dose-increase was associated with increased variability in follicle size on the day of oocyte maturation trigger, and negatively impacted the number of mature oocytes retrieved. Conclusion: Weight-adjusted rFSH dose correlates with follicular growth during ovarian stimulation. Early recruitment of follicles using a sufficient dose of rFSH from the start of stimulation was associated with reduced variability in follicle size at time of oocyte maturation trigger and an increased number of mature oocytes retrieved.