Roy Rasalam

Short-chain fatty acids increase expression and secretion of stromal cell-derived factor-1 in mouse and human pre-adipocytes

OBJECTIVEStromal cell-derived factor-1 (SDF-1) is expressed in pre-adipocytes but its role is unknown. We investigated butyrate (a histone deacetylase inhibitor — HDACi) and other short-chain fatty acids (SCFA) in the regulation of SDF-1. We further investigated whether effects of SCFA were signalled through G protein-coupled receptors FFA2 and FFA3.DESIGN AND RESULTSSDF-1 mRNA expression and protein secretion were studied in 3T3-L1 cells and human pre-adipocytes. SDF-1 was abundant, with mRNA and protein levels increased by butyrate. This was replicated with acetate and propionate, but not with trichostatin or valproate. Trichostatin inhibited SDF-1 secretion. Pertussis toxin blocked stimulation by butyrate. The order of potency of SCFA in stimulating SDF-1 (C3 > C4 > C2) is consistent with action through FFA3. Silencing the FFA3 gene abolished butyrate-stimulated SDF-1 expression and secretion. FFA3 was expressed in both pre-adipocytes and adipocytes, while FFA2 was expressed in adipocytes only. SDF-1 expression was low in murine macrophage J774.2 cells, while the SDF-1 receptor CXCR4 was absent from 3T3-L1 cells but abundant in J774.2 macrophages. In human pre-adipocytes, FFA3 was also expressed and SCFA increased SDF-1 secretion.CONCLUSIONSSDF-1 and CXCR4 may mediate the interaction between adipose stromal cells and macrophages. Effects of SCFA are mediated through FFA3, but not histone deacetylase inhibition.

Growth of the James Cook University medical program: maintaining quality, continuing the vision, developing postgraduate pathways

Abstract Background: James Cook University (JCU) enrolled its first cohort of 64 in 2000 into a 6-year undergraduate medical program aimed at producing graduates capable of meeting the needs of North Queensland, Australia, with a focus on rural, remote, Indigenous and tropical health. The school’s 1465 graduates over 13 cohorts who have a pattern of practice likely to meet the region’s health needs. The JCU course was the first new Australian medical program for 25 years. The number of Australian medical schools has since doubled, while enrollments have almost tripled. Methods: JCU’s course features innovations such as dispersed, community-based education, rurally-focused selection, extended rural placements, and an emphasis on community needs – which are all now mainstream. This paper traces developments at JCU over the past decade, illustrating parallels with the broader Australian scene. Results: Maintaining quality and educational integrity while numbers grow is challenging. The course has undergone modest curriculum redesign, but the fundamental elements are intact. The focus on meeting the region’s needs remains, with some evolution of its mission to include social accountability and the needs of underserved populations. Conclusions: Postgraduate pathways are an important priority. Regional training hubs are being developed to support local pipelines into specialty practice. Queensland’s Rural Generalist Pathway provides an incentivised pathway to rural practice while Generalist Medical Training provides a local training pipeline into general practice and rural medicine. As these initiatives mature, communities should benefit as JCU and other Australian programs continue to address local workforce needs.