Early macrophage response to obesity encompasses Interferon Regulatory Factor 5 regulated mitochondrial architecture remodelling.

Adipose tissue macrophages (ATM) adapt to changes in their energetic microenvironment. Caloric excess, in a range from transient to diet-induced obesity, could result in the transition of ATMs from highly oxidative and protective to highly inflammatory and metabolically deleterious. Here, we demonstrate that Interferon Regulatory Factor 5 (IRF5) is a key regulator of macrophage oxidative capacity in response to caloric excess. ATMs from mice with genetic-deficiency of Irf5 are characterised by increased oxidative respiration and mitochondrial membrane potential. Transient inhibition of IRF5 activity leads to a similar respiratory phenotype as genomic deletion, and is reversible by reconstitution of IRF5 expression. We find that the highly oxidative nature of Irf5-deficient macrophages results from transcriptional de-repression of the mitochondrial matrix component Growth Hormone Inducible Transmembrane Protein (GHITM) gene. The Irf5-deficiency-associated high oxygen consumption could be alleviated by experimental suppression of Ghitm expression. ATMs and monocytes from patients with obesity or with type-2 diabetes retain the reciprocal regulatory relationship between Irf5 and Ghitm. Thus, our study provides insights into the mechanism of how the inflammatory transcription factor IRF5 controls physiological adaptation to diet-induced obesity via regulating mitochondrial architecture in macrophages.

Anaemia and its risk factors and association with treatments in patients with diabetes: A cross-sectional study.

BACKGROUND: Anaemia is frequently seen in patients with diabetes and the main cause is renal failure. At all stages of renal failure, however, the prevalence of anaemia is higher in diabetes patients than expected for their glomerular filtration rate, suggesting that causes of anaemia other than renal failure are at work. The present cross-sectional study was conducted to investigate the possible iatrogenic causes of anaemia in patients with diabetes. SUBJECTS AND METHODS: This was a hospital-based cross-sectional study of all patients who had biological and clinical data covering a 2-year period. All had been in contact with the diabetes department either as outpatients or as inpatients mostly for educational purposes. Clinical factors, including type of diabetes, known diabetes complications, treatments received and biological data, were reviewed for their possible involvement in anaemia. RESULTS: A total of 4145 consecutive patients were included. Anaemia was observed in 1065 (25.7%) of them. Patients with anaemia were more frequently women and those with longer durations of diabetes. Haemoglobin concentrations were decreased, and prevalence of anaemia was increased at all stages of renal failure, already at stage 2, KDIGO classification. Anaemia patients were more frequently taking insulin, antiplatelet agents and renin-angiotensin system blockers (RASBs). After exclusion of patients with specific causes of anaemia, logistic regression analysis of all parameters correlated with anaemia on univariate analysis revealed that anaemia was associated with gender, antiplatelet agents and RASBs. CONCLUSION: This study has confirmed that anaemia is frequently seen in diabetes patients and strongly associated with renal failure (already at stage 2). Our observations highlight the adjuvant role of drugs, particularly RASBs, in the risk of anaemia in patients with diabetes.