Search

Fatty acid‐binding protein 7 (FABP7), one of the fatty acid (FA) chaperones involved in the modulation of intracellular FA metabolism, is highly expressed in glioblastoma, and its expression is associated with decreased patients' prognosis. Previously, we demonstrated that FABP7 requires its binding partner to exert its function and that a mutation in the FA‐binding site of FABP7 affects tumour biology. Here, we explored the role of FA ligand binding for FABP7 function in tumour proliferation and examined the mechanism of FABP7 and ligand interaction in tumour biology. We discovered that among several FA treatment, oleic acid (OA) boosted cell proliferation of FABP7‐expressing cells. In turn, OA increased FABP7 nuclear localization, and the accumulation of FABP7–OA complex in the nucleus induced the formation of nuclear lipid droplet (nLD), as well as an increase in colocalization of nLD with promyelocytic leukaemia (PML) nuclear bodies. Furthermore, OA increased mRNA levels of proliferation‐related genes in FABP7‐expressing cells through histone acetylation. Interestingly, these OA‐boosted functions were abrogated in FABP7‐knockout cells and mutant FABP7‐overexpressing cells. Thus, our findings suggest that FABP7–OA intracellular interaction may modulate nLD formation and the epigenetic status thereby enhancing transcription of proliferation‐regulating genes, ultimately driving tumour cell proliferation. [ABSTRACT FROM AUTHOR]

Objective: To elucidate the association of glomerular filtration rate (GFR) at baseline with subsequent progression of albuminuria in individuals with type 2 diabetes.Research Design and Methods: This was a single-center retrospective cohort study of 6,618 Japanese adults with type 2 diabetes and urinary albumin-to-creatinine ratio of <300 mg/g, comprising 2,459 women and 4,159 men with a mean (± SD) age of 60 ± 12 years. The exposure was baseline estimated GFR (eGFR) (mL/min/1.73 m2), treated as a categorical variable and classified into five categories: ≥90, 75-90, 60-75, 45-60, and <45, as well as a continuous variable. The outcome was progression of albuminuria category (i.e., from normoalbuminuria to micro- or macroalbuminuria or from micro- to macroalbuminuria). Hazard ratios (HRs) for the outcome were estimated using the multivariable Cox proportional hazards model. In the analysis treating baseline eGFR as a continuous variable, the multivariable-adjusted restricted cubic spline model was used.Results: During the median follow-up period of 6.3 years, 1,190 individuals reached the outcome. When those with a baseline eGFR of 75-90 mL/min/1.73 m2 were considered the reference group, HRs (95% CIs) for the outcome in those with a baseline eGFR of ≥90, 60-75, 45-60, or <45 mL/min/1.73 m2 were 1.38 (1.14-1.66), 1.34 (1.14-1.58), 1.81 (1.50-2.20), or 2.37 (1.84-3.05), respectively. Furthermore, the inverse J-shaped curve was more clearly shown by the spline model.Conclusions: This study of Japanese adults with type 2 diabetes suggests that both high and low GFRs are implicated in the pathogenesis of albuminuria progression.Article Highlights: Glomerular hyperfiltration may induce kidney damage. We asked whether glomerular filtration rate (GFR) is associated with subsequent development and progression of albuminuria in people with diabetes. This retrospective cohort study of 6,618 adults with type 2 diabetes has shown that both an estimated GFR (eGFR) ≥90 mL/min/1.73m2 and an eGFR <75 mL/min/1.73m2 at baseline were risk factors for the subsequent category progression of albuminuria. This study suggests that both a high and low GFR are implicated in the pathogenesis of albuminuria development and progression in people with diabetes. [ABSTRACT FROM AUTHOR]

Plasmacytoid dendritic cells (pDCs) promote viral elimination by producing large amounts of Type I interferon. Recent studies have shown that pDCs regulate the pathogenesis of diverse inflammatory diseases, such as cancer. Fatty acid‐binding protein 5 (FABP5) is a cellular chaperone of long‐chain fatty acids that induce biological responses. Although the effects of FABP‐mediated lipid metabolism are well studied in various immune cells, its role in pDCs remains unclear. This study, which compares wild‐type and Fabp5−/− mice, provides the first evidence that FABP5‐mediated lipid metabolism regulates the commitment of pDCs to inflammatory vs tolerogenic gene expression patterns in the tumor microenvironment and in response to toll‐like receptor stimulation. Additionally, we demonstrated that FABP5 deficiency in pDCs affects the surrounding cellular environment, and that FABP5 expression in pDCs supports the appropriate generation of regulatory T cells (Tregs). Collectively, our findings reveal that pDC FABP5 acts as an important regulator of tumor immunity by controlling lipid metabolism. What's new? Regulatory T cells (Tregs) obstruct antitumour immunity, promoting tumour microenvironment formation. Although plasmacytoid DCs (pDCs) are pivotal Treg inducers, the effects of FABP5‐mediated lipid homeostasis in pDCs on Tregs remain unclear. This study suggests that FABP5‐mediated lipid metabolism regulates the commitment of pDCs to inflammatory versus tolerogenic gene expression patterns in the tumour microenvironment. Furthermore, FABP5 deficiency in mice attenuated tumour progression and decreased the tumour microenvironment Treg population. Loss of FABP5 from pDCs also impaired Treg induction. The findings suggest that pDC FABP5 acts as an important regulator of tumour immunity by controlling lipid metabolism. [ABSTRACT FROM AUTHOR]