Biology subjects

Rogner, U. C.

Publications and source records attributed to Rogner, U. C..

2 recordsLinked to original sources

bioRxiv2025

BMAL2 controls adipose tissue inflammation and metabolic adaptation during obesity

Contemporary lifestyle modifications such as changes in nutritional and sleep/wake rhythms increase the risk of metabolic and inflammatory complications linked to obesity, including type 2 diabetes (T2D) and metabolic dysfunction-associated steatohepatitis (MASH). BMAL2 (Brain and Muscle ARNT Like Protein 2) is a transcription factor belonging to the circadian clock transcriptional feedback loop which synchronizes internal biological rhythms to environment. In humans, reduced expression in white adipose tissue (WAT) and specific polymorphisms of BMAL2 are associated with obesity and T2D. In this study we report that Bmal2 invalidation in mice leads to increased body weight gain during diet-induced obesity. Loss of BMAL2 triggers the inflammatory response by increasing Tnf expression and modifying adipocyte progenitor fate. This results in reduced lipid storage capacity within the WAT and increased ectopic storage in the liver. These functional and structural alterations culminate in the onset of hepatic steatosis and insulin resistance in liver and WAT. Overall, our investigations underscore the role of BMAL2 in the development and function of adipocytes, as well as in their inflammatory potential within the WAT. Our findings contribute to the understanding of the role of circadian clock genes in obesity and interconnected metabolic complications. HighlightsO_LIThe transcription factor BMAL2 is involved in metabolic complications of obesity in a mouse model of diet-induced obesity C_LIO_LIInvalidation of Bmal2 worsens insulin resistance and hepatic steatosis induced by high fat diet C_LIO_LIInvalidation of Bmal2 impairs visceral adipose tissue adaptation capacity in promoting inflammation and adipose progenitor decline C_LI Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=198 HEIGHT=200 SRC="FIGDIR/small/641984v1_ufig1.gif" ALT="Figure 1"> View larger version (29K): org.highwire.dtl.DTLVardef@1d60e1eorg.highwire.dtl.DTLVardef@38daaaorg.highwire.dtl.DTLVardef@9c0040org.highwire.dtl.DTLVardef@1d484bb_HPS_FORMAT_FIGEXP M_FIG C_FIG

pathology↗

bioRxiv2023

Differential action of TIGIT on islet and peripheral nerve autoimmunity in the NOD mouse

We previously demonstrated that the abrogation of the ICOS pathway prevents type 1 diabetes development in the Non Obese Diabetic (NOD) mouse, but results in a CD4+ T-cell dependent autoimmune neuromyopathy in aged mice. Pancreatic islet infiltrates in conventional NOD mice and neuromuscular infiltrates in Icosl-/- NOD mice have in common that they exhibit a strong enrichment in CD4+TIGIT+ T-cells, whilst TIGIT expression in the peripheral CD4+ T-cells is limited to the CD4+FoxP3+ T-cell population. When deleting Tigit on the NOD background, diabetes incidence was found increased. Peripheral CD4+CD226+ effector T-cells exhibited an increased frequency of IL-17 producing CD4+CD226+RORgt+ T-cells versus a decreased frequency of IFN{gamma}-producing CD4+CD226+Tbet+ T-cells. ICOS is expressed in both CD4+FoxP3+ and CD4+CD226+ splenic T-cell subsets. Icosl deletion leads to a decrease of CD4+FoxP3+ cells, with decrease of PD1 but increase of ICOS and CCRX3. Also in the Icosl-/- model, CD4+CD226+ T-cells are decreased by Tigit deletion, and showed an increase of CD4+CD226+RORgt+ T-cells and a decrease of CD4+CD226+Tbet+ T-cells. However, deletion of Tigit in aged Icosl-/-NOD mice population did not increase the incidence of the autoimmune neuromyopathy observed in Icosl-/-NOD mice. Interestingly, the upregulation of CD4+CD226+RORgt+ T-cells was partly rescued. We conclude from our study that both Icosl and Tigit deletions on the NOD background lead to a shift between the ratio of IFN{gamma} and IL-17-producing CD4+CD226+ effector cells. The ICOS-dependent neuromyopathy development remains dominant and is not further altered in the absence of TIGIT. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=132 SRC="FIGDIR/small/568543v1_ufig1.gif" ALT="Figure 1"> View larger version (25K): org.highwire.dtl.DTLVardef@de7ba4org.highwire.dtl.DTLVardef@8756b0org.highwire.dtl.DTLVardef@14c4a6borg.highwire.dtl.DTLVardef@1a9cd02_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗