Schlaepfer, J. | Search bioRxiv

bioRxiv2026

Depletion of astrocyte inflammatory pathway in the arcuate nucleus of the hypothalamus is sufficient to prevent the diet-induced metabolic alterations of polygenically predisposed obese rats

Selectively bred diet-induced obesity-prone (DIO-P) rats have defective nutrient sensing prior to obesity onset. We hypothesized that glial inflammation in the arcuate nucleus (ARC) impairs hypothalamic responses to dietary clues, thereby promoting obesity development in genetically susceptible animals. This study established a timeline of inflammatory events in male and female DIO-P and diet-resistant (DR) rats fed either a low fat chow or exposed to a high energy diet (HED; 32% fat, 25% sucrose) for three days or four weeks. On chow diet, DIO-P rats of both sexes displayed elevated astrocyte density and increased expression of pro-inflammatory markers in the ARC, alongside reduced microglial content, compared to DR rats. Three days of HED transiently amplified most MBH pro-inflammatory markers in DIO-P rats. Four weeks of HED decreased GFAP expression in DIO-P rats while Iba1 density remained unchanged, whereas, DR rats showed a reduction in Iba1with no change in GFAP or cytokine expression. To determine whether mediobasal hypothalamus (MBH) astrocyte inflammation contributes to the development and maintenance of an obesity, astrocytic IKK{beta} was depleted before or after HED exposure. Prophylactic MBH astrocyte-specific IKK{beta} knockdown prevented subsequent body weight gain, improved glucose tolerance and decreased leptin levels in DIO-P rats to levels comparable to DR rats, with no effect in the latter. In contrast, MBH IKK{beta} astrocytic depletion in already obese DIO-P rats had no effect on energy homeostasis. Together, these findings validate the DIO-P rat as a polygenic model of obesity predisposition and demonstrate that preventing ARC astrogliosis is sufficient to HED-induced body weight gain and obesity development in genetically susceptible animals, highlighting MBH inflammation as a marker and driver of obesity predisposition. HighlightsO_LIChow-fed DIO-P rats present heightened ARC astrogliosis and cytokine expression preceding HED-induced obesity. C_LIO_LIInhibition of IKK{beta} in MBH astrocytes prevents DIO-P rats from becoming obese. C_LIO_LIOnce obese, inhibition of IKK{beta} in MBH astrocytes is not sufficient to reverse the obese phenotype. C_LI

physiology↗

bioRxiv2026

Paralleled Dynamics of Arabidopsis Root Exudation and SynCom Assembly in a Controlled Environment

Plant roots host defined microbial communities that differ from those found in the surrounding soil and these communities shift dynamically in response to plant development and environmental changes. Whilst it is widely accepted that root exudates play a key role in the assembly and dynamics of root-associated microbial communities, the underlying mechanisms are not well understood. This is partly due to a lack of controlled experimental systems that monitor both exudate- and microbiome-dynamics simultaneously. Here, we compared two microcosm systems commonly used in either root microbiome (clay particle-based) or root exudate studies (glass bead-based) for their suitability to simultaneously monitor both aspects. We evaluated these systems based on plant performance, bacterial growth, and time-resolved community and exudate profiling. In both systems, we reveal an exudate effect, characterised by higher bacterial diversity and Pseudomonas abundances in proximity to plant roots. While clay particles impeded exudate recovery, even when plants were removed from microcosms for exudate collection, the glass bead set-up allowed us to uncover dynamic exudate shifts during bacterial community establishment. This highlighted a transient increase of glucosinolates upon root colonisation by initially dominant Pseudomonas species. Overall, the comparison proved only the glass bead-based semi-hydroponic system to be suitable for the paralleled study of exudate and root microbiome dynamics.

plant biology↗