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Homo and heterozygote cx3cr1 mutant mice, which harbor a green fluorescent protein (EGFP) in their cx3cr1 loci, represent a widely used animal model to study microglia and peripheral myeloid cells. Here we report that microglia in the dentate gyrus (DG) of cx3cr1−/− mice displayed elevated microglial sirtuin 1 (SIRT1) expression levels and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) p65 activation, despite unaltered morphology when compared to cx3cr1+/− or cx3cr1+/+ controls. This phenotype was restricted to the DG and accompanied by reduced adult neurogenesis in cx3cr1−/− mice. Remarkably, adult neurogenesis was not affected by the lack of the CX3CR1-ligand, fractalkine (CX3CL1). Mechanistically, pharmacological activation of SIRT1 improved adult neurogenesis in the DG together with an enhanced performance of cx3cr1−/− mice in a hippocampus-dependent learning and memory task. The reverse condition was induced when SIRT1 was inhibited in cx3cr1−/− mice, causing reduced adult neurogenesis and lowered hippocampal cognitive abilities. In conclusion, our data indicate that deletion of CX3CR1 from microglia under resting conditions modifies brain areas with elevated cellular turnover independent of CX3CL1.

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VAT and VAT/SAT ratio are associated with impaired glucose metabolism, independent of cardiovascular risk factors or MRI-based quantification technique, with a decreasing effect of VAT/SAT ratio in obese subjects. Advances in knowledge: Quantification of VAT and VAT/SAT ratio by MRI represents a reproducable biomarker associated with cardiometabolic risk factors in subjects with impaired glucose metabolism, while the association of VAT/SAT ratio with glycemic state is attenuated in obese subjects.

Objectives Prior studies relating body mass index (BMI) to brain volumes suggest an overall inverse association. However, BMI might not be an ideal marker, as it disregards different fat compartments, which carry different metabolic risks. Therefore, we analyzed MR-based fat depots and their association with gray matter (GM) volumes of brain structures, which show volumetric changes in neurodegenerative diseases. Methods Warp-based automated brain segmentation of 3D FLAIR sequences was obtained in a population-based study cohort. Associations of temporal lobe, cingulate gyrus, and hippocampus GM volume with BMI and MR-based quantification of visceral adipose tissue (VAT), as well as hepatic and pancreatic proton density fat fraction (PDFF hepatic and PDFF panc , respectively), were assessed by linear regression. Results In a sample of 152 women (age 56.2 ± 9.0 years) and 199 men (age 56.1 ± 9.1 years), we observed a significant inverse association of PDFF hepatic and cingulate gyrus volume (p < 0.05) as well as of PDFF hepatic and hippocampus volume (p < 0.05), when adjusting for age and sex. This inverse association was further enhanced for cingulate gyrus volume after additionally adjusting for hypertension, smoking, BMI, LDL, and total cholesterol (p < 0.01) and also alcohol (p < 0.01). No significant association was observed between PDFF hepatic and temporal lobe and between temporal lobe, cingulate gyrus, or hippocampus volume and BMI, VAT, and PDFF panc . Conclusions We observed a significant inverse, independent association of cingulate gyrus and hippocampus GM volume with hepatic fat, but not with other obesity measures. Increased hepatic fat could therefore serve as a marker of high-risk fat distribution. Key Points• Obesity is associated with neurodegenerative processes.• In a population-based study cohort, hepatic fat was superior to BMI and visceral and pancreatic fat as a risk biomarker for decreased brain volume of cingulate gyrus and hippocampus. • Increased hepatic fat could serve as a marker of high-risk fat distribution.