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[¹⁸F]F-AraG imaging reveals association between neuroinflammation and brown- and bone marrow adipose tissue.

ABSTRACT: Brown and brown-like adipose tissues have attracted significant attention for their role in metabolism and therapeutic potential in diabetes and obesity. Despite compelling evidence of an interplay between adipocytes and lymphocytes, the involvement of these tissues in immune responses remains largely unexplored. This study explicates a newfound connection between neuroinflammation and brown- and bone marrow adipose tissue. Leveraging the use of [¹⁸F]F-AraG, a mitochondrial metabolic tracer capable of tracking activated lymphocytes and adipocytes simultaneously, we demonstrate, in models of glioblastoma and multiple sclerosis, the correlation between intracerebral immune infiltration and changes in brown- and bone marrow adipose tissue. Significantly, we show initial evidence that a neuroinflammation-adipose tissue link may also exist in humans. This study proposes the concept of an intricate immuno-neuro-adipose circuit, and highlights brown- and bone marrow adipose tissue as an intermediary in the communication between the immune and nervous systems. Understanding the interconnectedness within this circuitry may lead to advancements in the treatment and management of various conditions, including cancer, neurodegenerative diseases and metabolic disorders.

SUBMITTER: Levi J

PROVIDER: S-EPMC11217368 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature

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[<sup>18</sup>F]F-AraG imaging reveals association between neuroinflammation and brown- and bone marrow adipose tissue.

Levi Jelena J Guglielmetti Caroline C Henrich Timothy J TJ Yoon John C JC Gokhale Prafulla C PC Reardon David A DA Packiasamy Juliet J Huynh Lyna L Cabrera Hilda H Ruzevich Marisa M Blecha Joseph J Peluso Michael J MJ Huynh Tony L TL An Sung-Min SM Dornan Mark M Belanger Anthony P AP Nguyen Quang-Dé QD Seo Youngho Y Song Hong H Chaumeil Myriam M MM VanBrocklin Henry F HF Chae Hee-Don HD

Communications biology 20240701 1

Brown and brown-like adipose tissues have attracted significant attention for their role in metabolism and therapeutic potential in diabetes and obesity. Despite compelling evidence of an interplay between adipocytes and lymphocytes, the involvement of these tissues in immune responses remains largely unexplored. This study explicates a newfound connection between neuroinflammation and brown- and bone marrow adipose tissue. Leveraging the use of [<sup>18</sup>F]F-AraG, a mitochondrial metabolic ...[more]

PMID: 38951146

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Project description:BackgroundBrown adipose tissue (BAT) is a thermogenic tissue which can generate heat in response to mild cold exposure. As it constitutes a promising target in the fight against obesity, we need reliable techniques to quantify its activity in response to therapeutic interventions. The current standard for the quantification of BAT activity is [18F]FDG PET/CT. Various sequences in magnetic resonance imaging (MRI), including those measuring its relative fat content (fat fraction), have been proposed and evaluated in small proof-of-principle studies, showing diverging results. Here, we systematically compare the predictive value of adipose tissue fat fraction measured by MRI to the results of [18F]FDG PET/CT.MethodsWe analyzed the diagnostic reliability of MRI measured fat fraction (FF) for the estimation of human BAT activity in two cohorts of healthy volunteers participating in two prospective clinical trials (NCT03189511, NCT03269747). In both cohorts, BAT activity was stimulated by mild cold exposure. In cohort 1, we performed [18F]FDG PET/MRI; in cohort 2, we used [18F]FDG PET/CT followed by MRI. Fat fraction was determined by 2-point Dixon and 6-point Dixon measurement, respectively. Fat fraction values were compared to SUVmean in the corresponding tissue depot by simple linear regression.ResultsIn total, 33 male participants with a mean age of 23.9 years and a mean BMI of 22.8 kg/m2 were recruited. In 32 participants, active BAT was visible. On an intra-individual level, FF was significantly lower in high-SUV areas compared to low-SUV areas (cohort 1: p < 0.0001 and cohort 2: p = 0.0002). The FF of the supraclavicular adipose tissue depot was inversely related to its metabolic activity (SUVmean) in both cohorts (cohort 1: R2 = 0.18, p = 0.09 and cohort 2: R2 = 0.42, p = 0.009).ConclusionMRI FF explains only about 40% of the variation in BAT glucose uptake. Thus, it can currently not be used to substitute [18F] FDG PET-based imaging for quantification of BAT activity.Trial registrationClinicalTrials.gov. NCT03189511 , registered on June 17, 2017, actual study start date was on May 31, 2017, retrospectively registered. NCT03269747 , registered on September 01, 2017.

Project description:Browning of white adipose tissue (WAT) into beige adipocytes has been proposed as a strategy to tackle the ongoing obesity epidemic. Thermogenic stimuli have been investigated with the aim of converting existing white adipose tissue, primarily used for energy storage, into beige adipocytes capable of dissipating energy; however, evaluation is complicated by the dearth of noninvasive methodologies to quantify de novo beige adipocytes in WAT. Imaging with [18F]FDG is commonly used to measure brown adipose tissue (BAT) and beige adipocytes but the relationship between beige adipocytes, thermogenesis and [18F]FDG uptake is unclear. [18F]BCPP-EF, a tracer for mitochondrial complex-I (MC-I), acts as a marker of oxidative metabolism and may be useful for the detection of newly formed beige adipocytes. Mice received doses of the β3-adrenergic agonist CL-316,243 subchronically for 7 days to induce formation of beige adipocytes in inguinal white fat. PET imaging was performed longitudinally with both [18F]FDG (a marker of glycolysis) and [18F]BCPP-EF (an MC-I marker) to assess the effect of thermogenic stimulation on uptake in browning inguinal WAT and interscapular BAT. Treatment with CL-316,243 led to significant increases in both [18F]FDG and [18F]BCPP-EF in inguinal WAT. The uptake of [18F]BCPP-EF in inguinal WAT was significantly increased above control levels after 3 days of stimulation, whereas [18F]FDG only showed a significant increase after 7 days. The uptake of [18F]BCPP-EF in newly formed beige adipocytes was blocked by pretreatment with an adrenoceptor antagonist suggesting that beige adipocyte formation may be associated with the activation of MC-I. However, in BAT, uptake of [18F]BCPP-EF was unaffected by β3-adrenergic stimulation, potentially due to the high expression of MC-I. [18F]BCPP-EF can detect newly formed beige adipocytes in WAT generated after subchronic treatment with the β3-adrenergic agonist CL-316,243 and displays both higher inguinal WAT uptake and earlier detection than [18F]FDG. The MC-I tracer may be a useful tool in the evaluation of new therapeutic strategies targeting metabolic adipose tissues to tackle obesity and metabolic diseases.

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[¹⁸F]F-AraG imaging reveals association between neuroinflammation and brown- and bone marrow adipose tissue.

Publications

[<sup>18</sup>F]F-AraG imaging reveals association between neuroinflammation and brown- and bone marrow adipose tissue.

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[18F]F-AraG imaging reveals association between neuroinflammation and brown- and bone marrow adipose tissue.

Publications

[<sup>18</sup>F]F-AraG imaging reveals association between neuroinflammation and brown- and bone marrow adipose tissue.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

[¹⁸F]F-AraG imaging reveals association between neuroinflammation and brown- and bone marrow adipose tissue.