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Obesity results in adipose tissue T cell exhaustion.

ABSTRACT: Despite studies implicating adipose tissue T cells (ATT) in the initiation and persistence of adipose tissue inflammation, fundamental gaps in knowledge regarding ATT function impedes progress toward understanding how obesity influences adaptive immunity. We hypothesized that ATT activation and function would have tissue-resident-specific properties and that obesity would potentiate their inflammatory properties. We assessed ATT activation and inflammatory potential within mouse and human stromal vascular fraction (SVF). Surprisingly, murine and human ATTs from obese visceral white adipose tissue exhibited impaired inflammatory characteristics upon stimulation. Both environmental and cell-intrinsic factors are implicated in ATT dysfunction. Soluble factors from obese SVF inhibit ATT activation. Additionally, chronic signaling from macrophage major histocompatibility complex II (MHCII) is necessary for ATT impairment in obese adipose tissue but is independent of increased PD1 expression. To assess intracellular signaling mechanisms responsible for ATT inflammation impairments, single-cell RNA sequencing of ATTs was performed. ATTs in obese adipose tissue exhibit enrichment of genes characteristic of T cell exhaustion and increased expression of coinhibitory receptor Btla. In sum, this work suggests that obesity-induced ATTs have functional characteristics and gene expression resembling T cell exhaustion induced by local soluble factors and cell-to-cell interactions in adipose tissue.

SUBMITTER: Porsche CE

PROVIDER: S-EPMC8119198 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background/objectivesWeight loss outcomes vary individually. Magnetic resonance imaging (MRI)-based evaluation of adipose tissue (AT) might help to identify AT characteristics that predict AT loss. This study aimed to assess the impact of an 8-week low-calorie diet (LCD) on different AT depots and to identify predictors of short-term AT loss using MRI in adults with obesity.MethodsEighty-one adults with obesity (mean BMI 34.08 ± 2.75 kg/m², mean age 46.3 ± 10.97 years, 49 females) prospectively underwent baseline MRI (liver dome to femoral head) and anthropometric measurements (BMI, waist-to-hip-ratio, body fat), followed by a post-LCD-examination. Visceral and subcutaneous AT (VAT and SAT) volumes and AT fat fraction were extracted from the MRI data. Apparent lipid volumes based on MRI were calculated as approximation for the lipid contained in the AT. SAT and VAT volumes were subdivided into equidistant thirds along the craniocaudal axis and normalized by length of the segmentation. T-tests compared baseline and follow-up measurements and sex differences. Effect sizes on subdivided AT volumes were compared. Spearman Rank correlation explored associations between baseline parameters and AT loss. Multiple regression analysis identified baseline predictors for AT loss.ResultsFollowing the LCD, participants exhibited significant weight loss (11.61 ± 3.07 kg, p < 0.01) and reductions in all MRI-based AT parameters (p < 0.01). Absolute SAT loss exceeded VAT loss, while relative apparent lipid loss was higher in VAT (both p < 0.01). The lower abdominopelvic third showed the most significant SAT and VAT reduction. The predictor of most AT and apparent lipid losses was the normalized baseline SAT volume in the lower abdominopelvic third, with smaller volumes favoring greater AT loss (p < 0.01 for SAT and VAT loss and SAT apparent lipid volume loss).ConclusionsThe LCD primarily reduces lower abdominopelvic SAT and VAT. Furthermore, lower abdominopelvic SAT volume was detected as a potential predictor for short-term AT loss in persons with obesity.

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Obesity results in adipose tissue T cell exhaustion.

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