Hormonal
Obesity induces a state of CD4 T-cell exhaustion and senescence in visceral adipose tissue (VAT), characterized by persistent PD-1 expression and restricted effector function, which creates a negative legacy that persists after weight loss and contributes to treatment resistance.
If you have a history of obesity, simply losing weight may not fully reset your immune system's behavior in fat tissue. This 'immune memory' can make you more prone to inflammation and weight regain. Strategies to manage this might focus on long-term immune health and reducing chronic inflammation, rather than just short-term weight loss, as the immune system in visceral fat may remain 'exhausted' or 'senescent' even at a lower weight.
When obesity persists, prolonged stimulation by leptin and circulating free fatty acids, repetitive antigen stimulation, activating stress responses, and hypoxia induce exhaustion of CD4 T cells in VAT... The obesity-associated transformation of CD4 T cells remains a negative legacy even after weight loss, causing treatment resistance of obesity-related conditions.
Why this rating
The paper is a review citing multiple primary studies (mice and humans) showing consistent findings on T-cell exhaustion and PD-1 upregulation in obesity.
Source
Drastic transformation of visceral adipose tissue and peripheral CD4 T cells in obesity
Kohsuke Shirakawa et al. · Frontiers in Immunology · 2023
DOI 10.3389/fimmu.2022.1044737
More from this paper
- Leptin acts as a key initiator of VAT inflammation by promoting the differentiation of CD4 T cells into Th1 and Th17 subsets and inducing T-cell exhaustion via STAT3 signaling and PD-1 expression.Good
- Adiponectin normally suppresses VAT T-cell inflammation by inhibiting T-cell proliferation and promoting apoptosis, but its levels are reduced in obesity, thereby releasing the 'brake' on inflammatory T-cell responses.Good
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