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Isolation, Characterization, and Purification of Macrophages from Tissues Affected by Obesity-related Inflammation
Published on: April 3, 2017
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Decreased Proteasomal Function Exacerbates Endoplasmic Reticulum Stress-Induced Chronic Inflammation in Obese Adipose
Shimpei Nakagawa1, Aya Fukui-Miyazaki2, Takuma Yoshida1
1Department of Pathology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
The American Journal of Pathology
|February 29, 2024
Summary
Impaired proteasome function increases endoplasmic reticulum (ER) stress, driving white adipose tissue (WAT) inflammation. This age-related decline may link to obesity in older adults.
Area of Science:
- Cellular Biology
- Aging Research
- Immunology
Background:
- Low-grade chronic inflammation is linked to aging and age-related diseases.
- Obesity-associated white adipose tissue (WAT) inflammation is exacerbated by aging.
- Molecular mechanisms of aging-related WAT inflammation are poorly understood.
Purpose of the Study:
- Investigate the impact of adipocyte senescence on WAT inflammation in a mouse model with reduced proteasomal function.
- Elucidate the role of proteasome impairment and endoplasmic reticulum (ER) stress in WAT inflammation.
Main Methods:
- Utilized transgenic mice with impaired proteasomal subunit β5t activity, exhibiting age-related phenotypes.
- Administered a high-fat diet to mice with proteasomal dysfunction.
- Analyzed WAT inflammation, macrophage infiltration, and adipocytokine expression.
- Investigated ER stress markers and adipocytokine induction in 3T3-L1 cells with impaired proteasomal activity.
Main Results:
- Proteasomal dysfunction and high-fat diet increased WAT inflammation and M1-like macrophage infiltration.
- Elevated levels of monocyte chemoattractant protein-1, plasminogen activator inhibitor-1, and tumor necrosis factor-α were observed.
- Impaired proteasomal activity activated ER stress pathways and induced proinflammatory adipocytokines in adipocytes.
Conclusions:
- Impaired proteasomal activity promotes WAT inflammation via ER stress and subsequent inflammatory pathways.
- Age-related decline in proteasomal function may contribute to obesity-related inflammation in elderly individuals.
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