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PGC-1α-Coordinated Hypothalamic Antioxidant Defense Is Linked to SP1-LanCL1 Axis during High-Fat-Diet-Induced Obesity
Shuai Shi1,2, Jichen Wang1,2, Huan Gong1,2
1Laboratory of Experimental Animal Disease Model, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China.
Antioxidants (Basel, Switzerland)
|February 24, 2024
Summary
Impaired hypothalamic antioxidant defense worsens obesity. Enhancing this defense, via the PGC-1α-SP1-LanCL1 axis, can improve high-fat-diet-induced obesity and associated inflammation.
Area of Science:
- Neuroscience
- Metabolic Disorders
- Molecular Biology
Background:
- High-fat diet (HFD) consumption is linked to obesity, hypothalamic inflammation, and oxidative stress.
- The precise relationship between hypothalamic inflammation and oxidative stress in HFD-induced obesity remains unclear.
Purpose of the Study:
- To investigate the role of the antioxidant gene LanCL1 in the hypothalamus during HFD-induced obesity.
- To elucidate the molecular mechanisms linking hypothalamic oxidative stress and inflammation in obesity.
Main Methods:
- Utilized mouse models with targeted manipulation of the LanCL1 gene in the hypothalamus.
- Investigated the effects of short-term and long-term HFD exposure on hypothalamic gene expression and cellular pathways.
- Examined the interaction between peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), SP1, and LanCL1 in response to palmitic acid.
Main Results:
- Impaired hypothalamic antioxidant defense exacerbates HFD-induced inflammation and obesity.
- Elevated hypothalamic antioxidant defense improves HFD-induced inflammation and obesity.
- PGC-1α, in conjunction with SP1, regulates hypothalamic LanCL1 transcription in response to palmitic acid.
- Short-term HFD activates PGC-1α and LanCL1; long-term HFD leads to PGC-1α degradation and suppressed LanCL1 expression.
Conclusions:
- The hypothalamic PGC-1α-SP1-LanCL1 axis is crucial for regulating HFD-induced obesity.
- Findings highlight the intricate interplay between hypothalamic inflammation and oxidative stress in obesity development.
- Targeting this axis may offer therapeutic strategies for obesity and related metabolic disorders.
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