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Schematic of the proposed role of hypothalamic IKKβ/NF-κB and ER stress in obesity-related disease pathways. We propose that IKKβ/NF-κB connects with ER stress in the hypothalamus and translates overnutrition into central insulin and leptin resistance, leading to the development of obesity and T2D (solid arrows). We also further postulate that, as obesity and T2D progress, IKKβ/NF-κB participates in cumulative feedback loops (broken arrows).
