Zinc Fingers Are Responsible for the Efficient Control of KLF7 on the Transcription of Genes in the NF-κB Signaling Pathway and Fatty Acid β-Oxidation

• • Wild-type KLF7 overexpression significantly increased NF-κB reporter activity in Ishikawa, HeLa, and EC109 cells (P < 0.05), whereas deletion of any single zinc finger (D1, D2, or D3) abolished this enhancement (P < 0.05), demonstrating that all three zinc fingers are required for inflammatory pathway activation. • • KLF7 did not alter NFKB1 mRNA (P > 0.05) or RelA (P65) protein levels in any cell line, indicating that its pro-inflammatory action occurs downstream of NFKB1 gene expression, which matters clinically because targeting KLF7 zinc fingers could modulate downstream cytokine production without disrupting core NF-κB component synthesis. • • Wild-type KLF7 significantly increased promoter activities of ACADL, ECH1, and HADHB (P < 0.05) in all three cell types, while zinc-finger-deficient mutants failed to do so, establishing that zinc fingers are essential for transcriptional control of fatty acid β-oxidation genes and highlighting a potential therapeutic vulnerability in metabolic disorders. • • Western blot analysis with ACTB as internal control confirmed that wild-type KLF7 elevated CPT1A, ACADL, and ECH1 protein expression, whereas zinc-finger deletions abrogated these increases, providing translational evidence that KLF7 zinc fingers are required for both transcriptional and protein-level regulation of β-oxidation, with implications for insulin resistance and obesity.