Supplementary Materials

The PDF file includes:

• Supplementary methods
• Fig. S1. HFD induces obesity in rats.
• Fig. S2. Enzymatic activity is enhanced in brains of rats fed a HFD.
• Fig. S3. Validation of ObR-specific labeling.
• Fig. S4. MMP-2 cleaves the extracellular domain of the ObR and impairs leptin-mediated signaling in the GT1-7 hypothalamic cell line.
• Fig. S5. Cleavage of the ObR extracellular domain is MMP-2–specific.
• Fig. S6. Identification of Mmp-2^−/− mice using gel zymography.
• Fig. S7. Confirmation of enhanced of Mmp-2 activity in the brain of mice fed a HFD by gel zymography with gelatin substrate.
• Fig. S8. Confirmation of MMP-2 shRNA and complementary DNA constructs.
• Fig. S9. Verification of mutated ObR functionality.
• Fig. S10. Summary diagram of HFD-induced extracellular leptin receptor cleavage by MMP-2 in the hypothalamus contributing to leptin resistance and weight gain.
• Table S1. List of primers used to detect induction of NF-κB target genes and Mmp-2.
• Legend for table S2.
• References (50–52)

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Other Supplementary Material for this manuscript includes the following:

• Table S2. Raw data (provided as a separate Excel file).