TLR4 and serum lipopolysaccharide activity: To answer these foundational questions, we established a reductionist model that mimics IFN-I levels (recombinant IFN-β; a representative of IFN-Is) and/or increased endotoxemia (purified, TLR4 specific, LPS; mimic of endotoxemia) in an obese microenvironment (12).