Proposed mechanism for saturated fatty acid (SFA)-induced activation of inflammatory response in hypothalamus. Initially, SFA activates predominantly TLR4, engaging MyD88. The classical downstream signaling through IRAK/TRAF6/NFkB (not tested in the present study) leads to cytokine expression. Through a hitherto unknown mechanism, TLR4 activation induces ER stress, which boosts cytokine expression enhancing the inhibitory signals of anorexigenic hormone action.