Consistent with previous studies that components of the LPS/CD14/TLR4 signaling cascade is required for metabolic inflammation and development of obesity [14], [15], we observed that, compared with WT mice, Myd88-deficient mice gained significantly less weight on the high-fat Western diet and possessed significantly lower epididymal fat pad and liver masses relative to total body weight (C. S. R. and F. B., unpublished data). Here, MYD88 is linked to obesity due to melanocortin 4 receptor deficiency.