TNF and obesity due to melanocortin 4 receptor deficiency: Although metabolic diseases have been overwhelmingly associated with an inflammatory phenotype (11, 27, 29), our results suggest that hyperinsulinemia does not directly increase pro-inflammatory cytokine production (i.e., IL-6 and TNF-α) in the healthy heart, suggesting that other factors, such as obesity, play a pathogenic role during the inflammatory response.