In contrast, Siah2 deficiency significantly reduced the number of adipocytes in the white fat (and trending down in the BAT) of the HFD-fed males, lending further support for sex-related differences in the role of Siah2 in regulating the relationship between fat mass expansion and adipose tissue inflammation with obesity in white and brown fat. Here, SIAH2 is linked to obesity due to melanocortin 4 receptor deficiency.